Magellan Rx Report Summer 2020
Asthma: Current Guidelines and Treatment Options
Peanut Allergy: Advances in Treatment
Oncology Biosimilars: Landscape Update and Payer Considerations
Developing a Successful WeightManagement Program
Magellan Rx Report MEDICAL AND PHARMACY BENEFIT MANAGEMENT Summer 2020
Sickle Cell Disease:
Clinical and Management Update magellanrx.com
IN THIS ISSUE | Summer 2020
Managed Care Newsstand
Sickle Cell Disease:
Method Capability Spotlight:
Advances in Treatment
Current Guidelines and Treatment Options
Landscape Update and Payer Considerations
Published By Magellan Rx Management 15950 N. 76th St. Scottsdale, AZ 85260
Contributors Caroline Carney, M.D., M.Sc., FAPM, CPHQ
Tel: 401-344-1000 Fax: 401-619-5215
SVP, Market General Manager, MRx Specialty
magellanrx.com Editor Lindsay Speicher, J.D.
Project Manager, Magellan Method email@example.com 401-344-1105
Advertising, Sales and Distribution Carole Kallas firstname.lastname@example.org 401-344-1132
Clinical and Management Update
Health Economics and Outcomes Research
Developing a Successful WeightManagement Program
CMO, Magellan Rx Management
Steve Cutts, Pharm.D.
Haita Makanji, Pharm.D.
VP, Clinical Strategy and Innovation, Specialty
SVP, Sales and Business Development, Specialty
Yousaf Ali M.D., FACR
Chief, Division of Rheumatology, Mount Sinai West; Associate Professor of Medicine, Icahn School of Medicine at Mount Sinai
Steven L. D’Amato, B.S.Pharm.
Executive Director, New England Cancer Specialists
Joseph Mikhael M.D., M.Ed., FRCPC, FACP
Chief Medical Officer, International Myeloma Foundation
Natalie Tate, Pharm.D., MBA, BCPS Vice President, Pharmacy Management, BlueCross BlueShield of Tennessee
Steve Marciniak, R.Ph.
VP, Business Development, Magellan Method
Director II, Medical Benefit Drug Management, BlueCross BlueShield of Michigan
Stacy Inman, Pharm.D.
Saira A. Jan, M.S., Pharm.D.
Senior Clinical Project Manager
Director of Pharmacy Strategy and Clinical Integration, Horizon BlueCross BlueShield of New Jersey
Brian Kinsella, Esq. The content of Magellan RxTM Report — including text, graphics, images, and information obtained from third parties, licensors, and other material (“content”) — is for informational purposes only. The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Magellan RxTM Report does not verify any claims or other information appearing in any of the advertisements contained in the publication and cannot take responsibility for any losses or other damages incurred by readers in reliance on such content. Developed by D Custom.
Senior Legal Counsel
VP, External Communications
Director, External Communications
Editorial Advisory Board Mona M. Chitre, Pharm.D., CGP
Chief Pharmacy Officer & VP Clinical Analytics, Strategy & Innovation, Excellus BlueCross BlueShield
Dennis Bourdette M.D., FAAN, FANA
Chair and Roy and Eulalia Swank Family Research Professor, Department of Neurology, Oregon Health & Science University
A NOTE FROM OUR CMO
Dear Managed Care Colleagues, Welcome to our summer 2020 issue of the Magellan Rx Report! With so much disruption and uncertainty in 2020, Magellan Rx Management is committed to serving as a consistent and stable source by bringing our clients up-to-date reporting on managed care and clinical trends. Despite turbulence in the industry brought by COVID-19, we are bringing our readers the crucial news stories and highlighting exciting clinical advances and updates.
Other timely topics include asthma management (page 12) and Magellan Methodâ&#x20AC;&#x2122;s health and economics outcomes research capabilities (page 43). No issue of the Magellan Rx Report would be complete without our pipeline (page 51). To learn more about Magellan Rx Management and our support for payer initiatives of the future, please feel free to contact us at MagellanRxReport@magellanhealth.com. As always, we value any feedback you may have. I hope you enjoy the Report! Sincerely,
In our cover story (page 28), we update our readers on the current state of sickle cell disease treatment, focusing on associated challenges and delving into new and emerging therapies and the implications for managed care. Oncology biosimilars are changing the treatment and management landscape. On page 24, we explore payer considerations and strategies for effectively navigating and managing biosimilars. A peanut allergy treatment update (page 6), also focused around emerging therapies, highlights a Magellan Rx Management Clinical Connections webinar held earlier in 2020. We discuss the challenges of treating and managing peanut allergy, as well as both newly approved and pipeline treatments.
Caroline Carney, M.D., M.Sc., FAPM, CPHQ Chief Medical Officer Magellan Health & Magellan Rx Management
Continuing a Magellan Rx Report series on obesity management (see the first installment in our spring 2020 Report), we explore the process required to effectively develop an employer-sponsored weight-management program (page 39). An upcoming and final installment will focus on results from the implementation of such a program.
SUBSCRIBE TODAY! Stay on top of managed care trends and become a Magellan Rx Report subscriber. Email us at MagellanRxReport@magellanhealth.com to subscribe today. Magellan Rx Report provides pharmacy and medical management solutions for managed care executives and clinicians. We hope you enjoy the issue; thank you for reading.
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MANAGED CARE NEWSSTAND Senate Passes 3-Digit Suicide Prevention Hotline In May, the U.S. Senate passed legislation designating 9-8-8 as the new three-digit National Suicide Prevention Hotline. The House is expected to pass the bill sometime this summer. Congress initially passed legislation in 2018 to require the Federal Communications Commission (FCC) to study the creation of a hotline similar to the national 9-1-1 emergency hotline. The FCC approved a proposal in December 2019 along with various recommendations. This legislation allows states to collect fees to support operations of a national hotline and to expand existing capacity in their states. Estimated costs are $570 million for the first year and $175 million for the second year. The bill mandates that the Substance Abuse and Mental Health Services Administration (SAMHSA) facilitates training on addressing suicide prevention for LGBTQ youth, Native Americans, and people living in rural areas — populations of critical concern for suicide. The three-digit hotline will allow veterans to press “1” to access a specific hotline. An estimated 45,000 people die by suicide every year in the United States, including approximately 6,000 veterans. The hotline is directed to be in place a year following passage. The current national hotline, 1-800-273-TALK, will remain in place after the three-digit hotline is operational.
Coronavirus Emergency Relief Legislation Includes Temporary Increase in the Federal Medicaid Match Rate On March 18, Congress passed, and the president signed into law, the second emergency relief package dealing
4 | Magellan Rx Report | Summer 2020
with the coronavirus pandemic, which included a temporary increase in the Federal Medical Assistance Program (FMAP) match rate. The temporary increase of 6.2% for states began on Jan. 1 and goes until the end of the calendar quarter in which the public health emergency declared by the secretary of Health and Human Services is lifted. States are required to continue eligibility, or may expand eligibility, but they cannot restrict or remove Medicaid beneficiaries in the program as of March 18. States must also cover all coronavirus-related costs, including testing and treatment, and they may not impose any premiums, deductibles, or copays. The temporary increase does not apply to populations that are included in higher Medicaid match rates, such as Medicaid expansion populations under the Affordable Care Act, but rather only populations included in the ordinary Medicaid match rate. The House passed legislation in May to increase the FMAP rate to 14% beginning July 1 and ending June 30, 2021. The increased FMAP is designed to help support states and maintain insurance coverage within the Medicaid program as they deal with increased fiscal pressures resulting from the pandemic. The Senate has not acted on this bill.
Congress Passes Four Relief Packages Addressing the Pandemic and Is Expected to Pass a Fifth Package This Summer Through March and April, Congress passed sweeping legislation totaling $3 trillion to address the healthcare and economic challenges associated with the coronavirus pandemic. Four bills were passed and signed into law over an eight-week period, between March 6 and April 24. Provisions included critical funding for hospitals and providers, funding for testing supplies, two weeks of medical and family leave for people in companies with
less than 500 employees, $1,200 stimulus checks to individuals, a $600 federal add-on to weekly unemployment benefits, increased benefits for the food stamp program, and funds to provide school lunches while children were out of school. The legislation also created a paycheck protection program, providing grants and loans to small businesses to retain their employees during the crisis, as well as a program designed to assist large business, including the airlines. The four relief packages provided substantial funding for vaccine research, among countless other provisions. Congress is again considering a fifth package to address the fallout from the pandemic. The House passed a $3 trillion package to extend and expand many of these programs. The bill provided for nearly $1 trillion in aid to states and localities. It also would provide for a 100% subsidy for COBRA insurance for those who lose their jobs and would provide for a Special Enrollment Period (SEP) to sign up for health insurance coverage through the health exchanges. The package would also provide significant funding for increased testing and contact tracing. This legislation has ignited partisan differences, and the Senate has indicated that it would take a pause before devoting more funding to the crisis. This fifth package has been a focus of debate during the early part of the summer.
All States Began Some Form of Reopening by Memorial Day On April 16, the Trump administration announced a set of principles to reopen states and localities. The principles included that communities should be allowed to open through three phases. The states/localities should first show a 14day downward trajectory of cases. Testing and contact-tracing programs should also be robust in these areas. • In phase one, no more than 10 people
should congregate together, and social distancing should remain in place. Only essential travel should be allowed, and vulnerable populations should continue to shelter in place. • In phase two, groups of 50 or less would be allowed, and nonessential travel could resume. Vulnerable populations should continue to remain cautious. • In phase three, normal activity could resume, but people should limit time in crowded environments. In May, the Centers for Disease Control and Prevention (CDC) had initially developed a 60-page document detailing recommendations on reopening, but it was not released. Instead, more general one-page documents were released providing guidance on reopening the workplace, mass transit, childcare, schools, and restaurants and bars. Guidance for churches was initially held up. The recommendations contained general guidance, leaving it up to the states to determine processes for reopening various segments of society. All states had begun some sort of reopening by Memorial Day. Very few states had met the more stringent criteria first announced in April guidance as the Memorial Day weekend began.
Supreme Court to Hear Repeal of Affordable Care Act in the Fall The Supreme Court announced in March that it will again take up the issue of the Affordable Care Act’s constitutionality. This will be the third time that justices have heard cases dealing with the landmark 2010 law. Arguments are expected in the fall of 2020. In 2017, Congress struck down the individual mandate tax penalty in the tax bill passed that year. In a previous case, the justices ruled that the individual mandate was constitutional
under the taxation powers. The argument now before the Court is that without a tax penalty, the individual mandate is invalid, and therefore the entire law should now be struck down given its central place in the law. The case will likely ensure that the Affordable Care Act will be highly visible in this fall’s presidential campaign, along with other major issues such as Medicare for All, drug pricing, surprise medical billing, and healthcare issues associated with the coronavirus pandemic.
Many in Congress Call for Changes in the Medical and Drug Supply Chain The coronavirus pandemic highlighted weaknesses in the medical and drug supply chain, and Congress saw at least 10 bills introduced in the spring to try and address these issues. These bills range from creating incentives to bring manufacturing back to the United States to requiring the U.S. Food and Drug Administration (FDA) to improve drug tracking. Many called for studies to better understand vulnerabilities within the medical and drug supply chains. Drug shortages and the lack of medical equipment became critical issues early in the pandemic. It is expected that this will be a major policy issue for years to come.
Race for a Vaccine More than 100 research teams are working to find a vaccine for the coronavirus quickly, according to many media reports. Many experts believe it will take 12 to 18 months to develop a vaccine, but efforts are underway to shorten that time frame. As of Memorial Day, the U.S. Department of Health and Human Services (HHS) has awarded four contracts to the following companies in hopes of fast-tracking a vaccine: $1.2 billion to AstraZeneca for a phase three clinical
trial this summer, $483 million to Moderna, $500 million to Johnson & Johnson, and $30 million to Sanofi.
Telehealth The pandemic has moved telehealth forward in ways no one could have anticipated. Various federal and state regulatory actions, most of which are tied to emergency declarations, removed previous regulatory barriers. Many states have temporarily mandated equal payments through various administrative actions. Previously, providers had little financial incentive to offer telehealth visits because of the coverage and reimbursement gaps.
Supreme Court to Hear PBM Case On Jan. 10, the U.S. Supreme Court granted review of Rutledge v. Pharmaceutical Care Management Association (PCMA), meaning they will hear the case. In 2015, Arkansas enacted a “MAC/transparency” law that imposed onerous regulations on PBMs and their relationships with pharmacies. The PCMA filed suit challenging the Arkansas statute as preempted by the Employee Retirement Income Security Act of 1974 and Medicare Part D. The PCMA asked the Court to find the statute unconstitutional because it establishes requirements on PBMs that the state has no authority to establish and dictates terms of PBM contracts with ERISA plans and Medicare Part D plans. Both ERISA and Medicare Part D have very broad preemption provisions that limit states’ ability to enact laws impacting these areas of federal policy. The Supreme Court was originally anticipated to hold oral arguments April 27 and wrap up the case by June, but the Court’s schedule was disrupted by COVID-19. Oral arguments are now expected to occur next year.
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Peanut Allergy: Advances in Treatment Over the coming year, the peanut allergy space will likely transform from relying on strict avoidance as a long-term management option to introducing multiple available therapies. These advances will inevitably come with challenges to managing care.
Christopher Parrish, M.D., FAAAAI, FACAAI Assistant Professor of Pediatrics and Internal Medicine UT Southwestern Medical Center
Maryam Tabatabai, Pharm.D. Senior Director, Drug Information Magellan Health Services
An allergy is when the immune system reacts in a potentially harmful way to a normally harmless substance. In the U.S., 1 in 13 children has food allergies, and an estimated 40% of those with food allergies are allergic to more than one food.1 Peanut allergy is among the most common food allergies in the U.S., impacting 2.5% of children and 1.2% of the overall population.2, 3 Moreover, peanut allergy is the leading cause of food-allergy-related deaths in children.4 The prevalence of the allergy more than tripled from 1997 to 2008, and, according to a 2017 study, it has increased by 21% since 2010.5, 6 Thus, although the allergy resolves in an estimated 20% of children, it is conceivable that the number of adults living with the allergy will increase in the decades to come. After the publication of a landmark study showing that early introduction of peanut may reduce the risk of developing peanut allergy in high-risk infants,7 the National Institute of Allergy and Infectious Diseases (NIAID) published an addendum to its guidelines detailing when to introduce children to peanut-containing foods. The NIAID recommended adding peanut protein to the diet of infants with severe eczema, egg allergy, or both at age 4 to 6 months; of infants with mild to moderate eczema at 6 months; and of infants with none of those conditions at any time appropriate for the family.8 In 2019, the American Academy of Pediatrics updated its guidelines to recommend introducing allergenic foods, including peanut protein, into babiesâ&#x20AC;&#x2122; diets at as early as 4 to 6 months of age, in an effort to reduce the risk of developing food allergies.9 This is contrary to prior recommendations of avoiding allergens. Peanut is the food allergen most commonly associated with anaphylaxis, which occurs when the patient ingests the peanut protein.1 Symptoms of food allergy vary. Skin symptoms such as hives or swelling are most common. Anaphylaxis is a severe, potentially fatal, systemic (whole-body) reaction that may include skin symptoms and/or some combination of wheezing, shortness of breath, repetitive cough, throat swelling, vomiting, stomach cramps, diarrhea, dizziness, confusion, and other symptoms. According a 2012 survey, annual costs associated with food allergies in U.S. children totaled $24.8 billion, with $4.3 billion in direct medical costs.10 The majority of these medical costs are tied to emergency
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PEANUT ALLERGY | Continued
Figure 1. Incidence and Burden of Peanut Allergy
Figure 2. U.S. Peanut Allergy Statistics
Emergency department visits for food-induced anaphylaxis by allergen, per 100,000 children 8 Peanut
of kids in the U.S. have a peanut allergy
increase in cases since 2010
of peanut allergies resolve
Current Management and Treatment
Peanut allergy incidence % of total births
a controlled medical environment — may be necessary to clarify whether an individual is truly allergic or not.
department (ED) visits and inpatient hospitalizations resulting from anaphylaxis. Food allergies account for approximately 25% of anaphylaxis-related ED visits. Peanut and tree nut allergies are the most common cause of food-related anaphylaxis. In a 20072012 study, peanut allergies were responsible for 37% of foodinduced anaphylaxis cases and 35% of hospital admissions due to anaphylaxis.11
Diagnosis As with other food allergies, diagnosing peanut allergy can be a complicated process, considering the variance in symptoms from patient to patient and from reaction to reaction. Typically, an allergist will be able to identify the culprit food by taking a detailed history of food eaten in the minutes to hours preceding symptom onset. Skin and blood tests are used to confirm the diagnosis. In uncertain cases, an oral food challenge — in which the patient will be fed increasing amounts of peanut protein over time while in
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There is no cure for peanut allergy. Current treatment options for peanut allergy include avoidance, education and label reading, recognition of a reaction, and administration of emergency epinephrine in the event of a severe reaction after accidental exposure. Due to the severe nature of many peanut allergy cases, the condition is typically managed by strict avoidance of peanuts and any product that contains peanut protein. The results of such avoidance strategies are variable. Strict avoidance can present numerous challenges to those with peanut allergy and their families, including substantial burdens on quality of life and activities.12 Despite peanut-free schools, there are continued challenges with unintended exposure. Those with peanut allergies have reported limiting travel — specifically air travel — and experiencing difficulty dining out due to fear
Current treatment options for peanut allergy include avoidance, education and label reading, recognition of a reaction, and administration of emergency epinephrine in the event of a severe reaction after accidental exposure.
of exposure. Additionally, label reading can often be ineffective, due to potential cross-contamination in product manufacturing and packaging. Therefore, strict avoidance not only burdens those with peanut allergy but can also sometimes be ineffective in preventing severe allergic reactions and anaphylaxis.
Emerging Therapies Palforzia™ On Jan. 31, the U.S. Food and Drug Administration (FDA) approved Palforzia™ (peanut (Arachis hypogaea) allergen powder-dnfp) (called AR101 prior to approval), an oral immunotherapy indicated for the mitigation of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut in patients with peanut allergy.13 Palforzia™ is approved for initiation of treatment in peanut-allergic patients ages 4 through 17. This immunotherapy is formulated to require phased-dose escalation over a period of time followed by ongoing maintenance at a dose of 300 mg, which is approximately equivalent to the protein content of a single peanut kernel.13 The first several doses (initial dose escalation) and each subsequent dose escalation of oral Palforzia™ are conducted under supervision by a healthcare professional in a certified healthcare setting. In the pivotal PALISADE trial, 496 patients ages 4 to 17 with peanut allergy participated with a primary endpoint of ingesting a single dose of at least 600 mg of peanut protein (cumulative dose of 1043 mg) after six months of maintenance treatment, without dose-limiting symptoms at the exit food challenges.14
» 67.2% of patients receiving AR101 were able to tolerate >600 mg of peanut protein (cumulative 1043 mg), compared to 4% of those receiving placebo (primary endpoint). » 76.6% of patients receiving AR101 tolerated a single dose of 300 mg of peanut protein (cumulative 443 mg), compared to 8.1% of those receiving placebo (p<0.0001). » 50.3% of patients receiving AR101 tolerated 1,000 mg of peanut protein (cumulative 2043 mg) without dose-limiting effects, compared to 2.4% of placebo patients (p<0.0001). » At each dose level, the maximum severity of symptoms was lower for patients receiving AR101 than for those receiving placebo. » Over 95% of patients total experienced some adverse event, mostly categorized as mild to moderate. » During the trial, excluding the food challenges, 14% of patients on AR101 received epinephrine, compared with 6.5% of patients receiving placebo. » 11.6% of patients receiving AR101 dropped out due to adverse events. Notably, the most common adverse events experienced were nausea, vomiting, and throat itching. » Efficacy was not shown in patients >18 years of age. While Palforzia™ has been shown to help reduce the severity of allergic reactions that may occur with peanut exposure, patients still must maintain a strict peanut-free diet while on the treatment regimen.14 Palforzia™ is only available through a restricted Risk Evaluation and Mitigation Strategies (REMS) program; patients as well as prescribers, pharmacies, and healthcare facilities involved the treatment plan must be enrolled.
Viaskin® Peanut Currently under FDA review, the Viaskin® Peanut patch from DBV Technologies is an epicutaneous immunotherapy targeting peanut allergy in pediatric patients.15 Viaskin® delivers very small amounts of peanut protein via a patch worn on intact skin to induce desensitization over time. PEPITES Results:15 The trial tested 238 pediatric patients who were administered Viaskin® Peanut patch containing 250 mcg of peanut protein (equivalent to approximately 1/1000th of one peanut kernel) daily over 12 months. Patients receiving Viaskin® had a 35.3% responder rate, compared with patients receiving placebo, who had a 13.6% responder rate.16
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PEANUT ALLERGY | Continued
DR. CHRISTOPHER PARRISH Allergist Immunologist Specialist
Cracking Peanut Allergies magellanrx.com/watch
BARBARA CORN Vice President, MRx Navigate Secretary, Asthma & Allergy Foundation, St. Louis Chapter
The prespecified lower bound of confidence interval threshold was not met. A total of 89.9% of patients completed the trial, and adherence rates of 98.5% were reported.
In May, the Institute for Clinical and Economic Review (ICER) conducted a review of AR101, Viaskin® Peanut, and oral immunotherapy (OIT).20 • Clinical effectiveness: The review concluded that highcertainty evidence demonstrates that OIT increases allergic and anaphylactic reactions for at least the first year of treatment despite effective desensitization, without evidence of longterm benefits. • Long-term cost-effectiveness: The economic model estimated incremental cost-effectiveness ratios for AR101 and Viaskin® Peanut as follows: ◦ AR101: $88,000 (95% credible range (CR) = $52,000$195,000) per quality-adjusted life-year (QALY) ◦ Viaskin® Peanut: $216,000 (95% CR = $126,000-$491,000) per QALY The ICER review also provided several key policy recommendations, including the following:20
More recent trial results showed that after 36 months of treatment, 51.8% of patients reacted at an eliciting dose of >1000 mg of peanut protein, compared to 40.4% after 12 months. The most common treatment-emergent adverse events were mild to moderate skin reactions localized at the administration site.
• Prescription of peanut-desensitization therapies should be restricted to allergists and immunology specialists, or, where there is inadequate access to allergists, to primary care physicians in consultation with a specialist. • Payers may consider limiting coverage for initiation of desensitization treatment to patients between ages 4 and 17 who represent the population studied to date. • Payers should not stop coverage at age 18 for patients who have been on continuous desensitization therapy.
Biologics and Alternative Treatments on the Horizon
Biologics indicated for allergic diseases such as asthma and severe eczema are currently being studied for peanut allergy. Roche’s Xolair® (omalizumab), an FDA-approved biologic indicated for asthma and chronic idiopathic urticaria, is currently in a phase three trial assessing its effectiveness as a monotherapy or adjunct therapy in combination with an oral immunotherapy in both children and adults with peanut allergy.18 Regeneron Pharmaceuticals’ Dupixent® (dupilumab), an FDA-approved biologic indicated for asthma, severe eczema, and nasal polyps, is currently in a phase two trial evaluating the efficacy of dupilumab as a monotherapy in pediatric patients with peanut allergy.19 While more research must be done here, these biologics could present another treatment option for those living with peanut allergy. Alternative avenues of therapeutics are in earlier stages of research as well.
Over the coming year, the peanut allergy space has the potential to be transformed from relying on strict avoidance as the sole longterm management option to introducing multiple available therapies. Currently, patients must continue to maintain a strict peanutfree diet, including while on a treatment regimen, and carry injectable epinephrine. Advances in peanut allergy treatment may present opportunities for improved quality of life for patients and their families, but not without challenges in managing care. Still, some unknowns remain in the allergy treatment space. While immunotherapies have the potential to positively impact quality of life, data have not yet been reported to confirm this impact. Additionally, sustained unresponsiveness to peanut allergens after stopping long-term use of immunotherapy has proven elusive. The nature of peanut allergy and the immunotherapies introduced require close healthcare supervision, monitoring, and care.
PEPITES Follow-Up Results:16
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Continual daily dosing of immunotherapy, which can be costly, is crucial for continued desensitization. The short-term financial burden of increased healthcare resource utilization — from provider hours and prolonged visits in healthcare facilities to dose escalations possibly requiring multiple prescriptions over the course of
treatment — must be taken into consideration when developing management plans and determining the patients who will most benefit from treatment regimen. Solid criteria may be explored to ensure access is available for appropriate patients.
“Peanut Allergy.” American College of Allergy, Asthma, and Immunology, 2019, https://acaai.org/allergies/types/food-allergies/ types-food-allergy/peanut-allergy.
11. Parlaman, Joshua et al. “Emergency and Hospital Care for FoodRelated Anaphylaxis in Children.” Hospital Pediatrics, May 2016, https://doi.org/10.1542/hpeds.2015-0153.
Sicherer, Scott et al. “Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit dial telephone survey: A 5-year follow-up study.” The Journal of Allergy and Clinical Immunology, Dec. 1, 2003, https://doi.org/10.1016/S00916749(03)02026-8.
12. Parrish, Christopher. “Management of Peanut Allergy: A Focus on Novel Immunotherapies.” American Journal of Managed Care, Oct. 19, 2018, https://www.ajmc.com/journals/supplement/2018/managedcare-perspective-peanut-allergy/management-of-peanut-allergy-afocus-on-novel-immunotherapies.
Gupta, R. et al. “OR078 The prevalence of childhood food allergy in the United States: an update.” American College of Allergy, Asthma & Immunology Annual Scientific Meeting, Oct. 26-30, 2017, https://doi. org/10.1016/j.anai.2017.08.060.
13. “Palforzia.” U.S. Food and Drug Administration, Feb. 24, 2020, https:// www.fda.gov/vaccines-blood-biologics/allergenics/palforzia.
Cannon, H. Eric. “The Economic Impact of Peanut Allergies.” American Journal of Managed Care, Oct. 19, 2018, https://www.ajmc.com/ journals/supplement/2018/managed-care-perspective-peanutallergy/the-economic-impact-of-peanut-allergies.
Sicherer, Scott et al. “Prevalence of peanut and tree nut allergy in the US determined by a random digit dial telephone survey.” The Journal of Allergy and Clinical Immunology, April 1999, https://doi. org/10.1016/s0091-6749(99)70224-1.
Sicherer, Scott et al. “US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up.” The Journal of Allergy and Clinical Immunology, May 12, 2010, https://doi.org/10.1016/j. jaci.2010.03.029.
Du Toit, George et al. “Randomized trial of peanut consumption in infants at risk for peanut allergy.” The New England Journal of Medicine, Feb. 26, 2015, https://www.nejm.org/doi/full/10.1056/ NEJMoa1414850. Togias, Alkis et al. “Addendum Guidelines for the Prevention of Peanut Allergy in the United States: Report of the NIAID-Sponsored Expert Panel.” National Institute of Allergy and Infectious Diseases, 2016, https://www.niaid.nih.gov/sites/default/files/addendumpeanut-allergy-prevention-guidelines.pdf. Greer, Frank et al. “The Effects of Early Nutritional Intervention on the Development of Atopic Disease in Infants and Children: The Role of Maternal Dietary Restriction, Breastfeeding, Hydrolyzed Formulas, and Timing of Introduction of Allergenic Complementary Foods.” Pediatrics, April 2019, https://doi.org/10.1542/peds.2019-0281.
14. The PALISADE Group of Clinical Investigators. “AR101 Oral Immunotherapy for Peanut Allergy.” The New England Journal of Medicine, Nov. 22, 2018, https://doi.org/10.1056/NEJMoa1812856. 15. “DBV Aims to Unlock the Powerful Immune Properties of the Skin.” DBV Technologies, 2020, https://www.dbv-technologies.com/viaskinplatform/. 16. Fleischer, David et al. “Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion Among Children With Peanut Allergy: The PEPITES Randomized Clinical Trial.” Journal of the American Medical Association, Feb. 22, 2019, https://doi. org/10.1001/jama.2019.1113. 17. Fleischer, David et al. “Open-Label Follow-Up of the PEPITES Study (PEOPLE) to Evaluate the Long-Term Efficacy and Safety of Epicutaneous Peanut Immunotherapy in Peanut-Allergic Children.” The Journal of Allergy and Clinical Immunology, Feb. 1, 2020, https:// doi.org/10.1016/j/jaci.2019.12.453. 18. Omalizumab as Monotherapy and as Adjunct Therapy to MultiAllergen OIT in Food Allergic Participants (OUtMATCH). U.S. National Library of Medicine, Jan. 18, 2020, https://clinicaltrials.gov/ct2/show/ NCT03881696. 19. Study to Evaluate Dupilumab Monotherapy in Pediatric Patients With Peanut Allergy. U.S. National Library of Medicine, Feb. 13, 2020, https://clinicaltrials.gov/ct2/show/NCT03793608. 20. Tice, Jeffrey et al. “The effectiveness and value of oral immunotherapy and Viaskin Peanut for peanut allergy.” Journal of Managed Care and Specialty Pharmacy, May 2020, https://www.jmcp. org/doi/full/10.18553/jmcp.2020.26.5.620?mobileUi=0.
10. Gupta, Ruchi et al. “The Economic Impact of Childhood Food Allergy in the United States.” JAMA Pediatrics, November 2013, https://doi. org/10.1001/jamapediatrics.2013.2376.
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Asthma Update: Current Guidelines and Treatment Options The introduction of biologics has opened a new route of administration for treating asthma, including the possibility of self-administration. Asthma is a chronic disease of the lungs that affects adults and children of all ages and is characterized by repeated episodes of wheezing, breathlessness, chest tightness, and nighttime or early morning coughing. The cause is unknown, and the condition currently has no cure. Symptoms are managed by reduced exposure to triggers, acute treatment of exacerbations, and prevention of future attacks. Without proper management, asthma can result in absences from work or school, frequent emergency department (ED) visits, hospitalizations, and premature death.1
Mona Chitre, Pharm.D., CGP Chief Pharmacy Officer & VP, Clinical Analytics, Strategy and Innovation Excellus BlueCross BlueShield
Asthma affects 25 million people, including 6 million children. In 2016, 1.8 million people visited an ED for asthma-related symptoms, resulting in 189,000 individuals being hospitalized.2 Adult self-reported asthma prevalence varies by state, ranging from 7.3% in Texas to 13.2% in New Hampshire (Figure 1).2 Asthma and asthma-related symptoms create a significant financial burden, contributing to $50.3 billion in medical costs for one year, with additional indirect costs of $3 billion due to missed work and school and $29 billion due to asthma-related mortality.3
Figure 1. Prevalence Rates by State
<8.1% 8.1%-<8.8% 8.8%-<9.5% 9.5%-<9.9% 9.9%+
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Table 1. Asthma Classifications4 Asthma management should include a controller medication, a rescue medication, and, in cases of severe asthma, an add-on therapy. Classifications of asthma severity are as follows:
Frequency of symptoms
≤2 days per week
>2 days per week but not daily
Throughout the day
Frequency of nighttime awakenings
≤2 times per month
3 to 4 times per month
>1 time per week but not nightly
Frequency of short-acting inhaler use
≤2 days per week
>2 days per week but not daily and not more than once per day
Several times per day
Table 2. Asthma Control4 Controlling asthma to reduce exacerbations is the goal for all patients. Control can be interpreted differently depending on a patient’s triggers and asthma symptoms. Below are the standards for what control should look like for all patients:
Components of Control Interference with normal Symptoms activities
Well-Controlled None <2 days per week
Very Poorly Controlled
2 days per week Some limitations Minor limitations
Throughout the day limited Extremely
<2 times per month
1-3 times per week
>4 times per week
Interference with normal activity
<2 days per week
>2 days per week
Several times per day
FEV1 or peak flow
>80% predicted/personal best
60-80% predicted/personal best
<60% predicted/personal best
Global Initiative for Asthma: Current Guidelines and Recent Updates The long-term goals of asthma management are to achieve symptom control; maintain normal activity levels; and minimize the risk of asthma-related death, exacerbations, persistent airflow limitation, and side effects. Effective management requires a partnership between the patient — or, where appropriate, the parent or caregiver — and the healthcare professional managing their treatment plan. Communication of symptoms, triggers, and barriers to treatment must be discussed openly to maximize benefit. Effective communication on the part of the provider can be invaluable in assessing the health literacy of the patient and/or parent/caregiver and can increase the success of the treatment plan.
Making Decisions About Asthma Treatment Control-based management of asthma should take place in a continuous cycle of assessment, treatment, and review of the patient’s response. This assessment should include both the level of symptom control and the future risk of exacerbation and side effects. Treatment decisions should also take into consideration the patient’s inhaler technique, adherence, and cost to the patient. Other considerations are discussed and tabulated in Tables 1, 2, and 3.
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ASTHMA UPDATE | Continued
Table 3. Recommendations4 If reported or observed symptoms indicate a need for changes in therapy, step therapy should be considered. Step therapy and the timeline associated with implementing and assessing a successful change are summarized below:
Recommended Action for Treatment
• Maintain current step • Regular follow-up for 1-6 months • Consider step down if well-controlled for at least 3 months
• Step up 1 step • Reevaluate in 2-6 weeks • Consider alternative therapies for adverse reactions
Very Poorly Controlled
• • • •
Consider short course of oral corticosteroids Step up 1-2 steps Reevaluate in 2 weeks Consider alternative therapies for adverse reactions
Inhaled Corticosteroids (ICS)
The current landscape for treating asthma includes several products within multiple classes, each of which has variations in mechanism of action and duration of therapy.
Depending on the severity of their condition, most asthma patients will also be prescribed an inhaled corticosteroid (ICS) for as-needed or daily use. Treatment with daily low-dose ICS is highly effective in reducing asthma symptoms and the risk of asthmarelated exacerbations, hospitalization, and death.4 Adults and adolescents with mild asthma should be treated with as-needed low-dose ICS-formoterol to reduce risk of severe exacerbations.
Short-Acting Beta Agonists (SABA) Most, if not all, asthma patients are prescribed a rescue inhaler for acute symptoms, often a short-acting beta agonist (SABA). All patients should be taught to use a SABA as a rescue inhaler for exacerbations. Because of the likelihood for patients to become reliant on SABA treatment and the side effects associated with overuse, the Global Initiative for Asthma (GINA) no longer recommends treatment with a SABA alone. » Use: These rescue inhalers should be used during an asthma attack or before exercise, as directed. » How they work: They relax the smooth muscle in the lungs that constricts and makes it difficult to breathe during an asthma attack. They do not help to reduce the frequency of asthma attacks and should be used only as needed. » Common side effects include: fast heartbeat or palpitations, headache, and tremors » Available products include: albuterol and levalbuterol
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» U se: These maintenance inhalers are meant to be used daily to reduce the risk of asthma attacks and improve lung function. » How they work: They reduce both inflammation and the body’s immune response to allergens. Unlike oral corticosteroids, these medications are inhaled directly into the lungs, thus carrying a lower risk of systemic side effects. It is important to rinse your mouth with water and spit it out after each use of the inhaler to avoid the risk of an infection called thrush. Daily adherence to these medications is very important in order for them to work best. » Common side effects include: headache, thrush, nausea, sore throat, runny nose, and hoarseness » Available products include: beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, mometasone, and triamcinolone
If a patient’s asthma remains uncontrolled despite adherence and proper inhaler technique, additional steps and medications may be prescribed. The following additional classes of medications are available to treat asthma symptoms.
Anticholinergic Agents » Use: Short-acting agents such as ipratropium can be used to treat symptoms of shortness of breath and wheezing, while longeracting medications such as tiotropium are used to prevent asthma attacks. » How they work: These medications also relax the smooth muscle in the lungs that constricts during an asthma attack. Many medications in this class are approved to treat Chronic Obstructive Pulmonary Disease (COPD), another lung condition, but are not approved to treat asthma. » Common side effects include: dry mouth, urinary retention, and worsening of narrow-angle glaucoma » Available products include: ipratropium and tiotropium
Leukotriene-Modifying Agents » Use: These medications are taken orally to reduce the risk of having an asthma attack. » How they work: They block the activity of a specific cell involved in the body’s immune response to allergens that can lead to airway swelling and smooth-muscle constriction. » Common side effects include: cough, headache, sore throat, and runny nose » Available products include: montelukast, zafirlukast, and zileuton
Long-Acting Beta Agonists (LABA) » Use: They should always be prescribed in combination with an inhaled corticosteroid when being used to treat asthma. Monotherapy with long-acting beta agonists may increase the risk of side effects but when used with inhaled corticosteroids can help achieve better asthma control than inhaled corticosteroids can alone. » How they work: These medications work similarly to shortacting beta agonists in that they promote bronchodilation but provide a longer response. » Common side effects include: headache, nasal congestion, sore throat, runny nose, and bronchitis » Available products include: salmeterol, formoterol, and vilanterol
Xanthine Derivatives » How they work: These medications relax smooth muscle in the airways and reduce inflammation. » Common side effects include: headache, insomnia, nausea, and vomiting » Available products include: theophylline
Mast Cell Stabilizers » How they work: These medications bind to a cell involved in the immune system response to block the release of histamine, a chemical involved in allergic reactions. » Common side effects include: throat irritation, bad taste, coughing, wheezing, and nausea » Available products include: cromolyn
Oral Corticosteroids » Use: Treatment should be reserved for severe asthma and should be used for as short a time as possible to reduce the risk of systemic side effects. » How they work: This class of medications works similarly to inhaled corticosteroids in reducing inflammation and the body’s immune system response to allergens; however, they are taken orally and can therefore affect the whole body, not just the lungs. » Common side effects include: fluid retention, alteration in glucose tolerance, high blood pressure, mood changes, increased appetite, and weight gain » Available products include: prednisone, methylprednisolone, dexamethasone, hydrocortisone, cortisone, and prednisolone
Biologics » Use: These medications are injected under the skin by a healthcare professional or by the patient and are administered generally every two, four, or eight weeks. They are used in severe asthma that is not well controlled by inhaled corticosteroids or if patients have asthma that is associated with allergies and a type of immune cell known as an eosinophil. » How they work: They are all antibodies that target specific cell types in the body’s immune system to block the inflammatory response that occurs in asthma. » Common side effects include: fatigue, pain, and injection-site reaction » Available biologics include: omalizumab, reslizumab, benralizumab, mepolizumab, and dupilumab
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ASTHMA UPDATE | Continued
Treatment should be customized for the patient’s symptoms, lifestyle, and ability to use different devices to administer medicine.
Treatment should be customized for the patient’s symptoms, lifestyle, and ability to use different devices to administer medicine; Patients with hand-eye coordination and/or dexterity issues may need tools to help with administration of their therapy. Treatment plans should also include assessment of inhaler technique, adherence with the chosen therapy, and cost to the patient. Changes to therapy should be driven by symptoms patients are having while using their prescribed asthma treatment regimen or by results of spirometry testing. See Figures 2 and 3 for step therapy recommendations.
Figure 2. Personalized Management for Adults and Adolescents (12+ Years): Control Symptoms and Minimize Future Risk5 Confirm diagnosis if necessary Control symptoms and modifiable risk factors (including lung function) Comorbidities Inhaler technique and adherence Patient goals
Personalized asthma management: Access, adjust, review response Symptoms Exacerbations Side effects Lung function Patient satisfaction
Treat modifiable risk factors and comorbidities Nonpharmacological strategies Education and skills training Asthma medications
Asthma medication options: Adjust treatment up and down for individual patient needs
PREFERRED CONTROLLER to prevent exacerbations and control symptoms Other controller option
STEP 4 STEP 3
STEP 1 As-needed low-dose ICS-formoterol* Low-dose ICS taken whenever SABA is taken†
Daily low-dose inhaled corticosteroid (ICS) or as-needed low-dose ICS-formoterol*
Leukotriene receptor antagonist (LTRA) or low-dose ICS taken whenever SABA taken†
As-needed low-dose ICS-formoterol*
Other reliever option
Medium-dose ICS or low-dose ICS+LTRA#
Refer for phenotypic assessment± add-on therapy, e.g., tiotropium, anti-lgE, anti-IL5/5R, anti-IL4R
High-dose ICS, add-on liotropium or LTRA#
Add low-dose OCS, but consider side effects
As-needed low-dose ICS-formoterol for patients prescribed maintenance and reliever therapy‡
As-needed short-acting β2-agonist (SABA)
*Off-label; data only with budesonide-formoterol (bud-form) †Off-label; separate or combination ICS and SABA inhalers ‡Low-dose ICS-form is the reliever for patients prescribed bud-form or BDP-form maintenance and reliever therapy #Consider adding HDM SLIT for sensitized patients with allergist rhinitis and FEV1>70% predicted
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STEP 5 High-dose ICS-LABA
Figure 3. Personalized Management for Children (6-11 Years): Control Symptoms and Minimize Future Risk5
Confirm diagnosis if necessary Control symptoms and modifiable risk factors (including lung function) Comorbidities Inhaler technique and adherence Child and parent goals
Personalized asthma management: Access, adjust, review response
Asthma medication options:
Symptoms Exacerbations Side effects Lung function Child and parent satisfaction
Treat modifiable risk factors and comorbidities Nonpharmacological strategies Education and skills training Asthma medications
Adjust treatment up and down for individual child’s needs
STEP 4 STEP 3 PREFERRED CONTROLLER to prevent exacerbations and control symptoms Other controller option
STEP 2 Daily low-dose inhaled corticosteroid (ICS) (see table of ICS dose ranges for children)
Low-dose ICS Leukotriene receptor antagonist (LTRA) or taken whenever low-dose ICS taken whenever SABA taken* SABA taken* or daily low-dose ICS
STEP 5 Refer for phenotypic assessment± add-on therapy, e.g. anti-lgE
Low-dose ICS-LABA or medium-dose ICS
High-dose ICS-LABA or add-on triotropium or LTRA#
Add-on anti-IL5 or low-dose OCS, but consider side-effects
As-needed short-acting β2-agonist (SABA) *Off-label; separate ICS and SABA inhalers; only one study in children
Other treatment modalities can be leveraged for patients not responding to standard-of-care therapies mentioned above. These can include allergen immunotherapy, subcutaneous immunotherapy, sublingual immunotherapy, and bronchial thermoplasty.5 Additional add-on considerations for people with asthma include vitamin D supplementation and the influenza vaccine, as asthmatic patients have an increased risk of contracting the flu. Nonpharmacologic interventions to consider include limiting exposure to secondhand smoke, smoking cessation for known smokers, avoiding occupational exposure to sensitizing agents, weight reduction (if
appropriate), breathing exercises, a healthy diet including fruits and vegetables, and physical activity as tolerated.
Cost of Treatment Cost and coverage are important considerations for both the payer and the patient when changing or adding to a patient’s asthma regimen. The cost of asthma treatment varies based on route of administration and therapeutic class. Table 4 shows the current costs for asthma medications.
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ASTHMA UPDATE | Continued
Table 4. Current Asthma Treatments and Associated Whole Acquisition Cost (WAC) per Month6
Route of Administration
Mechanism of Action
Wholesale Acquisition Cost (WAC) per Month
Corticosteroid; long-acting beta-2 adrenoreceptor agonist (LABA)
Powder inhalation (0.1 mg/INH, 0.05 mg/INH; 0.25 mg/INH, 0.05 mg/ INH; 0.5 mg/INH, 0.05 mg/INH)
Aerosol, metered inhalation (0.045 mg/INH, 0.021 mg/INH; 0.115 mg/ INH, 0.021 mg/INH; 0.23 mg/INH, 0.021 mg/INH)
Powder inhalation (0.055 mg/INH, 0.014 mg/INH; 0.113 mg/INH, 0.014 mg/ INH; 0.232 mg/INH, 0.014 mg/INH)
fluticasone propionate; salmeterol xinafoate
fluticasone propionate; salmeterol xinafoate
fluticasone propionate; salmeterol
fluticasone furoate; vilanterol trifenatate
Powder inhalation (0.1 mg/INH, 0.025 mg/INH; 0.2 mg/INH, 0.025 mg/ INH)
Interleukin 5 (IL-5) antagonist
Single-use vial (10 mg/ mL)
formoterol fumarate; mometasone furoate
Merck & Co.
Aerosol, metered inhalation (0.005 mg/INH, 0.1 mg/INH; 0.005 mg/ INH, 0.2 mg/INH)
Subcutaneous injection every other week after loading dose
Regeneron; Sanofi Genzyme
Interleukin 4 receptor (IL4R) antagonist; interleukin 13 receptor (IL-13R) antagonist
MedImmune; AstraZeneca; Kyowa Hakko Kirin
Interleukin 5 receptor (IL-5R) antagonist
30 mg/mL solution in a single-dose prefilled syringe
MedImmune; AstraZeneca; Kyowa Hakko Kirin
100 mg of lyophilized powder in a single-dose vial for reconstitution
prednisolone sodium phosphate
Tablet, orally disintegrating (10 mg; 15 mg; 30 mg)
10 mg $950.40 15 mg $1,235.37 30 mg $1,577.28
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Table 4. Current Asthma Treatments and Associated Whole Acquisition Cost (WAC) per Month6 (cont.)
Route of Administration
Mechanism of Action
Wholesale Acquisition Cost (WAC) per Month
beclomethasone dipropionate HFA
Teva; Norton (Waterford)
Aerosol, metered inhalation (0.04 mg/IH, 0.08 mg/INH)
0.04 mg/INH $190.21; 0.08 mg/INH $254.68
Rayos (1 mg)
Tablet, delayed-release oral (1 mg; 2 mg; 5 mg)
Powder inhalation (0.05 mg/INH)
Singulair (chewable tablets)
Merck & Co.
Leukotriene receptor antagonist
Tablet, chewable oral (4 mg; 5 mg)
Singulair (oral granules)
Merck & Co.
Leukotriene receptor antagonist
Granule oral (4 mg/packet)
Merck & Co.
Leukotriene receptor antagonist
Tablet oral (10 mg)
tiotropium bromide monohydrate
Long-acting muscarinic antagonist (LAMA)
Spray, metered inhalation (0.00125 mg/INH, 0.0025 mg/INH)
budesonide; formoterol fumarate dihydrate
Aerosol, metered inhalation (0.16 mg/INH, 0.0045 mg/INH)
budesonide; formoterol fumarate dihydrate
Aerosol, metered inhalation (0.08 mg/INH, 0.0045 mg/INH)
Roche; Novartis; Genentech
Subcutaneous (150 mg/ vial; 75 mg/0.5 mL PFS; 150 mg/1 mL PFS)
150 mg/1 mL $1,128.48; 75 mg/0.5 mL $564.24
*The recommended dose of Fasenra® is 30 mg administered once every four weeks for the first three doses and then once every eight weeks thereafter.7 **Cost listed is by unit; multiple vials are needed to achieve dosing of 75 to 375 mg every two or four weeks.8
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ASTHMA UPDATE | Continued
Whatâ&#x20AC;&#x2122;s on the Horizon: Pipeline for Asthma The pipeline for asthma includes the possibility of additional combinations of inhaled products, oral agents, and injectable biologics. Table 5 shows emerging asthma therapies expected in the near future.
Table 5. Current Asthma Treatment Pipeline9 Pipeline Drug Name
Rottapharm | Madaus
Calcium-activated potassium channel activator
APC-1000 (505(b)(2) of QVAR 80)
beclometasone dipropionate; formoterol fumarate dihydrate
Receptor tyrosine kinase inhibitor
albuterol sulfate; budesonide
Avillion; AstraZeneca; Pearl Therapeutics
budesonide; glycopyrrolate; formoterol fumarate
Corticosteroid; LABA; LAMA
indacaterol maleate; mometasone furoate
indacaterol maleate; mometasone furoate; glycopyrronium bromide
Corticosteroid; LABA; LAMA
fluticasone furoate; umeclidinium bromide; vilanterol trifenatate
Corticosteroid; LABA; LAMA
Mechanism of Action
Payer Considerations The addition of biologic anti-IL 4 receptor antagonists to the list of potential treatment options for asthma has introduced a new route of administration to the landscape. The cost of these medica-
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tions varies depending on how often they are dosed and whether a loading dose needs to be given when initiating therapy. Four of the five biologics are administered subcutaneously; two, dupilumab
and benralizumab, can be self-administered once the patient is trained by a healthcare professional. The option of self-administration can eliminate site-of-service coverage for this class. Patients will still need to step through inhaled and oral therapies before the addition of a biologic as they are approved as adjunct therapy. The addition of a biologic agent to a patient’s therapy should be looked at by payers through their policy to ensure proper prescribing. There are five biologic therapies that can be used as adjunct therapy to treat severe asthma not adequately controlled with inhaled corticosteroids: • • • • •
Dupixent® (dupilumab), for patients >12 years of age with severe asthma or OCS-dependent asthma.10 Cinqair® (reslizumab), for use in patients >18 years of age.11 Fasenra® (benralizumab), for use in patients >12 years of age.7 Nucala (mepolizumab), for use in patients >12 years of age with an eosinophilic phenotype.12 Xolair® (omalizumab), for use in patients >6 years of age with a positive skin test or in vitro reactivity to a perennial aeroallergen.8
Not all biologics have the same mechanism of action or are approved for the same types of asthma-related symptoms. There is most likely overlap within the class, allowing for a first-line therapy to be defined within a formulary (possibly by step therapy), prior authorization, and tiering of benefits. Case management for this class of medications can be helpful to patients when adding another type of medication to what seems like an already complicated treatment plan. There may be an opportunity for dose optimization within the biological class, specifically with omalizumab, based on the dose range of 75 to 375 mg every two to four weeks. Evaluation of indication and response to current therapy would need to be considered and could be implemented as part of a prior authorization process. Dose optimization carries the potential for cost savings and better patient outcomes if it reduces the potential for side effects. Asthma affects patients in many different ways. The key to avoiding potential complications is to approach each patient individually and help them identify the best treatment course to manage their symptoms, preserve activities of daily living, and improve quality of life. It is imperative that patients understand proper techniques for administering their medications and how to identify their triggers in order to avoid them. A strong patient-provider relationship will help in the overall management of asthma symptoms and help to ensure patient compliance and adherence with their treatment plan.
“Most Recent National Asthma Data.” Centers for Disease Control and Prevention, May 2019, https://www.cdc.gov/asthma/most_ recent_national_asthma_data.htm.
“Asthma Surveillance Data.” Centers for Disease Control and Prevention, April 15, 2019, https://www.cdc.gov/asthma/nationalsurveillance-data/default.htm.
Nurmagambetov, T. et al. “The Economic Burden of Asthma in the United States, 2008-2013.” Annual American Thoracic Society, March 2018, https://www.ncbi.nlm.nih.gov/pubmed/29323930.
“Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma.” National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program, U.S. Department of Health and Human Services, National Institutes of Health, Aug. 28, 2007, https://www.ncbi.nlm.nih.gov/books/ NBK7232/.
“Global Strategy for Asthma Management and Prevention.” Global Initiative for Asthma, 2019, https://ginasthma.org/wp-content/ uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf.
Red Book® System. https://www.micromedexsolutions.com/.
Highlights of Prescribing Information for FASENRA. U.S. Food and Drug Administration, https://www.accessdata.fda.gov/drugsatfda_ docs/label/2017/761070s000lbl.pdf.
Highlights of Prescribing Information for XOLAIR. U.S. Food and Drug Administration, 2003, https://www.accessdata.fda.gov/ drugsatfda_docs/label/2016/103976s5225lbl.pdf.
IPD Analytics.® https://secure.ipdanalytics.com/User/Pharma/ Home/Insights.
10. Highlights of Prescribing Information for DUPIXENT. U.S. Food and Drug Administration, 2017, https://www.accessdata.fda.gov/ drugsatfda_docs/label/2017/761055lbl.pdf. 11. Highlights of Prescribing Information for CINQAIR. U.S. Food and Drug Administration, 2016, https://www.accessdata.fda.gov/ drugsatfda_docs/label/2016/761033lbl.pdf. 12. Highlights of Prescribing Information for NUCALA. U.S. Food and Drug Administration, 2015, https://www.accessdata.fda.gov/ drugsatfda_docs/label/2015/125526Orig1s000Lbl.pdf.
How are we helping? Through our specialty pharmacy program MRx Cares, our team is available to help members with asthma. Answer Questions
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Go to www.biosimilarslearn.com to learn more about biosimilars.
A Route to Adopting Biosimilars Based on the experience at a major health care institution. The adoption process and roles may vary by institution.
Deciding to adopt a biosimilar
Electing to adopt a biosimilar should begin by building knowledge about the product, followed by gaining a general agreement among stakeholders in the organization.
Building knowledge Physicians
Pharmacy Director or Change Leader
Department Finance Pharmacy and Director Therapeutics Committee Chairs
Assessing the payer landscape
Coverage & Reimbursement
Pharmacy Director or Change Leader
• Evaluating the clinical and financial implications of pursuing a biosimilar switch, including obtaining input from physicians, the supply chain, and other stakeholders • Investigating the clinical evidence - Examining the available information/data - Reviewing the Prescribing Information • Assessing the possibility of long-term savings to the organization, specifically for pharmacy directors, procurement and supply chain specialists, and finance directors • Getting an initial understanding of the payer landscape
Health Care Professionals
Building a consensus Pharmacy and Department Therapeutics Committee Chairs
• Presenting recommendations to the pharmacy and therapeutics committee for their buy-in • Obtaining endorsements from department chairs
Once the organization has decided to pursue the adoption of a biosimilar, certain steps should be followed to begin the transition to implementation. Communicating with stakeholders and educating patients about switching to a biosimilar can be instrumental to overall success.
Implementing a biosimilar Updating systems Pharmacy Director or Change Leader
Department Pharmacy and Chairs Therapeutics Committee
Addressing payer landscape and reimbursement Coverage & Reimbursement
Pharmacy Director or Change Leader
Health Care Professionals
Educating and communicating key information Patients
Health Care Professionals
Going live Coverage & Reimbursement
Health Care Pharmacists Professionals
Monitoring biosimilar use and experience Measuring and proving success Pharmacy Director or Change Leader
Pharmacy and Department Therapeutics Committee Chairs
• Optimizing the electronic health record (EHR) system • Streamlining order sets and protocols • Identifying appropriate patients • Reviewing billing requirements • Assessing the payer formulary • Evaluating payer utilization management criteria • Researching patient support programs
Additional considerations Inventory control - Stocking of new product - Handling of mixed inventory • Prescribing - Approved Indications • Dosing and frequency • Route of administration • Reimbursement team and payer communications • Possible reassignment of staff to identify patients and convert existing orders - What can be done for naïve patients? - Who will convert orders for non-naïve patients? • Proactive patient communication •
• Determining the implementation date • Outlining possible changes to the EHR system • Addressing insurance information • Communicating to patients that they are being switched to a biosimilar that has shown no clinically meaningful differences in terms of safety, purity, and potency
• Supporting patients through patient access programs • Providing physicians, nurses, pharmacists, and patients with a resource that includes consistent contact information for questions
Once a biosimilar has been implemented, a system should be established to measure the quality of the health care professional and patient experience, the utilization of the biosimilar, and the impact of biosimilar adoption on the organization as a whole. • Regularly reporting (eg, quarterly) to department chairs, the hospital administration, and the organization’s pharmacy and therapeutics committee
Possible reporting data Access and reimbursement issues • Drug use evaluations - Adverse drug reactions - Efficacy and patient outcomes
Overall patient experience Conversion rate • Inventory control • Stocking of new product • Handling of mixed inventory • •
As the health care landscape continues to change, consider whether adopting biosimilars presents an opportunity for your organization. Merck does not guarantee that your use of this information will help you achieve your biosimilars goals. This educational resource was prepared in consultation with and with the permission of a health care administrator at a major health care institution who had successfully implemented a biosimilars switch within their organization. Copyright © 2020 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All rights reserved. US-SBT-00870 05/20
Oncology Biosimilars: Update and Payer Considerations As biosimilars enter the market across specialty categories, payers must assess the potential impacts and prepare to promote adoption. While the relationship between generic drugs and their brand-name equivalents has been well-established, the relationship between biologic drugs and their biosimilars is not as clear.
Michael Ochowski, R.Ph. Pharmacy Informatics and EMR Support Group Health Cooperative of South Central Wisconsin
When a biologic drug patent expires, the U.S. Food and Drug Administration (FDA) approves biosimilars through a different process than it does traditional generic drugs.1 The abbreviated 351(k) biosimilar pathway requires manufacturers to demonstrate that there are no clinically meaningful differences in safety or efficacy between the biosimilars and their reference products. Traditional generic drugs are capable of achieving exact chemical likeness to the brand-name versions, but this is not the case with biosimilars due to complexities in their biosynthesis. Variability exists batch to batch in both reference and biosimilar products. Because of this, the FDA reviews a variety of data and evidence including, but not limited to, structural and functional characterization of the molecule, immunogenicity, pharmacokinetics, and at least one comparative clinical trial that establishes biosimilarity. While biosimilars have been used in Europe for more than 10 years, they have not gained traction as quickly in the U.S. Biosimilars were approved and came to market for autoimmune conditions, but nine years passed between the creation of the FDA 351(k) biosimilar approval pathway and the launch of the U.S.’s first therapeutic oncology biosimilar agent. In the same time frame, spending on oncology drugs in general has continued to rise across all lines of business. In 2019, oncology drugs were the primary drivers of cost for commercial payers.2
Available Biosimilars The first oncology biosimilars took the form of supportive care.3 Biosimilars for Neupogen®, Neulasta®, Epogen®, and Procrit® were approved and came to market in early 2018,4 giving the oncology community an opportunity to adjust to the idea of using biosimilars prior to the arrival of therapeutic oncology biosimilars.
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Table 1. Available Oncology Biosimilars and Relative Cost8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Cost (Based on Q1 2020 Wholesale Acquisition Cost) bevacizumab Avastin® (Genentech)
$796.94 (4 mL vial)
Mvasi™ (bevacizumab-awwb; Amgen)
$677.40 (4 mL vial)
Zirabev (bevacizumab-bvzr; Pfizer)
$613.40 (4 mL vial)
trastuzumab Herceptin® (Genentech)
$1,558.42 (150 mg vial)
Herzuma® (trastuzumab-pkrb; Teva)
$3,927.00 (420 mg vial)
Kanjinti™ (trastuzumab-anns; Amgen)
$3,697.26 (420 mg vial)
Ogivri (trastuzumab-dkst; Mylan)
$3,697.26 (420 mg vial)
Trazimera™ (trastuzumabqyyp; Pfizer)
$3,391.08 (420 mg vial only)
rituximab Rituxan® (Genentech) Truxima (rituximab-abbs; Teva) Ruxience® (rituximab-pvvr; Pfizer) ®
$939.52 (10 mL vial) $845.55 (10 mL vial) $716.80 (10 mL vial)
In July 2019, biosimilars bevacizumab-awwb (Mvasi™) and trastuzumab-anns (Kanjinti™) launched, quickly followed by rituximab-abbs (Truxima®) in November.5, 6, 7 Currently, there are multiple biosimilars commercially available for each of three reference products: bevacizumab (Avastin®), trastuzumab (Herceptin®), and rituximab (Rituxan®).
Differences from Generics Like traditional generic drugs, biosimilars are believed to present cost-savings opportunities for patients, providers, and payers. However, whereas it is common practice to substitute generics during dispensing, biosimilars are currently not considered interchangeable for their reference products in the U.S. — which is unique in holding this view. Based on the lack of incentives in the U.S., it seems unlikely that many manufacturers will perform the extra clinical trials necessary to achieve the FDA interchangeability designation.
Additionally, whereas generic drugs typically carry the same indications as the brand-name product, biosimilars are often subject to so-called “skinny labels,” which imply that the biosimilar may only be approved for some but not all of its reference product’s indications. For example, due to patent protection, biosimilars for bevacizumab currently do not carry Avastin®’s indication for ovarian cancer.
Payer Considerations Now that biosimilars are available, payers face the question of how they should manage, or even encourage, uptake in their use. The most apparent benefits relate to reductions in costs of care. From 2011 to 2016, average annual expenditures in the U.S. for Avastin®, Herceptin®, and Rituxan® totaled $8.6 billion.18 By 2018, as the first biosimilars were approaching launch, these three drugs were among the top five highest-spend oncology drugs for nine consecutive years.19 Given the continued increase in specialty drug approvals and the emergence of costly gene therapies in a number of categories, more-affordable biosimilars seem to be arriving at an opportune moment. Savings from biosimilars may not be realized immediately, specifically for the Medicare population. Due to the circumstances and verbiage related to biosimilars within the Centers for Medicare and Medicaid Services (CMS) 340B drug pricing program, biosimilars are not reimbursed based on average sales price plus 6% (ASP+6) markup — as is the norm for name-brand and generic drugs — but rather based on the same ASP+6 as their reference products. CMS has attempted to safeguard against these discrepancies via pass-through status, which would allow for some drugs and biologics to be reimbursed at ASP minus 22.5% rather than ASP+6, but different biosimilars for the same reference products could have different statuses. Because of this lack of standardization
Now that biosimilars are available, payers face the question of how they should manage, or even encourage, uptake in their use. Visit us online at www.magellanrx.com | 25
ONCOLOGY BIOSIMILAR UPDATE | Continued
among biosimilars, and because this price determines Medicare patients’ copays (provided the copay is based on a percentage of the drug price), the choice of biosimilar may mean that Medicare patients end up with a higher copay compared to commercially insured patients. Beyond cost savings, decisions on how to manage emerging biosimilars in the oncology space should consider payers, providers, and patients alike. In order to truly encourage the use of biosimilars and influence prescribing habits, payers will need to address concerns, uncertainty, and hesitancy from some providers. Surveys into U.S.-based oncologists’ perceptions of biosimilars have identified educational gaps around perceived barriers to provider acceptance, interchangeability, and whether biosimilars will retain all their reference products’ indications.21 Payers can address these areas of concern through upfront communication and information sharing — including cost-savings projections for all stakeholders based on historical utilization, consensus opinions from renowned thought leaders, and provider education related to both the category in general and specific factors impacting their market. Consensus among providers suggests that if managed care organizations are clear and proactive in communicating both product
26 | Magellan Rx Report | Summer 2020
information and anticipated goals and benefits of potential management strategies, then other concerns will likely be addressed in time as more and more providers become familiar with these new biosimilars. Payers can leverage several management strategies to drive patients and providers toward biosimilars. Managed care organizations may have an opportunity to encourage use of biosimilars currently on the market through policy-shaping efforts, such as placing step-therapy requirements when a biosimilar is approved for the same indication as the reference biologic. Magellan Rx created an oncology biosimilar action team during the latter part of 2018 to evaluate such a strategy on behalf of payer clients.23 After researching and examining various clinical and business aspects related to biosimilars, Magellan Rx identified key areas of focus to equip clients with a proactive management strategy. From there, health plan clients could either choose to implement step therapy for all patients who had not previously received the reference product (“new starts”) or manage oncology biosimilars at parity with the reference products. From the time clients began implementing step therapy — Sept. 1, 2019 — through the end of
January 2020, the percentage of requests for oncology biosimilars was 49% among clients who chose step therapy and 15.3% of requests for clients who chose a parity strategy. Limiting step-therapy requirements to treatment-naïve members can ease concerns around interchangeability and drive utilization toward less expensive treatments, all while shielding patients and providers from forced switches during ongoing treatment.
Long-term follow-up will be needed to fully assess biosimilars’ clinical and financial impacts on the market. In the interim, expect to see additional biosimilars entering the market. Managed care organizations can prepare by putting strategies in place to proactively manage the balance of biosimilars and reference products. Payers equipped with proactive utilization-management strategies for oncology biosimilars can capitalize on early utilization shifts, thereby helping to minimize disruption and allowing for easier adoption of less-expensive biosimilar products.
Lyman, Gary H. et al. “Rationale, Opportunities, and Reality of Biosimilar Medications.” New England Journal of Medicine, May 24, 2018, https://pubmed.ncbi.nlm.nih.gov/29791832.
Magellan Rx Medical Pharmacy Trend Report 2019, Magellan Rx Management, https://www1.magellanrx.com/documents/2020/03/ mrx-medical-pharmacy-trend-report-2019.pdf.
Cornes, Paul and Matti Aapro. “The Impact of Biosimilars in Supportive Care in Cancer.” European Oncology & Haematology, Feb. 22, 2018, https://doi.org/10.17925/EOH.2018.14.1.20.
Retacrit® [package insert]. Lake Forest, IL: Hospira; May 2018.
Mvasi™. [package insert]. Thousand Oaks, CA; Amgen; September 2017.
Kanjinti™. [package insert]. Thousand Oaks, CA; Amgen; June 2019.
Truxima . [package insert]. Yeonsu-gu, Incheon, Korea; Celltrion; November 2018.
Avastin®. [package insert]. South San Francisco, CA; Genentech; May 2020.
Zirabev®. [package insert]. New York, NY; Pfizer; June 2019.
10. Herceptin®. [package insert]. South San Francisco, CA; Genentech; September 2019. 11. Herzuma®. [package insert]. North Wales, PA; Teva Pharmaceuticals; December 2018. 12. “FDA approves Herzuma as a biosimilar to Herceptin.” U.S. Food and Drug Administration, Dec. 18, 2018, https://www.fda.gov/Drugs/ InformationOnDrugs/ApprovedDrugs/ucm628724.htm. 13. Ogivri. [package insert]. Zurich, Switzerland; Mylan; December 2019. 14. Trazimera™. [package insert]. New York, NY; Pfizer; March 2019.
15. Davio, Kelly. “FDA Approves Celltrion’s Rituximab Biosimilar, Truxima.” The Center for Biosimilars. American Journal of Managed Care, Nov. 28, 2018, https://www.centerforbiosimilars.com/news/fda-approvescelltrions-rituximab-biosimilar-truxima. 16. Rituxan®. [package insert]. South San Francisco, CA; Genentech; October 2018. 17. Ruxience®. [package insert]. New York, NY; Pfizer; July 2019. 18. IBM Micromedex RED BOOK. IBM, https://www.ibm.com/products/ micromedex-red-book. 19. Hong, S.J. et al. “Spending on Antineoplastic Agents in the United States, 2011 to 2016.” Journal of Oncology Practice, Sept. 18, 2018, https://www.ncbi.nlm.nih.gov/pubmed/30226791. 20. Magellan Rx Medical Pharmacy Trend Report 2018, Magellan Rx Management, https://www1.magellanrx.com/documents/2019/03/ medical-pharmacy-trend-report_2018.pdf. 21. “The Mysteries of Pass-Through Status: Why Medicare and Seniors Are Now Paying More for Lower-Cost Biosimilars at Hospitals.” https://www.drugchannels.net/2018/04/the-mysteries-of-passthrough-status.html. 22. Nabhan, Chadi et al. “Community Oncologists’ Perception and Acceptance of Biosimilars in Oncology.” Journal of Clinical Pathways, March 2018, https://www.journalofclinicalpathways.com/article/ community-oncologists-perception-and-acceptance-biosimilarsoncology. 23. Borgert, Rebecca et al. “The Long-awaited Launch of Oncology Biosimilars: Evaluating the Impact of Payer and Provider Strategies on Early Adoption.” AMCP 2020. Magellan Rx Management, April 2020, https://www1.magellanrx.com/documents/2020/04/the-longawaited-launch-of-oncology-biosimilars-evaluating-the-impact-ofpayer-and-provider-strategies-on-early-adoption.pdf/.
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FASENRA is indicated as an add-on maintenance treatment of patients 12 years and older with severe eosinophilic asthma.
POWER TO PREVENT
The primary endpoint for SIROCCO (Trial 1) and CALIMA (Trial 2) was the rate of asthma exacerbations in patients with baseline blood eosinophil counts of ≥300 cells/μL who were taking high-dose ICS and LABA1 • In SIROCCO: 51% reduction in AER* (0.74; n=267) in patients who received FASENRA + SOC compared to placebo + SOC (1.52; n=267) (48 weeks, P<0.0001)1,2 • In CALIMA: 28% reduction in AER (0.73; n=239) in patients who received FASENRA + SOC compared to placebo + SOC (1.01; n=248) (56 weeks, P=0.019)1,3
ASTHMA EXACERBATION PREVENTION DATA
OVER 2 YEARS4,5
In patients who continued on FASENRA Q8W from SIROCCO and CALIMA into BORA EXACERBATION DATA FROM BASELINE IN YEARS 1 AND 2†‡5 Asthma exacerbation rate (AER) data in Year 1 maintained in Year 2†‡5
Baseline 2.7 §
Pre-Study Baseline AER*
SIROCCO and CALIMA (pooled)
BORA (Phase 3 Safety Extension Trial)
IN AER* FROM BASELINE
IN AER* FROM BASELINE
Year 1 AER: 0.65
Year 2 AER: 0.48
FASENRA + SOC (n=318)
FASENRA + SOC (n=318)
The analyses of these endpoints were not multiplicity protected. Results are descriptive only.
IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS Known hypersensitivity to benralizumab or excipients. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA. These
reactions generally occur within hours of administration, but in some instances have a delayed onset (ie, days). Discontinue in the event of a hypersensitivity reaction. Acute Asthma Symptoms or Deteriorating Disease FASENRA should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.
FASENRA is not indicated for treatment of other eosinophilic conditions or for the relief of acute bronchospasm or status asthmaticus.
EXACERBATION PREVENTION DATA: BORA
OF PATIENTS WHO CONTINUED ON Q8W DOSING FROM SIROCCO OR CALIMA INTO BORA (56 WEEKS) HAD
The analyses of these endpoints were not multiplicity protected. Results are descriptive only. In SIROCCO and CALIMA, FASENRA and placebo were administered plus standard of care (SOC), which is defined as high-dose ICS/LABA (inhaled corticosteroids/long-acting ß2-agonist) with or without other controllers, including systemic steroids. In SIROCCO and CALIMA, the primary endpoint was the rate of asthma exacerbations in patients with baseline blood eosinophil counts ≥300 cells/μL who were taking high-dose ICS and LABA.1 In BORA, patients from SIROCCO and CALIMA were to be maintained on their same dose of ICS/LABA.4 The most common adverse reactions (incidence greater than or equal to 3%) associated with the use of FASENRA (and placebo) included headache 8% (6%); pharyngitis 5% (3%); pyrexia 3% (2%); and hypersensitivity reactions 3% (3%).1 *Annual exacerbation rate (AER) was defined as the total number of exacerbations multiplied by 365.25, divided by the total duration of follow-up (days) within the treatment group. ‡ Patients who had baseline blood eosinophil counts ≥300 cells/μL, receiving high-dose ICS/LABA, and who received FASENRA 30 mg Q8W during SIROCCO, CALIMA, and BORA.5 § Exacerbation rate over the year before pivotal study entry.5 II In patients with baseline blood eosinophil counts ≥300 cells/μL in SIROCCO and CALIMA who continued on FASENRA every 8 weeks (n=339).4
M A K E FA S E N R A YO U R F I R S T C H O I C E R E S P I R ATO RY B I O LO G I C IMPORTANT SAFETY INFORMATION (cont’d) WARNINGS AND PRECAUTIONS (cont’d) Reduction of Corticosteroid Dosage Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. Reductions in corticosteroid dose, if appropriate,
Please see additional Important Safety Information on next page and Brief Summary of Prescribing Information on adjacent pages.
FASENRA is indicated as an add-on maintenance treatment of patients 12 years and older with severe eosinophilic asthma. FASENRA is not indicated for treatment of other eosinophilic conditions or for the relief of acute bronchospasm or status asthmaticus.
STUDY DESIGNS SIROCCO and CALIMA (Trials 1 and 2) SIROCCO (48-week) and CALIMA (56-week) were 2 randomized, double-blind, parallel-group, placebo-controlled, multicenter studies comparing FASENRA 30 mg SC Q4W for the first 3 doses, then Q8W thereafter; benralizumab 30 mg SC Q4W, and placebo SC. A total of 1204 (SIROCCO) and 1306 (CALIMA) patients aged 12-75 years old with severe asthma uncontrolled on high-dose ICS (SIROCCO) and medium- to high-dose ICS (CALIMA) plus LABA with or without additional controllers were included. Patients had a history of ≥2 exacerbations requiring systemic corticosteroids or temporary increase in usual dosing in the previous year. Patients were stratified by geography, age, and blood eosinophil counts (≥300 cells/μL and <300 cells/μL). The primary endpoint was annual exacerbation rate ratio vs placebo in patients with blood eosinophil counts of ≥300 cells/μL on high-dose ICS and LABA. Exacerbations were defined as a worsening of asthma that led to use of systemic corticosteroids for ≥3 days, temporary increase in a stable OCS background dose for ≥3 days, emergency/urgent care visit because of asthma that needed systemic corticosteroids, or inpatient hospital stay of ≥24 hours because of asthma. Key secondary endpoints were pre-bronchodilator FEV1 and total asthma symptom score at Week 48 (SIROCCO) and Week 56 (CALIMA) in the same population.2,3
BORA (Phase 3 Safety Extension Trial) A randomized, double-blind, parallel-group, phase 3 extension study that enrolled patients who completed SIROCCO or CALIMA (n=1576). Patients enrolled in the previous studies were aged 12-75 years and had physician-diagnosed asthma requiring treatment with medium-dosage or high-dosage ICS plus LABA for at least 12 months with or without additional controllers prior to enrollment. Patients originally randomized to FASENRA continued FASENRA 30 mg SC Q8W or benralizumab SC Q4W. Patients previously receiving placebo were re-randomized 1:1 to FASENRA 30 mg SC Q4W for the first 3 doses, then Q8W thereafter or benralizumab 30 mg SC Q4W except for adolescent patients in the EU who were randomized to FASENRA 30 mg SC Q8W. Patients were to be maintained on their same dose of ICS/LABA. End of treatment was at Week 56 for adults and Week 108 for adolescents. The primary objective was assessment of safety and tolerability. Secondary objectives included assessments of asthma exacerbations, pre-bronchodilator forced expiratory volume in 1 second (FEV1), and impact of treatment on blood eosinophil levels. Results are at Weeks 68 (adult follow-up) and 56 (adolescents), unless otherwise noted.4 References: 1. FASENRA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; October 2019. 2. Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebocontrolled phase 3 trial. Lancet. 2016;388:2115-2127. 3. FitzGerald JM, Bleecker ER, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388:2128-2141. 4. Busse WW, Bleecker ER, FitzGerald JM, et al. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir Med. 2019;7:46-59. 5. FitzGerald JM, Bleecker ER, Bourdin A, et al. Two-year integrated efficacy and safety analysis of benralizumab SIROCCO, CALIMA, ZONDA, and BORA trials in severe asthma. Presented at: the American Thoracic Society (ATS) International Conference; May 17-22, 2019; Dallas, TX.
IMPORTANT SAFETY INFORMATION (cont’d) WARNINGS AND PRECAUTIONS (cont’d) Reduction of Corticosteroid Dosage (cont’d) should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy. Parasitic (Helminth) Infection It is unknown if FASENRA will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with FASENRA. If patients become infected while receiving FASENRA and do not respond to antihelminth treatment, discontinue FASENRA until infection resolves. ADVERSE REACTIONS The most common adverse reactions (incidence ≥ 5%) include headache and pharyngitis. Injection site reactions (eg, pain, erythema, pruritus, papule) occurred at a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treated with placebo.
USE IN SPECIFIC POPULATIONS A pregnancy exposure registry monitors pregnancy outcomes in women exposed to FASENRA during pregnancy. To enroll call 1-877-311-8972 or visit www.mothertobaby.org/fasenra. The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. INDICATION FASENRA is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. • FASENRA is not indicated for treatment of other eosinophilic conditions • FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus
Please see Brief Summary of Prescribing Information on adjacent pages. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088. FASENRA is a registered trademark of the AstraZeneca group of companies. ©2020 AstraZeneca. All rights reserved. US-40027 4/20
FASENRA® (benralizumab) injection, for subcutaneous use Initial U.S. Approval: 2017 Brief Summary of Prescribing Information. For complete prescribing information consult official package insert. INDICATIONS AND USAGE FASENRA is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype [see Clinical Studies (14) in the full Prescribing Information]. Limitations of use: • FASENRA is not indicated for treatment of other eosinophilic conditions. • FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus. DOSAGE AND ADMINISTRATION Recommended Dose FASENRA is for subcutaneous use only. The recommended dose of FASENRA is 30 mg administered once every 4 weeks for the first 3 doses, and then once every 8 weeks thereafter by subcutaneous injection into the upper arm, thigh, or abdomen. General Administration Instructions FASENRA is intended for use under the guidance of a healthcare provider. In line with clinical practice, monitoring of patients after administration of biologic agents is recommended [see Warnings and Precautions (5.1) in the full Prescribing Information]. Administer FASENRA into the thigh or abdomen. The upper arm can also be used if a healthcare provider or caregiver administers the injection. Prior to administration, warm FASENRA by leaving carton at room temperature for about 30 minutes. Visually inspect FASENRA for particulate matter and discoloration prior to administration. FASENRA is clear to opalescent, colorless to slightly yellow, and may contain a few translucent or white to off-white particles. Do not use FASENRA if the liquid is cloudy, discolored, or if it contains large particles or foreign particulate matter. Prefilled Syringe The prefilled syringe is for administration by a healthcare provider. Autoinjector (FASENRA PEN™) FASENRA PEN is intended for administration by patients/caregivers. Patients/caregivers may inject after proper training in subcutaneous injection technique, and after the healthcare provider determines it is appropriate. Instructions for Administration of FASENRA Prefilled Syringe (Healthcare Providers) Refer to Figure 1 to identify the prefilled syringe components for use in the administration steps. Syringe Label with Needle guard Figure 1 activation clips
Do not touch the needle guard activation clips to prevent premature activation of the needle safety guard. 1 Grasp the syringe body, not the plunger, to remove prefilled syringe from the tray. Check the expiration date on the syringe. The syringe may contain small air bubbles; this is normal. Do not expel the air bubbles prior to administration. NEEDLE GUARD WINGS 2 Do not remove needle cover until ready to inject. Hold the syringe body and remove the needle cover by pulling straight off. Do not hold the plunger or plunger head while removing the needle cover or the plunger may move. If the prefilled syringe is damaged or contaminated (for example, dropped without needle cover in place), discard and use a new prefilled syringe.
Gently pinch the skin and insert the needle at the recommended injection site (i.e., upper arm, thigh, or abdomen).
Inject all of the medication by pushing in the plunger all the way until the plunger head is completely between the needle guard activation clips. This is necessary to activate the needle guard.
After injection, maintain pressure on the plunger head and remove the needle from the skin. Release pressure on the plunger head to allow the needle guard to cover the needle. Do not re-cap the prefilled syringe.
6 Discard the used syringe into a sharps container. Instructions for Administration of FASENRA PEN Refer to the FASENRA PEN ‘Instructions for Use’ for more detailed instructions on the preparation and administration of FASENRA PEN [See Instructions for Use in the full Prescribing Information]. A patient may self-inject or the patient caregiver may administer FASENRA PEN subcutaneously after the healthcare provider determines it is appropriate. CONTRAINDICATIONS FASENRA is contraindicated in patients who have known hypersensitivity to benralizumab or any of its excipients [see Warnings and Precautions (5.1) in the full Prescribing Information]. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred following administration of FASENRA. These reactions generally occur within hours of administration, but in some instances have a delayed onset (i.e., days). In the event of a hypersensitivity reaction, FASENRA should be discontinued [see Contraindications (4) in the full Prescribing Information]. Acute Asthma Symptoms or Deteriorating Disease FASENRA should not be used to treat acute asthma symptoms or acute exacerbations. Do not use FASENRA to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with FASENRA. Reduction of Corticosteroid Dosage Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy. Parasitic (Helminth) Infection Eosinophils may be involved in the immunological response to some helminth infections. Patients with known helminth infections were excluded from participation in clinical trials. It is unknown if FASENRA will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with FASENRA. If patients become infected while receiving treatment with FASENRA and do not respond to anti-helminth treatment, discontinue treatment with FASENRA until infection resolves. ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: • Hypersensitivity Reactions [see Warnings and Precautions (5.1) in the full Prescribing Information] Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Across Trials 1, 2, and 3, 1,808 patients received at least 1 dose of FASENRA [see Clinical Studies (14) in the full Prescribing Information]. The data described below reflect exposure to FASENRA in 1,663 patients, including 1,556 exposed for at least 24 weeks and 1,387 exposed for at least 48 weeks. The safety exposure for FASENRA is derived from two Phase 3 placebo-controlled studies (Trials 1 and 2) from 48 weeks duration [FASENRA every 4 weeks (n=841), FASENRA every 4 weeks for 3 doses, then every 8 weeks (n=822), and placebo (n=847)]. While a dosing regimen of FASENRA every 4 weeks was included in clinical trials, FASENRA administered every 4 weeks for 3 doses, then every 8 weeks thereafter is the recommended dose [see Dosage and Administration (2.1) in the full Prescribing Information]. The population studied was 12 to 75 years of age, of which 64% were female and 79% were white. Adverse reactions that occurred at greater than or equal to 3% incidence are shown in Table 1. Table 1. Adverse Reactions with FASENRA with Greater than or Equal to 3% Incidence in Patients with Asthma (Trials 1 and 2) Adverse Reactions FASENRA Placebo (N=822) (N=847) % % Headache 8 6 Pyrexia 3 2 Pharyngitis* 5 3 3 3 Hypersensitivity reactions† * Pharyngitis was defined by the following terms: ‘Pharyngitis’, ‘Pharyngitis bacterial’, ‘Viral pharyngitis’, ‘Pharyngitis streptococcal’. † Hypersensitivity Reactions were defined by the following terms: ‘Urticaria’, ‘Urticaria papular’, and ‘Rash’ [see Warnings and Precautions (5.1) in the full Prescribing Information].
FASENRA® (benralizumab) injection, for subcutaneous use 28-Week Trial Adverse reactions from Trial 3 with 28 weeks of treatment with FASENRA (n=73) or placebo (n=75) in which the incidence was more common in FASENRA than placebo include headache (8.2% compared to 5.3%, respectively) and pyrexia (2.7% compared to 1.3%, respectively) [see Clinical Studies (14) in the full Prescribing Information]. The frequencies for the remaining adverse reactions with FASENRA were similar to placebo. Injection site reactions In Trials 1 and 2, injection site reactions (e.g., pain, erythema, pruritus, papule) occurred at a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treated with placebo. Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to benralizumab in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. Overall, treatment-emergent anti-drug antibody response developed in 13% of patients treated with FASENRA at the recommended dosing regimen during the 48 to 56 week treatment period. A total of 12% of patients treated with FASENRA developed neutralizing antibodies. Anti-benralizumab antibodies were associated with increased clearance of benralizumab and increased blood eosinophil levels in patients with high anti-drug antibody titers compared to antibody negative patients. No evidence of an association of anti-drug antibodies with efficacy or safety was observed. The data reflect the percentage of patients whose test results were positive for antibodies to benralizumab in specific assays. Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during post approval use of FASENRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to FASENRA or a combination of these factors. Immune System Disorders: Hypersensitivity reactions, including anaphylaxis. DRUG INTERACTIONS No formal drug interaction studies have been conducted. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to FASENRA during pregnancy. Healthcare providers can enroll patients or encourage patients to enroll themselves by calling 1-877-311-8972 or visiting mothertobaby.org/Fasenra. Risk Summary The data on pregnancy exposure from the clinical trials are insufficient to inform on drugassociated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. In a prenatal and postnatal development study conducted in cynomolgus monkeys, there was no evidence of fetal harm with IV administration of benralizumab throughout pregnancy at doses that produced exposures up to approximately 310 times the exposure at the maximum recommended human dose (MRHD) of 30 mg SC [see Data]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk: In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control. Data Animal Data In a prenatal and postnatal development study, pregnant cynomolgus monkeys received benralizumab from beginning on GD20 to GD22 (dependent on pregnancy determination), on GD35, once every 14 days thereafter throughout the gestation period and 1-month postpartum (maximum 14 doses) at doses that produced exposures up to approximately 310 times that achieved with the MRHD (on an AUC basis with maternal IV doses up to 30 mg/kg once every 2 weeks). Benralizumab did not elicit adverse effects on fetal or neonatal growth (including immune function) up to 6.5 months after birth. There was no evidence of treatment-related external, visceral, or skeletal malformations. Benralizumab was not teratogenic in cynomolgus monkeys. Benralizumab crossed the placenta in cynomolgus monkeys. Benralizumab concentrations were approximately equal in mothers and infants on postpartum day 7, but were lower in infants at later time points. Eosinophil counts were suppressed in infant monkeys with gradual recovery by 6 months postpartum; however, recovery of eosinophil counts was not observed for one infant monkey during this period.
Lactation Risk Summary There is no information regarding the presence of benralizumab in human or animal milk, and the effects of benralizumab on the breast fed infant and on milk production are not known. However, benralizumab is a humanized monoclonal antibody (IgG1/κ-class), and immunoglobulin G (IgG) is present in human milk in small amounts. If benralizumab is transferred into human milk, the effects of local exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to benralizumab are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for benralizumab and any potential adverse effects on the breast-fed child from benralizumab or from the underlying maternal condition. Pediatric Use There were 108 adolescents aged 12 to 17 with asthma enrolled in the Phase 3 exacerbation trials (Trial 1: n=53, Trial 2: n=55). Of these, 46 received placebo, 40 received FASENRA every 4 weeks for 3 doses, followed by every 8 weeks thereafter, and 22 received FASENRA every 4 weeks. Patients were required to have a history of 2 or more asthma exacerbations requiring oral or systemic corticosteroid treatment in the past 12 months and reduced lung function at baseline (pre-bronchodilator FEV1<90%) despite regular treatment with medium or high dose ICS and LABA with or without OCS or other controller therapy. The pharmacokinetics of benralizumab in adolescents 12 to 17 years of age were consistent with adults based on population pharmacokinetic analysis and the reduction in blood eosinophil counts was similar to that observed in adults following the same FASENRA treatment. The adverse event profile in adolescents was generally similar to the overall population in the Phase 3 studies [see Adverse Reactions (6.1) in the full Prescribing Information]. The safety and efficacy in patients younger than 12 years of age has not been established. Geriatric Use Of the total number of patients in clinical trials of benralizumab, 13% (n=320) were 65 and over, while 0.4% (n=9) were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. OVERDOSAGE Doses up to 200 mg were administered subcutaneously in clinical trials to patients with eosinophilic disease without evidence of dose-related toxicities. There is no specific treatment for an overdose with benralizumab. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary. PATIENT COUNSELING INFORMATION Advise the patients and/or caregivers to read the FDA-approved patient labeling (Patient Information and Instructions for Use for FASENRA PEN) before the patient starts using FASENRA and each time the prescription is renewed as there may be new information they need to know. Provide proper training to patients and/or caregivers on proper subcutaneous injection technique using the FASENRA PEN, including aseptic technique, and the preparation and administration of FASENRA PEN prior to use. Advise patients to follow sharps disposal recommendations [see Instructions for Use in the full Prescribing Information]. Hypersensitivity Reactions Inform patients that hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA. These reactions generally occurred within hours of FASENRA administration, but in some instances had a delayed onset (i.e., days). Instruct patients to contact their healthcare provider if they experience symptoms of an allergic reaction [see Warnings and Precautions (5.1) in the full Prescribing Information]. Not for Acute Symptoms or Deteriorating Disease Inform patients that FASENRA does not treat acute asthma symptoms or acute exacerbations. Inform patients to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with FASENRA [see Warnings and Precautions (5.2) in the full Prescribing Information]. Reduction of Corticosteroid Dosage Inform patients to not discontinue systemic or inhaled corticosteroids except under the direct supervision of a physician. Inform patients that reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy [see Warnings and Precautions (5.3) in the full Prescribing Information]. Pregnancy Exposure Registry Inform women there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to FASENRA during pregnancy and that they can enroll in the Pregnancy Exposure Registry by calling 1-877-311-8972 or by visiting mothertobaby.org/Fasenra [see Use in Specific Populations (8.1) in the full Prescribing Information]. Manufactured by AstraZeneca AB Södertälje, Sweden SE-15185 US License No. 2059 Distributed by AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 FASENRA is a trademark of the AstraZeneca group of companies. ©AstraZeneca 2019 Rev. 10/19 US-30659 10/19
Sickle Cell Disease: Clinical and Management Update Most SCD patients today are not being treated appropriately due to underutilization of current therapies, but emerging therapies present an opportunity to provide more-effective management of SCD. Sickle cell disease (SCD) causes red blood cells to cluster together, which leads to vascular occlusion and impairs oxygen supply to tissues, causing cell destruction and a shortage of healthy blood cells. These blockages can cause vaso-occlusive crises (VOCs), a painful condition that can lead to hospitalizations. Symptoms of SCD include infection, pain, anemia, swelling of the hands and feet, and fatigue. The condition can advance to organ damage.1 SCD primarily affects people from, or descended from, African, Mediterranean, and Spanish-speaking countries. An estimated 100,000 Americans have SCD, and the condition occurs in an estimated 1 in 365 African American births. Approximately 1 in 13 African American babies are born with sickle cell trait (SCT).1 Samir Mistry, Pharm.D. Vice President, Pharmacy PreferredOne
SCD affects millions around the world and has very high associated medical costs — over $1.1 billion annually in the U.S. For adults, the total cost per patient per month peaks at around $2,853. For patients who reach the age of 45, annual costs are estimated at $1 million.2 Medicaid paid for about 66% of hospital stays for SCD in 2004, and less than 70% of doctors in the U.S. accepted new Medicaid patients. A 2016 study showed that about 49.6% of hospital stays for patients with a SCD diagnosis were paid for by Medicaid, and, according to 2014-2015 data, only 71% of doctors in the U.S. accepted new Medicaid patients;3, 4 thus, this subset of patients has limited access to care, which affects health outcomes.1, 2
Course and Pathogenesis SCD is autosomal recessive and caused by a mutation in the ß-globin chain of the hemoglobin molecule (HBB) in infancy.5 People who inherit one sickle cell gene and one normal gene have SCT, and though they do not have SCD symptoms, they can pass on the trait.1 The mutation causes the sixth amino acid in the ß-globin chain to be switched from glutamic acid to valine.5 The mutated hemoglobin molecule is prone to sticking to other hemoglobin molecules under certain conditions.
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SICKLE CELL DISEASE | Continued
Hematologists, pediatric hematologists, ophthalmologists, and pulmonologists are typically tasked with SCD management. While normal red blood cells last 90 to 120 days and can freely flow through the body, HbS molecules become viscous and cannot travel as freely. VOCs can prevent oxygen from reaching tissues, causing tissues to become ischemic. VOCs usually occur in the lower back, legs, hips, abdomen, and chest and can last days or even weeks. If VOC-associated pain reaches the chest, it can cause an infection of the lungs — acute chest syndrome — a leading cause of death for SCD patients.5
Patients often present to the emergency department (ED) when they are undergoing a VOC.6 Opioids are often prescribed to manage the excruciating pain that accompanies VOCs; however, studies show that not all patients benefit from pain relievers, possibly due to opioid tolerance or inappropriately low doses of prescribed opioids — which is especially common from ED doctors who lack full understanding of the patient’s medical history. Curbing opioid use due to the potential for abuse or misuse is another challenge. Alternatives to opioids for SCD-associated pain management are being researched.5
Diagnosis Newborns in the U.S. receive a routine blood test that checks for defective forms of hemoglobin to detect SCD. Adults can also undergo this blood test to determine if they are a carrier for SCTs. Patients with SCD will be diagnosed with one of the three main types: HbSS, HbSC, or HbS. Symptoms usually do not present until around 5-6 months of age, as patients are initially protected by their fetal hemoglobin.6
There are three major types of SCD. » HbSS, or sickle cell anemia, is the most severe form and occurs when a person inherits two sickle cell genes from each parent. » HbSC occurs when a person inherits one sickle cell gene from one parent and one gene for abnormal hemoglobin C from the other. » HbS ß-thalassemia occurs when a person inherits one sickle cell gene from one parent and one gene for a type of anemia called ß-thalassemia.1
Complications Splenic sequestration, which usually occurs in younger children and can be severe and life-threatening, is a sudden phenomenon wherein large amounts of sickle cells get trapped in the spleen. The hemoglobin can drop rapidly, causing anemia quickly and leading to hypovolemic shock. Treatment is needed quickly, with focus on expanding blood volume through blood transfusions.6 Other SCD complications include infections, hand-foot syndrome, eye disease, acute chest syndrome, and stroke.
Treatment Challenges Hematologists, pediatric hematologists, ophthalmologists, and pulmonologists are typically tasked with SCD management.
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Current Treatment Options Infection Prevention and Treatment: Antibiotics and Vaccinations Immunization and prophylactic treatment with antibiotics can reduce the risk of infection and further complications. Children who have SCD at birth should take penicillin twice daily until 5 years of age to prevent pneumococcal sepsis. Infections are a major cause of death in patients with SCD; therefore, it is essential that they get certain vaccinations to prevent infections. Pediatric patients should receive Haemophilus influenzae type b (Hib), Meningococcal conjugate, and Pneumococcal conjugate (PCV13, or Prevnar 13).6
VOC Prevention and Treatment: Hydroxyurea and L-glutamine Hydroxyurea and L-glutamine are used to prevent or reduce the frequency of acute and chronic complications. Hydroxyurea stimulates the production of HbF, or fetal hemoglobin, and, when used long-term, can reduce the frequency of acute pain crises and the need for blood transfusions. It is only indicated for adults with three or more moderate-to-severe VOCs a year. It is proven to reduce the frequency of painful VOC episodes by 50%
and raise hemoglobin,7 and it is associated with increased survival rates in patients with SCD.8 However, it can also cause myelosuppression, or bone marrow suppression; therefore, hematology labs must be monitored regularly. When taking this hazardous agent, contraception is required for both males and females, and patients should avoid live vaccines.9 L-glutamine oral powder, or Endari®, is approved for adults and children older than 5 years with SCD who have failed hydroxyurea or for concurrent use. Glutamine can reduce acute complications related to SCD such as pain crises. Each 5g dose is mixed with 8 ounces of cold or room-temperature liquid or 6 ounces of food.10 Glutamine 1,500 mg is also available as an over-thecounter product, but this is generally not recommended since it has not been approved by the U.S. Food and Drug Administration (FDA).
Pain Management: Opioids and Other Pain Relievers VOCs usually require IV opioids or patient-controlled analgesia to tolerate the severe pain.6 Acute moderate pain is usually managed with a less potent opioid, such as codeine or hydrocodone, in combination with an NSAID, such as ibuprofen or acetaminophen. For acute severe pain, stronger opioids, such as intravenous morphine or fentanyl may be used.
Chelation Therapy SCD patients receive regular blood transfusions, and within each unit of packed red blood cells is about 250 mg of iron. After 20 of these transfusions, the body accumulates excess iron due to saturation of transferrin. Iron overload can cause organ damage. Chelation therapy is used to manage the iron load that patients receive from blood transfusions. Oral chelation therapy has recently become available: deferasirox (Exjade®, Jadenu®) and deferiprone (Ferriprox®).11
Transplantation Bone marrow or stem cell transplantation is currently the only real cure for SCD. Unfortunately, it is not utilized widely due to the high costs and risks that accompany such an invasive treatment. There is significant toxicity as well as serious side effects and even death associated with this procedure. Additionally, for these transplants to work effectively, the bone marrow must be a close match.1
New Pharmacotherapies The FDA recently approved two new drugs: crizanlizumab-tmca (Adakveo®) and voxelotor (Oxbryta™). Adakveo® is an intravenous infusion-administered monoclonal antibody developed by
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SICKLE CELL DISEASE | Continued
The FDA recently approved two new drugs: crizanlizumabtmca (Adakveo®) and voxelotor (Oxbryta™). Novartis. It is used to reduce the frequency of VOCs in adults 16 years and older with SCD.12 Oxbryta™ is an oral medication developed by Global Blood Therapeutics and approved for people with SCD aged 12 years and older and with a pretreatment hemoglobin level of 10.5 g/dL or less. It works by keeping red blood cells in an oxygenated state and preventing the hemoglobin from sticking together.13
Crizanlizumab The SUSTAIN study evaluated crizanlizumab in a randomized, double-blind, phase two, placebo-controlled clinical trial. The post-hoc analysis looked at patients with SCD and randomized them to different doses of crizanlizumab: 2.5 mg/kg, 5 mg/kg, or placebo, administered via IV 14 times over 52 weeks. Patients were randomized using a block design and then stratified according to the number of VOCs in the prior year (two to four or five to 10) and whether concomitantly using hydroxyurea. The primary endpoint analyzed was the yearly VOC with crizanlizumab versus with placebo. Secondary endpoints were further analyzed and showed that crizanlizumab significantly increased time to first VOC versus placebo.14 SUSTAIN Results: » 25.8% of patients receiving crizanlizumab did not experience a VOC, compared with 16.9% of those receiving placebo. This pattern was also shown in each subgroup, especially for patients who had experienced many VOCs in the year prior. » 28% of patients receiving 5 mg/kg crizanlizumab were VOC-free, compared to 4.2% of patients receiving placebo. » 33.3% of patients using hydroxyurea concomitantly were VOC-free, compared to 17.5% of patients who were not using hydroxyurea. » 31.9% of patients with the HbSS genotype were VOC-free, compared with 17% of patients without it. » Time to first VOC for patients receiving crizanlizumab was 4.07 months, compared with 1.12 months for patients receiving placebo.
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Overall, this study was successful, as it showed that patients had a decreased chance of a VOC occurring and a delay in the time to the first VOC while taking crizanlizumab.14
Voxelotor (Oxbryta™) Voxelotor (Oxbryta™) was studied in a phase three, multicenter, double-blind, randomized, placebo-controlled trial. Two doses of voxelotor were analyzed to compare safety and efficacy. 274 participants were randomized in a 1:1:1 ratio to receive once-daily voxelotor 1,500 mg, once-daily voxelotor 900 mg, or placebo. Most participants had SCD, and about two-thirds were already on hydroxyurea treatment. The primary endpoint was the percentage of patients with a hemoglobin response, shown as an increase of 1.0 g/dL from baseline at week 24. Results: » 51% of patients receiving voxelotor 1,500 mg and 33% of patients receiving 900 mg had a hemoglobin response, compared to 7% in the placebo group, which is a significant difference. » Voxelotor improved anemia between baseline and week 24 compared to placebo. » Most adverse effects reported by patients were not related to the drug or placebo. This study was considered a success, as voxelotor significantly increased hemoglobin levels and reduced hemolysis markers, although it did not show a statistical benefit in VOC reduction.15
ICER Review A March 2020 Institute for Clinical and Economic Review (ICER) Report issued key clinical findings on SCD therapies.16 » Crizanlizumab, the report concluded, will provide a positive net health benefit; however, considering the difficulties in estimating the amount of long-term organ system benefits and the uncertainty about long-term safety, ICER could only make the conclusion with moderate certainty and gave the therapy a B+ rating. » Voxelotor got a “promising but inconclusive” rating in the report, due to difficulties in ascertaining the clinical benefit of the drug with data available at its launch; however, ICER found that the clinical benefits are likely to be somewhat greater than those experienced with usual care.16 » L-Glutamine was rated as “promising but inconclusive” due to findings on clinical benefit being too uncertain to allow for a clear determination of their magnitude; however, ICER found L-Glutamine most likely provides some clinical benefit.16
ICER reported that at the treatments’ current list prices, 21% of patients could be treated in a given year with crizanlizumab, and 16% could be treated with voxelotor before crossing ICER’s potential budget-impact threshold of $819 million per year.16
Pipeline Treatments Pharmaceutical companies such as Vertex Pharmaceuticals, bluebird bio, Sangamo Therapeutics, and CRISPR Therapeutics are investigating the use of gene therapies to treat SCD. Gene therapy involves genetically altering a patient’s own hematopoietic stem cells using CRISPR (clustered regularly interspaced short palindromic repeats) and a viral vector to boost the production of fetal hemoglobin. This research provides more options for patients with SCD and may even act as a functional cure.17, 18
The financial disparity in this demographic population can often make access to treatment difficult, which ultimately leads to poor health outcomes, disease complications, and increased costs.
THE FUTURE IS NOW
SUMMIT Learn more about
Sickle Cell Disease Register for the 2020 Specialty Summit to access on-demand content featuring an interview with Dr. Ify Osunkwo, M.D., MPH, a sickle cell disease specialist at the Levine Cancer Institute. magellanrx.com/specialtysummit
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SICKLE CELL DISEASE | Continued
Managed Care Implications SCD presents a significant burden on the U.S. healthcare system. The majority of the SCD patient population is of African descent and on Medicaid or Medicare. The financial disparity in this demographic population can often make access to treatment difficult, which ultimately leads to poor health outcomes, disease complications, and increased costs.19
approved for SCD, chronic medical complications remain a burden. Ensuring appropriate use of therapies, including optimizing care before moving to these new medications, is important because of the high associated costs. Additionally, because Adakveo® is an intravenous infusion that requires administration by a healthcare professional, access may be difficult for many patients.
Most SCD patients today are not being treated appropriately due to the underutilization of current therapies. Emerging therapies present an opportunity to provide more-effective management of SCD, reducing VOCs and, ultimately, ED visits and healthcare resource utilization. However, although there are four medications
SCD is a lifelong disease; while bone marrow transplant is a complex treatment and finding a match is difficult, it remains the only potential cure for SCD. Gene therapies on the horizon show promising curative potential for SCD, which will undoubtedly impact patients and the healthcare system as they become a reality.
“Sickle Cell Disease (SCD).” Centers for Disease Control and Prevention, Oct. 21, 2019, https://www.cdc.gov/ncbddd/sicklecell/ data.html. Azevedo, Margarida. “Report Highlights Challenges of Sickle Cell Disease in Treatment, Access to Care.” Sickle Cell Disease News, Nov. 1, 2016, https://sicklecellanemianews.com/2016/11/01/ report-highlights-challenges-sickle-cell-disease-treatment-accesscare/. Fingar, Kathryn et al. “Characteristics of inpatient hospital stays involving sickle cell disease, 2000-2016.” Healthcare Cost and Utilization Project, Sept. 2019, https://hcup-us.ahrq.gov/reports/ statbriefs/sb251-Sickle-Cell-Disease-Stays-2016.jsp. “National Center for Health Statistics Web Tables.” Centers for Disease Control and Prevention, Apr. 3, 2020, https://www.cdc.gov/ nchs/ahcd/ahcd_products.htm. Field, Joshua J. “Five lessons learned about long-term pain management in adults with sickle cell disease.” American Society of Hematology Education Program. Hematology, Dec. 8, 2017, https://doi.org/10.1182/asheducation-2017.1.406.
“Sickle Cell Disease (SCD): Complications and Treatments of Sickle Cell Disease.” Centers for Disease Control and Prevention, Oct. 21, 2019, https://www.cdc.gov/ncbddd/sicklecell/treatments.html#.
Agrawal, Rohit Kumar et al. “Hydroxyurea in Sickle Cell Disease: Drug Review.” Indian Journal of Hematology and Blood Transfusion, May 24, 2013, https://doi.org/10.1007/s12288-013-0261-4.
McGann, Patrick T. and Russell E. Ware. “Hydroxyurea therapy for sickle cell anemia.” Expert Opinion on Drug Safety, pp. 1749-1758, Sept. 14, 2015, https://doi.org/10.1517/14740338.2015.1088827.
Al-Salem, Ahmed. “Hydroxyurea Treatment for Sickle Cell Anemia.” Medical and Surgical Complications of Sickle Cell Anemia, pp. 329–337, Dec. 15, 2015, https://doi.org/10.1007/978-3-31924762-5_21.
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10. Endari [package insert]. Torrance (CA): Emmaus Medical Inc; 2017. 11. Ballas, Samir K. et al. “The effect of iron chelation therapy on overall survival in sickle cell disease and β-thalassemia: A systematic review.” American Journal of Hematology, April 10, 2018, https:// doi.org/10.1002/ajh.25103. 12. Adakveo® [package insert]. East Hanover, NJ: Novartis Pharmaceuticals; 2019. 13. Oxbryta™ [package insert]. San Francisco, CA: Global Blood Therapeutics; 2019. 14. Kutlar, Abdullah. “Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: A SUSTAIN study analysis.” American Journal of Hematology, Oct. 8, 2018, https://doi. org/10.1002/ajh.25308. 15. Vichinsky, Elliott et al. “A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease.” The New England Journal of Medicine, Aug. 8, 2019, https://doi.org/10.1056/nejmoa1903212. 16. “Crizanlizumab, Voxelotor, and L-Glutamine for Sickle Cell Disease: Effectiveness and Value.” Institute for Clinical and Economic Review, March 12, 2020, https://icer-review.org/wp-content/ uploads/2019/08/ICER_SCD_Evidence-Report_031220.pdf. 17. “NIH researchers create new viral vector for improved gene therapy in sickle cell disease.” National Institutes of Health, Oct. 2, 2019, https://www.nhlbi.nih.gov/news/2019/nih-researchers-create-newviral-vector-improved-gene-therapy-sickle-cell-disease. 18. “Gene Therapy.” Sickle Cell Disease News, https:// sicklecellanemianews.com/gene-therapy/. 19. Lee, LaTasha et al. “Reducing health care disparities in sickle cell disease: A review.” Public Health Reports, Nov./Dec. 2019, https:// doi.org/10.1177/0033354919881438.
Method Capability Spotlight: Health Economics and Outcomes Research
Considering the high rate of ED visits among adults with diabetes, the Magellan Method team evaluated the potential need for more effective management of ED use in this population. In spring 2020, Magellan Method virtually presented research with the Academy of Managed Care Pharmacy (AMCP) highlighting health economics and outcomes research (HEOR) around the classification of Type 2 diabetes (T2DM) patients. The Magellan Method HEOR team focused on the New York University Emergency Department Algorithm (EDA), which is a tool that can be used to classify emergency department (ED) visits. The EDA is used to determine the emergent nature of ED visits based on full chart review and assesses information on patient complaints, symptoms, vital signs, diagnoses, procedures, and ED resource use.1 Considering the high rate of ED visits among adults over 45 years with diabetes â&#x20AC;&#x201D; who account for an estimated 12 million visits a year â&#x20AC;&#x201D; the Method team aimed to evaluate the potential need for more-effective management of ED use in this population. In this study, Magellan Method sought to assess the association of emergent classification of an ED visit based on the modified EDA with hospital admissions in T2DM patients.
Methods In order to achieve this objective, the team conducted a retrospective analysis of two commercial claims made by adult T2DM patients within the study period. The modified EDA categorized ED visits into three levels: emergent, intermediate, and nonemergent. The study focused on specific outcomes, including healthcare resource utilization and proportion of patients with ED visits or hospitalizations within 24 months before or after the study period.
Findings Of the 6,428 patients who met the inclusion criteria, 3.4%, 0.5%, and 7.6% of the patients had emergent, intermediate, and nonemergent ED visits, respectively, in the pre-index period, compared to 5.8%, 0.82%, and 11%, respectively, in the post-index period. The results were notable: The EDA measure of emergent ED visits was significantly associated with hospitalizations in the period before diagnosis (odds ratio [OR]: 1.82, 95% confidence interval [CI], 1.28-2.58) and in the period after diagnosis (OR: 1.48, 95% CI, 1.13-1.94) compared to those with nonemergent visits. As a tool, the EDA can be used to assess trends in ED utilization and can be used by health plans for intervention assessment. See Tables 1-4 and Figure 1 for an illustration of the methodology and results. The full AMCP poster presentation can be found at: https://www1.magellanrx.com/read-watch-listen/read/ clinical-research/.
HEOR Capabilities Utilizing real-world health-plan medical and pharmacy claims data, Method HEOR is able to quantify the clinical and economic needs for proposed partnership interventions such as assessing ED trends and interventions for patients with various disease states, with the goal of reducing ED use for nonemergent conditions while improving outcomes. In addition to the analysis completed in this study, Method HEOR has a range of capabilities providing innovative solutions to pharmaceutical partnersâ&#x20AC;&#x2122; needs. Many past Method HEOR projects have been award-winning presentations at industry
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HEOR SPOTLIGHT | Continued
Table 1. Patient Attrition Measure
Proportion of Total Members
A diagnosis of Type 2 diabetes: Jan. 1, 2017-June 30, 2019 (index)
With ≥2 diabetes diagnosis claims
Age ≥18 years on the index date
Commercial members only
Continuously enrolled in both medical and pharmacy benefits ≥24 months pre- and post-index
No other diabetes claims ≥24 months pre-index
Final study population
Table 2. Patient Demographics and Clinical Characteristics
Table 3. Emergency Department Use and Hospitalizations
Age at Index in Years, Mean (SD) [Median] Gender (n,%)
Pre-Index Deyo-Charlson Comorbidity Index Score (n,%)
Post-Index Deyo-Charlson Comorbidity Index Score, Mean (SD) [Median]
Post-Index Deyo-Charlson Comorbidity Index Score (n,%)
53.0 (9.68) [54.00]
2,305 (36.89) 2.55 (2.23) 
conferences such as the AMCP. Research and reporting capabilities offered by Method HEOR include predictive and budget-impact modeling; product utilization reviews, cost assessment evaluation, and trend prescription; clinical and financial impact of programs or policies; reduction in negative health outcomes; adherence and persistence and related effects; patient-reported outcomes; and publication planning and abstract or poster submissions.
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Proportion of Study Population
0.67 (1.42) 
Post-Index Deyo-Charlson Comorbidity Index Score, Mean (SD) [Median]
To learn more about Magellan Method and solution offerings, visit magellanrx.com/method.
Table 4. Regression: Predictors of Hospitalization Pre-Index
OR (95% CI)
OR (95% CI)
Deyo-Charlson Comorbidity Index Score
Emergency Department Status
This table estimates the association between EDA visit classification and hospitalization. OR = odds ratio; ref = reference variable
Figure 1. NYU Algorithm for Classifying Diagnoses2
PNE + PPCT + PEPA + PENPA = 100% Diagnoses Not Included • • • •
Mental health Alcohol Substance abuse Unclassiﬁed
ED Visit with an ICD-9/10
ED Care Needed
Primary-Care Treatable PPCT
Not Preventable/ Avoidable PENPA Preventable/ Avoidable PEPA
Gandhi, Sabina Ohri and Lindsay Sabik. “Emergency department visit classification using the NYU algorithm.” American Journal of Managed Care, April 20, 2014, https://www.ncbi.nlm.nih.gov/ pubmed/24884862.
Ballard, Dustin W. et al. “Validation of an Algorithm for Categorizing the Severity of Hospital Emergency Department Visits.” Medical Care 48 (1): 58–63, https://doi.org/10.1097/MLR.0b013e3181bd49ad. https://www.ncbi.nlm.nih.gov/pubmed/24884862.
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Not actual patients.
Indications and Usage
Saxenda® (liraglutide) injection 3 mg is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg/m2 or greater (obesity) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (eg, hypertension, type 2 diabetes mellitus, or dyslipidemia)
Limitations of Use
• Saxenda® is not indicated for the treatment of type 2 diabetes • Saxenda® and Victoza® both contain the same active ingredient, liraglutide, and therefore should not be used together. Saxenda® should not be used in combination with any other GLP-1 receptor agonist • Saxenda® has not been studied in patients taking insulin. Saxenda® and insulin should not be used together • The safety and efficacy of Saxenda® in combination with other products for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established
Important Safety Information WARNING: RISK OF THYROID C-CELL TUMORS
Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined. Saxenda® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Saxenda® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Saxenda®.
Saxenda® is contraindicated in: • Patients with a personal or family history of MTC or MEN 2 • Patients with a prior serious hypersensitivity reaction to liraglutide or to any of the product components • Pregnancy
Warnings and Precautions • Risk of Thyroid C-cell Tumors: If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated • Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with liraglutide postmarketing. Observe patients carefully for signs and symptoms of pancreatitis (persistent severe abdominal pain, sometimes radiating to the back with or without vomiting). If pancreatitis is suspected, discontinue Saxenda® promptly and if pancreatitis is confirmed, do not restart • Acute Gallbladder Disease: Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in patients treated with Saxenda® than with placebo even after accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
WHEN IT COMES TO LOSING WEIGHT AND KEEPING IT OFF
WE HAVE THE
NOW YOU CAN GIVE US THE
Give them the power to choose a way forward by adding Saxenda®. To manage the chronic disease of obesity, willpower alone isn’t enough. Combined with a reduced-calorie meal plan and increased physical activity, Saxenda® can help patients lose weight and keep it off.1 When patients with obesity lose weight, one response of their bodies involves an increase in the hunger hormone, and a decrease in satiety hormones including glucagon-like peptide (GLP-1)—undermining their ability to lose weight and keep it off.2 Saxenda®, which is 97% similar to the native gut hormone GLP-1, activates receptors in the braina to increase satiety and thereby reduce food intake.1,a Half of patients taking Saxenda® who achieved ≥5% body weight loss at 1 year maintained it at 3 years in a 3-year study (vs 25% and 10% for placebo, respectively).1,b —————— In a cardiovascular outcomes (CVOT) trial, NO increased risk of MACE observed with liraglutide 1.8 mg in patients with type 2 diabetes and cardiovascular disease.1,c Rate of primary component MACE endpoints was 1302 (608 [13.0%] with liraglutide 1.8 mg and 694 [14.9%] with placebo). Efficacy of doses below 3 mg has not been established for chronic weight management.
People living with obesity want you to ask them about their weight-loss attempts. Tell them how adding Saxenda® can help them lose weight and keep it off.
Shown in animal models.1 A 160-week, randomized, double-blind, placebo-controlled study that evaluated the percentage of patients who achieved ≥5% weight loss at both 1 and 3 years. Adults with pre-diabetes and a BMI of ≥30 or ≥27 with at least one weight-related comorbidity were randomized to receive once-daily Saxenda® (n=1,505) or placebo (n=749), added to lifestyle intervention, including increased physical activity and a 500-kcal/day-deficit diet. Study included: 4 weeks of dose escalation; 156 weeks at full dose; and 12-week off-drug observational period. Mean baseline body weight was 233.9 lb; mean BMI was 38.3. 817 Saxenda® patients vs 182 on placebo, and 391 patients on Saxenda® and 74 on placebo lost ≥5% at 1 and 3 years, respectively.1,3 c Major Adverse Cardiovascular Event (MACE) defined as: cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Results from a randomized trial of 9340 patients with inadequately controlled type 2 diabetes and cardiovascular disease treated with liraglutide 1.8 mg or placebo in addition to standard of care treatments for type 2 diabetes for a median duration of 3.5 years. Patients either were 50 years of age or older with established, stable cardiovascular, cerebrovascular, peripheral vascular disease, chronic renal failure or chronic heart failure (80% of patients), or were 60 years of age or older and had other specified risk factors of vascular disease (20% of patients). The primary endpoint was the time from randomization to first occurrence of a major adverse cardiovascular event. 96.8% of the patients completed the trial.1 a
Important Safety Information (cont’d) • Risk of Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy: When Saxenda® is used with an insulin secretagogue (eg, a sulfonylurea) serious hypoglycemia can occur. Consider lowering the dose of the insulin secretagogue to reduce the risk of hypoglycemia. Monitor blood glucose parameters prior to starting Saxenda® and during treatment and adjust anti-diabetic drugs as needed • Heart Rate Increase: Mean increases in resting heart rate of 2 to 3 beats per minute (bpm) were observed in patients treated with Saxenda®. Monitor heart rate at regular intervals and inform patients to report palpitations or feelings of a racing heartbeat while at rest during treatment with Saxenda®. Discontinue Saxenda® in patients who experience a sustained increase in resting heart rate • Renal Impairment: Acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis, have been reported, usually in association with nausea, vomiting, diarrhea, or dehydration. Use caution when initiating or escalating doses of Saxenda® in patients with renal impairment • Hypersensitivity Reactions: Serious hypersensitivity reactions (eg, anaphylaxis and angioedema) have been reported in patients treated with liraglutide. If a hypersensitivity reaction occurs, patients should stop taking Saxenda® and promptly seek medical advice • Suicidal Behavior and Ideation: In clinical trials, 9 (0.3%) of 3,384 patients treated with Saxenda® and 2 (0.1%) of the 1,941 treated with placebo reported suicidal ideation; one of the patients treated with Saxenda® attempted suicide. Monitor patients on Saxenda® for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue treatment if patients experience suicidal thoughts or behaviors. Avoid Saxenda® in patients with a history of suicidal attempts or active suicidal ideation
• The most common adverse reactions, reported in ≥5% are: nausea, hypoglycemia, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, and increased lipase
• Saxenda® causes a delay of gastric emptying, and has the potential to impact the absorption of concomitantly administered oral medications. Monitor for potential consequences of delayed absorption of oral medications concomitantly administered with Saxenda®
Use in Specific Populations
• There are no data on the presence of liraglutide in human breast milk; liraglutide was present in the milk of lactating rats • Saxenda® has not been studied in patients below 18 years of age and is not recommended for use in pediatric patients • Saxenda® slows gastric emptying. Saxenda® has not been studied in patients with preexisting gastroparesis
Please see Brief Summary of Information about Saxenda® on the following pages. References 1. Saxenda® [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2018. 2. Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365(17):1597-1604. 3. le Roux CW, Astrup A, Fujioka K, et al; for the SCALE Obesity and Prediabetes NN8022-1839 Study Group. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial [published online February 22, 2017]. Lancet. doi:10.1016/S0140-6736(17)30069-7. Saxenda® and Victoza® are registered trademarks of Novo Nordisk A/S. Novo Nordisk is a registered trademark of Novo Nordisk A/S. © 2020 Novo Nordisk Printed in the U.S.A. US20SX00016 March 2020
Saxenda® (liraglutide) injection Rx Only BRIEF SUMMARY. Please consult package insert for full prescribing information. WARNING: RISK OF THYROID C-CELL TUMORS: Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions]. Saxenda® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Saxenda® and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Saxenda® [see Contraindications, Warnings and Precautions]. INDICATIONS AND USAGE: Saxenda® is indicated as an adjunct to a reducedcalorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg/m2 or greater (obese), or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia). Limitations of Use: Saxenda® is not indicated for the treatment of type 2 diabetes mellitus. Saxenda® and Victoza® both contain the same active ingredient, liraglutide, and therefore should not be used together. Saxenda® should not be used in combination with any other GLP-1 receptor agonist. Saxenda® has not been studied in patients taking insulin. Saxenda® and insulin should not be used together [see Warnings and Precautions]. The safety and effectiveness of Saxenda® in combination with other products intended for weight loss, including prescription drugs, over-thecounter drugs, and herbal preparations, have not been established. CONTRAINDICATIONS: Saxenda® is contraindicated in: Patients with a personal or family history of medullary thyroid carcinoma (MTC) or patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings and Precautions]; Patients with a prior serious hypersensitivity reaction to liraglutide or to any of the product components [see Warnings and Precautions]; Pregnancy [see Use in Specific Populations]. WARNINGS AND PRECAUTIONS: Risk of Thyroid C-cell Tumors: Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors (adenomas and/or carcinomas) at clinically relevant exposures in both genders of rats and mice. Malignant thyroid C-cell carcinomas were detected in rats and mice. It is unknown whether Saxenda® will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined. Cases of MTC in patients treated with liraglutide have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and liraglutide use in humans. Saxenda ® is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of Saxenda® and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Saxenda ®. Such monitoring may increase the risk of unnecessary procedures, due to low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin may indicate MTC, and patients with MTC usually have calcitonin values greater than 50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated. Acute Pancreatitis: Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with liraglutide. After initiation of Saxenda®, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, Saxenda® should promptly be discontinued and appropriate management should be initiated. If pancreatitis is confirmed, Saxenda® should not be restarted. In Saxenda® clinical trials, acute pancreatitis was confirmed by adjudication in 9 (0.3%) of 3291 Saxenda-treated patients and 2 (0.1%) of 1843 placebo-treated patients. In addition, there were 2 cases of acute pancreatitis in Saxenda-treated patients who prematurely withdrew from these clinical trials, occurring 74 and 124 days after the last dose. There were 2 additional cases in Saxenda-treated patients, 1 during an off-treatment follow-up period within 2 weeks of discontinuing Saxenda ®, and 1 that occurred in a patient who completed treatment and was off-treatment for 106 days. Liraglutide has been studied in a limited number of patients with a history of pancreatitis. It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on Saxenda®. Acute Gallbladder Disease: In Saxenda® clinical
trials, 2.2% of Saxenda-treated patients reported adverse events of cholelithiasis versus 0.8% of placebo-treated patients. The incidence of cholecystitis was 0.8% in Saxenda-treated patients versus 0.4% in placebo-treated patients. The majority of Saxenda-treated patients with adverse events of cholelithiasis and cholecystitis required cholecystectomy. Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in Saxenda-treated patients than in placebo-treated patients even after accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated. Risk for Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy: The risk for serious hypoglycemia is increased when Saxenda® is used in combination with insulin secretagogues (for example, sulfonylureas) in patients with type 2 diabetes mellitus. Therefore, patients may require a lower dose of sulfonylurea (or other concomitantly administered insulin secretagogues) in this setting [see Adverse Reactions]. Saxenda® should not be used in patients taking insulin. Saxenda® can lower blood glucose. Monitor blood glucose parameters prior to starting Saxenda® and during Saxenda® treatment in patients with type 2 diabetes. If needed, adjust co-administered anti-diabetic drugs based on glucose monitoring results and risk of hypoglycemia. Heart Rate Increase: Mean increases in resting heart rate of 2 to 3 beats per minute (bpm) were observed with routine clinical monitoring in Saxenda-treated patients compared to placebo in clinical trials. More patients treated with Saxenda ®, compared with placebo, had changes from baseline at two consecutive visits of more than 10 bpm (34% versus 19%, respectively) and 20 bpm (5% versus 2%, respectively). At least one resting heart rate exceeding 100 bpm was recorded for 6% of Saxenda-treated patients compared with 4% of placebo-treated patients, with this occurring at two consecutive study visits for 0.9% and 0.3%, respectively. Tachycardia was reported as an adverse reaction in 0.6% of Saxenda-treated patients and in 0.1% of placebo-treated patients. In a clinical pharmacology trial that monitored heart rate continuously for 24 hours, Saxenda® treatment was associated with a heart rate that was 4 to 9 bpm higher than that observed with placebo. Heart rate should be monitored at regular intervals consistent with usual clinical practice. Patients should inform health care providers of palpitations or feelings of a racing heartbeat while at rest during Saxenda ® treatment. For patients who experience a sustained increase in resting heart rate while taking Saxenda®, Saxenda® should be discontinued. Renal Impairment: In patients treated with GLP-1 receptor agonists, including Saxenda®, there have been reports of acute renal failure and worsening of chronic renal failure, sometimes requiring hemodialysis [see Adverse Reactions]. Some of these events were reported in patients without known underlying renal disease. A majority of the reported events occurred in patients who had experienced nausea, vomiting, or diarrhea leading to volume depletion. Some of the reported events occurred in patients receiving one or more medications known to affect renal function or volume status. Altered renal function has been reversed in many of the reported cases with supportive treatment and discontinuation of potentially causative agents, including liraglutide. Use caution when initiating or escalating doses of Saxenda® in patients with renal impairment [see Use in Specific Populations]. Hypersensitivity Reactions: There have been reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in patients treated with liraglutide [see Contraindications and Adverse Reactions]. If a hypersensitivity reaction occurs, the patient should discontinue Saxenda® and other suspect medications and promptly seek medical advice. Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to these reactions with Saxenda®. Suicidal Behavior and Ideation: In Saxenda® clinical trials, 9 (0.3%) of 3384 Saxenda-treated patients and 2 (0.1%) of the 1941 placebo-treated patients reported suicidal ideation; one of these Saxenda-treated patients attempted suicide. Patients treated with Saxenda® should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue Saxenda ® in patients who experience suicidal thoughts or behaviors. Avoid Saxenda® in patients with a history of suicidal attempts or active suicidal ideation. ADVERSE REACTIONS: The following serious adverse reactions are described below or elsewhere in the prescribing information: Risk of Thyroid C-Cell Tumors [see Warnings and Precautions]; Acute Pancreatitis [see Warnings and Precautions]; Acute Gallbladder Disease [see Warnings and Precautions]; Risk for Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy [see Warnings and Precautions]; Heart Rate Increase [see Warnings and Precautions]; Renal Impairment [see Warnings and Precautions]; Hypersensitivity Reactions [see Warnings and Precautions]; Suicidal Behavior and Ideation [see Warnings and Precautions]. Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Saxenda® was evaluated for safety in 5 double-blind, placebo controlled trials that included 3384 overweight or obese patients treated with Saxenda® for a treatment period up to 56 weeks (3 trials), 52 weeks (1 trial), and 32 weeks (1 trial). All patients received study drug in addition to diet and exercise counseling. In these trials, patients received Saxenda® for a mean treatment duration of 46 weeks (median, 56 weeks). Baseline characteristics included a mean age of 47 years, 71% women, 85% white, 39% with hypertension, 15% with type 2 diabetes, 34% with dyslipidemia, 29% with a BMI greater than 40 kg/m2, and 9% with cardiovascular disease. In one of the 56-week trials, a subset of patients (with abnormal glucose measurements at randomization) were enrolled for a placebo-
controlled 160-week period instead, followed by a 12-week off-treatment follow-up. For those participating in this 160-week period, patients received Saxenda® for a mean treatment duration of 110 weeks (median, 159 weeks). For all trials, dosing was initiated and increased weekly to reach the 3 mg dose. In clinical trials, 9.8% of patients treated with Saxenda® and 4.3% of patients treated with placebo prematurely discontinued treatment as a result of adverse reactions. The most common adverse reactions leading to discontinuation were nausea (2.9% versus 0.2% for Saxenda® and placebo, respectively), vomiting (1.7% versus less than 0.1%), and diarrhea (1.4% versus 0%). Adverse reactions reported in greater than or equal to 2% of Saxenda-treated patients and more frequently than in placebo-treated patients are shown in Table 3. Table 3. Adverse Reactions Reported in Greater Than or Equal to 2% of Saxenda-treated Patients and More Frequently than with Placebo* Placebo Saxenda N = 1941 N = 3384 % % Gastrointestinal Disorders Nausea 13.8 39.3 Diarrhea 9.9 20.9 Constipation 8.5 19.4 Vomiting 3.9 15.7 Dyspepsia 2.7 9.6 Abdominal Pain 3.1 5.4 Upper Abdominal Pain 2.7 5.1 Gastroesophageal Reflux Disease 1.7 4.7 Abdominal Distension 3.0 4.5 Eructation 0.2 4.5 Flatulence 2.5 4.0 Dry Mouth 1.0 2.3 Metabolism and Nutrition Disorders 12.7 23.0 Hypoglycemia in T2DM1 Decreased Appetite 2.3 10.0 Nervous System Disorders Headache 12.6 13.6 Dizziness 5.0 6.9 General Disorders and Administration Site Conditions Fatigue 4.6 7.5 Injection Site Erythema 0.2 2.5 Injection Site Reaction 0.6 2.5 Asthenia 0.8 2.1 Infections and Infestations Gastroenteritis 3.2 4.7 Urinary Tract Infection 3.1 4.3 Viral Gastroenteritis 1.6 2.8 Investigations Increased Lipase 2.2 5.3 Psychiatric Disorders Insomnia 1.7 2.4 Anxiety 1.6 2.0 1 Documented symptomatic (defined as documented symptoms of hypoglycemia in combination with a plasma glucose less than or equal to 70 mg/dL) in patients with type 2 diabetes (Study 2). See text below for further information regarding hypoglycemia in patients with and without type 2 diabetes. T2DM = type 2 diabetes mellitus * Adverse reactions for trials with treatment period up to 56 weeks Hypoglycemia: Saxenda® can lower blood glucose. In a clinical trial involving patients with type 2 diabetes mellitus and overweight or obesity, severe hypoglycemia (defined as requiring the assistance of another person) occurred in 3 (0.7%) of 422 Saxenda-treated patients and in none of the 212 placebo-treated patients. Each of these 3 Saxenda-treated patients was also taking a sulfonylurea. In the same trial, among patients taking a sulfonylurea, documented symptomatic hypoglycemia (defined as documented symptoms of hypoglycemia in combination with a plasma glucose less than or equal to 70 mg/dL) occurred in 48 (43.6%) of 110 Saxendatreated patients and 15 (27.3%) of 55 placebo-treated patients. The doses of sulfonylureas were reduced by 50% at the beginning of the trial per protocol. The frequency of hypoglycemia may be higher if the dose of sulfonylurea is not reduced. Among patients not taking a sulfonylurea, documented symptomatic hypoglycemia occurred in 49 (15.7%) of 312 Saxenda-treated patients and 12 (7.6%) of 157 placebo-treated patients. In Saxenda ® clinical trials involving patients without type 2 diabetes mellitus, there was no systematic capturing or reporting of hypoglycemia, as patients were not provided with blood glucose meters or hypoglycemia diaries. Spontaneously reported symptomatic episodes of unconfirmed hypoglycemia were reported by 46 (1.6%) of 2962 Saxenda-treated patients and 19 (1.1%) of 1729 placebo-treated patients. Fasting plasma glucose values obtained at routine clinic visits less than or equal to 70 mg/dL, irrespective of hypoglycemic symptoms, were
reported as “hypoglycemia” in 92 (3.1%) Saxenda-treated patients and 13 (0.8%) placebo-treated patients. Gastrointestinal Adverse Reactions: In the clinical trials, approximately 68% of Saxenda-treated patients and 39% of placebo-treated patients reported gastrointestinal disorders; the most frequently reported was nausea (39% and 14% of patients treated with Saxenda® and placebo, respectively). The percentage of patients reporting nausea declined as treatment continued. Other common adverse reactions that occurred at a higher incidence among Saxendatreated patients included diarrhea, constipation, vomiting, dyspepsia, abdominal pain, dry mouth, gastritis, gastroesophageal reflux disease, flatulence, eructation and abdominal distension. Most episodes of gastrointestinal events were mild or moderate and did not lead to discontinuation of therapy (6.2% with Saxenda® versus 0.8% with placebo discontinued treatment as a result of gastrointestinal adverse reactions). There have been reports of gastrointestinal adverse reactions, such as nausea, vomiting, and diarrhea, associated with volume depletion and renal impairment [see Warnings and Precautions]. Asthenia, Fatigue, Malaise, Dysgeusia and Dizziness: Events of asthenia, fatigue, malaise, dysgeusia and dizziness were mainly reported within the first 12 weeks of treatment with Saxenda ® and were often co-reported with gastrointestinal events such as nausea, vomiting, and diarrhea. Immunogenicity: Patients treated with Saxenda® may develop anti-liraglutide antibodies. Anti-liraglutide antibodies were detected in 42 (2.8%) of 1505 Saxendatreated patients with a post-baseline assessment. Antibodies that had a neutralizing effect on liraglutide in an in vitro assay occurred in 18 (1.2%) of 1505 Saxendatreated patients. Presence of antibodies may be associated with a higher incidence of injection site reactions and reports of low blood glucose. In clinical trials, these events were usually classified as mild and resolved while patients continued on treatment. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, the incidence of antibodies to Saxenda® cannot be directly compared with the incidence of antibodies of other products. Allergic Reactions: Urticaria was reported in 0.7% of Saxenda-treated patients and 0.5% of placebo-treated patients. Anaphylactic reactions, asthma, bronchial hyperreactivity, bronchospasm, oropharyngeal swelling, facial swelling, angioedema, pharyngeal edema, type IV hypersensitivity reactions have been reported in patients treated with liraglutide in clinical trials. Cases of anaphylactic reactions with additional symptoms such as hypotension, palpitations, dyspnea, and edema have been reported with marketed use of liraglutide. Anaphylactic reactions may potentially be life-threatening. Injection Site Reactions: Injection site reactions were reported in approximately 13.9% of Saxenda-treated patients and 10.5% of placebo-treated patients. The most common reactions, each reported by 1% to 2.5% of Saxenda-treated patients and more commonly than by placebo-treated patients, included erythema, pruritus, and rash at the injection site. 0.6% of Saxenda-treated patients and 0.5% of placebo-treated patients discontinued treatment due to injection site reactions. Breast Cancer: In Saxenda® clinical trials, breast cancer confirmed by adjudication was reported in 17 (0.7%) of 2379 Saxendatreated women compared with 3 (0.2%) of 1300 placebo-treated women, including invasive cancer (13 Saxenda- and 2 placebo-treated women) and ductal carcinoma in situ (4 Saxenda- and 1 placebo-treated woman). The majority of cancers were estrogen- and progesterone-receptor positive. There were too few cases to determine whether these cases were related to Saxenda®. In addition, there are insufficient data to determine whether Saxenda® has an effect on pre-existing breast neoplasia. Papillary Thyroid Cancer: In Saxenda® clinical trials, papillary thyroid carcinoma confirmed by adjudication was reported in 8 (0.2%) of 3291 Saxenda-treated patients compared with no cases among 1843 placebo-treated patients. Four of these papillary thyroid carcinomas were less than 1 cm in greatest diameter and 4 were diagnosed in surgical pathology specimens after thyroidectomy prompted by findings identified prior to treatment. Colorectal Neoplasms: In Saxenda® clinical trials, benign colorectal neoplasms (mostly colon adenomas) confirmed by adjudication were reported in 20 (0.6%) of 3291 Saxenda-treated patients compared with 7 (0.4%) of 1843 placebo-treated patients. Six positively adjudicated cases of malignant colorectal neoplasms were reported in 5 Saxenda-treated patients (0.2%, mostly adenocarcinomas) and 1 in a placebo-treated patient (0.1%, neuroendocrine tumor of the rectum). Cardiac Conduction Disorders: In Saxenda® clinical trials, 11 (0.3%) of 3384 Saxenda-treated patients compared with none of the 1941 placebotreated patients had a cardiac conduction disorder, reported as first degree atrioventricular block, right bundle branch block, or left bundle branch block. Hypotension: Adverse reactions related to hypotension (that is, reports of hypotension, orthostatic hypotension, circulatory collapse, and decreased blood pressure) were reported more frequently with Saxenda ® (1.1%) compared with placebo (0.5%) in Saxenda® clinical trials. Systolic blood pressure decreases to less than 80 mmHg were observed in 4 (0.1%) Saxenda-treated patients compared with no placebo-treated patients. One of the Saxenda-treated patients had hypotension associated with gastrointestinal adverse reactions and renal failure [see Warnings and Precautions]. Laboratory Abnormalities: Liver Enzymes: Increases in alanine aminotransferase (ALT) greater than or equal to 10 times the upper limit of normal were observed in 5 (0.15%) Saxenda-treated patients (two of whom had ALT greater than 20 and 40 times the upper limit of normal) compared with 1 (0.05%) placebotreated patient during the Saxenda® clinical trials. Because clinical evaluation to exclude alternative causes of ALT and aspartate aminotransferase (AST) increases was not done in most cases, the relationship to Saxenda® is uncertain. Some
increases in ALT and AST were associated with other confounding factors (such as gallstones). Serum Calcitonin: Calcitonin, a biological marker of MTC, was measured throughout the clinical development program [see Warnings and Precautions]. More patients treated with Saxenda® in the clinical trials were observed to have high calcitonin values during treatment, compared with placebo. The proportion of patients with calcitonin greater than or equal to 2 times the upper limit of normal at the end of the trial was 1.2% in Saxenda-treated patients and 0.6% in placebo-treated patients. Calcitonin values greater than 20 ng/L at the end of the trial occurred in 0.5% of Saxenda-treated patients and 0.2% of placebo-treated patients; among patients with pre-treatment serum calcitonin less than 20 ng/L, none had calcitonin elevations to greater than 50 ng/L at the end of the trial. Serum Lipase and Amylase: Serum lipase and amylase were routinely measured in the Saxenda® clinical trials. Among Saxenda-treated patients, 2.1% had a lipase value at anytime during treatment of greater than or equal to 3 times the upper limit of normal compared with 1.0% of placebo-treated patients. 0.1% of Saxenda-treated patients had an amylase value at anytime in the trial of greater than or equal to 3 times the upper limit of normal versus 0.1% of placebo-treated patients. The clinical significance of elevations in lipase or amylase with Saxenda® is unknown in the absence of other signs and symptoms of pancreatitis [see Warnings and Precautions]. Post-Marketing Experience: The following adverse reactions have been reported during post-approval use of liraglutide, the active ingredient of Saxenda®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Neoplasms: Medullary thyroid carcinoma [see Warnings and Precautions]; Gastrointestinal Disorders: Acute pancreatitis, hemorrhagic and necrotizing pancreatitis, sometimes resulting in death [see Warnings and Precautions]; Metabolism and Nutrition Disorders: Dehydration resulting from nausea, vomiting and diarrhea [see Adverse Reactions]; Renal and Urinary Disorders: Increased serum creatinine, acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis [see Warnings and Precautions]; General Disorders and Administration Site Conditions: Allergic reactions: rash and pruritus [see Adverse Reactions]; Immune System Disorders: Angioedema and anaphylactic reactions [see Warnings and Precautions]; Hepatobiliary Disorders: Elevations of liver enzymes, hyperbilirubinemia, cholestasis and hepatitis [see Adverse Reactions] DRUG INTERACTIONS: Oral Medications: Saxenda® causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, liraglutide did not affect the absorption of the tested orally administered medications to any clinically relevant degree. Nonetheless, monitor for potential consequences of delayed absorption of oral medications concomitantly administered with Saxenda®. USE IN SPECIFIC POPULATIONS: Pregnancy: Risk Summary: Saxenda® is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm [see Clinical Considerations]. There are no available data with liraglutide in pregnant women to inform a drug associated risk for major birth defects and miscarriage. Saxenda® should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, treatment with Saxenda® should be discontinued. Animal reproduction studies identified increased adverse embryofetal developmental outcomes from exposure during pregnancy. Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 3 mg/day. In pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD [see Animal Data]. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations: Disease-associated maternal and/or embryofetal risk: A minimum weight gain, and no weight loss, is recommended for all pregnant women, including those who are already overweight or obese, due to the necessary weight gain that occurs in maternal tissues during pregnancy. Animal Data: Liraglutide has been shown to be teratogenic in rats at or above 0.8-times systemic exposures in obese humans resulting from the maximum recommended human dose (MRHD) of 3 mg/day based on plasma area under the time-concentration curve (AUC) comparison. Liraglutide has been shown to cause reduced growth and increased total major abnormalities in rabbits at systemic exposures below exposure in obese humans at the MRHD based on plasma AUC comparison. Female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the exposure in obese humans at the MRHD based on plasma AUC comparison. The number of early embryonic deaths in the 1 mg/kg/day group increased slightly. Fetal abnormalities and variations in kidneys and blood vessels, irregular ossification of the skull, and a more complete state of ossification occurred at all doses. Mottled liver and minimally kinked ribs occurred at the highest dose. The incidence of fetal malformations in liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or narrowed opening into larynx at 0.1 mg/kg/day and umbilical hernia at 0.1 and 0.25 mg/kg/day. Pregnant rabbits given subcutaneous doses of 0.01, 0.025 and 0.05 mg/kg/day liraglutide from gestation day 6 through day 18 inclusive, had estimated systemic exposures less than the exposure in obese
humans at the MRHD of 3 mg/day at all doses, based on plasma AUC comparison. Liraglutide decreased fetal weight and dose-dependently increased the incidence of total major fetal abnormalities at all doses. The incidence of malformations exceeded concurrent and historical controls at 0.01 mg/kg/day (kidneys, scapula), greater than or equal to 0.01 mg/kg/day (eyes, forelimb), 0.025 mg/kg/day (brain, tail and sacral vertebrae, major blood vessels and heart, umbilicus), greater than or equal to 0.025 mg/kg/day (sternum) and at 0.05 mg/kg/day (parietal bones, major blood vessels). Irregular ossification and/or skeletal abnormalities occurred in the skull and jaw, vertebrae and ribs, sternum, pelvis, tail, and scapula; and dose-dependent minor skeletal variations were observed. Visceral abnormalities occurred in blood vessels, lung, liver, and esophagus. Bilobed or bifurcated gallbladder was seen in all treatment groups, but not in the control group. In pregnant female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide from gestation day 6 through weaning or termination of nursing on lactation day 24, estimated systemic exposures were 0.8-, 3-, and 11-times exposure in obese humans at the MRHD of 3 mg/day, based on plasma AUC comparison. A slight delay in parturition was observed in the majority of treated rats. Group mean body weight of neonatal rats from liraglutide-treated dams was lower than neonatal rats from control group dams. Bloody scabs and agitated behavior occurred in male rats descended from dams treated with 1 mg/ kg/day liraglutide. Group mean body weight from birth to postpartum day 14 trended lower in F2 generation rats descended from liraglutide-treated rats compared to F2 generation rats descended from controls, but differences did not reach statistical significance for any group. Lactation: Risk Summary: There are no data on the presence of liraglutide in human milk, the effects on the breastfed infant, or effects on milk production. Liraglutide was present in the milk of lactating rats (see Data). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Saxenda® and any potential adverse effects on the breastfed infant from Saxenda® or from the underlying maternal condition. Data: In lactating rats, liraglutide was present unchanged in milk at concentrations approximately 50% of maternal plasma concentrations. Pediatric Use: Safety and effectiveness of Saxenda® have not been established in pediatric patients. Saxenda® is not recommended for use in pediatric patients. Geriatric Use: In the Saxenda® clinical trials, 232 (6.9%) of the Saxenda-treated patients were 65 years of age and over, and 17 (0.5%) of the Saxenda-treated patients were 75 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Renal Impairment: There is limited experience with Saxenda® in patients with mild, moderate, and severe renal impairment, including end-stage renal disease. However, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure with liraglutide, which may sometimes require hemodialysis [see Warnings and Precautions and Adverse Reactions]. Saxenda® should be used with caution in this patient population. Hepatic Impairment: There is limited experience in patients with mild, moderate, or severe hepatic impairment. Therefore, Saxenda® should be used with caution in this patient population. Gastroparesis: Saxenda® slows gastric emptying. Saxenda® has not been studied in patients with pre-existing gastroparesis. OVERDOSAGE: Overdoses have been reported in clinical trials and post-marketing use of liraglutide. Effects have included severe nausea and severe vomiting. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. More detailed information is available upon request.
Version: 5 Saxenda® and Victoza® are registered trademarks of Novo Nordisk A/S. PATENT Information: http://novonordisk-us.com/patients/products/productpatents.html Manufactured by: Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark For information about Saxenda® contact: Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ 08536 1-844-363-4448 © 2014-2018 Novo Nordisk US20SX00007 2/2020
Managing Obesity: Developing a Successful Weight-Management Program A comprehensive weight-management program providing access to varying treatment strategies can improve health outcomes for employees and economic outcomes for employers. In the spring 2020 Magellan Rx Report, we discussed gaps in employer weight-management program strategies. Here, we will explore the process of developing and implementing an effective employersponsored program.
Identifying Key Decision-Makers
Lindsay C. Speicher, J.D. Project Manager Magellan Method
It is crucial to identify benefit design decision-makers at the outset of program development, since they will have key insights into aspects of the employer organization’s culture and financial and logistical considerations that will influence the objectives, structure, evolution, and scope of the weightmanagement program. The decision to implement a weight-management program should include input from individuals within multiple areas of the employer organization — specifically those in human resources (HR) and any others who determine benefit design. Some employers have benefit-management teams with expertise in employer-sponsored programs and benefit design to research employee benefit options. In many other organizations, the employees charged with recommending benefit design have a broad range of responsibilities. When exploring various benefit programs — including weight-management initiatives — these individuals often reach out to benefit consultants and vendors with wellness program offerings to facilitate their understanding of their options. Whether they rely on external support or investigate coverage options independently, these employees will ultimately make recommendations for benefit coverage, which may include supplemental programs or services such as weight management and other “riders” (benefits offered in addition to basic health insurance coverage, typically at an additional cost) for employees and their dependents. Weight-management program developers can make insight sharing into program design and implementation gaps more effective by making it relevant to the decision-makers’ organization.
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MANAGING OBESITY | Continued
Organization-specific employee-population health information can provide context and support informed decision-making regarding the clinical and economic value of offering a comprehensive, proven weight-management program.
Organizational Structure and Benefit Design An effective weight-management program will present an intersection of medical benefits, pharmacy benefits, and employersponsored programs. In order to better understand how this type of program will work in a specific employer organization, weightmanagement program developers must conduct research and evaluate the organization’s structure. The exploration of the benefit design with regard to weight-management programs will require a detailed understanding of the current program, the coordination of the medical benefit and pharmacy benefit, and its corresponding fit within a broader employer-sponsored initiative. Decision-makers within the employer organization may have limited experience with effective weight-management programs and how such an initiative would align with the overall benefit structure, which may influence how weight-management programs are presented, reviewed, and considered. Limited information and time for inquiry, competing financial priorities, and still-emergent knowledge of weight-management challenges and obesity as a medical condition may lead organizations to choose only basic weightmanagement programs (such as those discussed in part one of this series) that primarily rely on surgical intervention. An expert panel discussion conducted by Magellan Rx Management in March 2017 and another in 2007 determined that successful wellness programs must be embedded in existing infrastructure, including benefit design.1, 2 According to a 2015 International Foundation of Employee Benefit Plans workplace wellness survey, about half of employers coordinated wellness incentives and penalties with employer-provided insurance plans, and employers most often tied incentives to benefit design through changes to premiums, copays, coinsurance, deductibles, or contributions to health savings accounts.2 Larger-scale incentives such as employee benefits can positively impact participation; companies that link wellness and weight-management programs with outcomes-based incentives report a 30% higher participation rate than those that do not.2 Historically, employer-sponsored wellness initiatives were considered a separate entity from employer-provided health plans, including medical and pharmacy benefits, but it is becoming more common for employers to combine them. This trend only became more prevalent with the Affordable Care Act, which, along with mandating employer coverage of preventive services, increased the limit on rewards that can be offered through a group health plan for completing wellness programs.2, 3
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Access to weight-management services may be challenged by financial constraints and competing organizational priorities. In the event there is employer interest and commitment to providing access to effective, multifaceted weight-management programs, decision-makers must take significant, proactive steps to explore the nature, scope, and potential strategies for integrating these services into the medical and pharmacy benefits. Decision-makers will work closely with their health plan to determine criteria, eligibility, and conditions around weight-management coverage. This step will likely be the most complicated in the process. Strategic planning and implementation are essential to ensuring the program’s success. Surveying employees regarding their specific health interests and concerns, comparing plan options with employee needs in mind, and analyzing organizational financial capacity are important first steps.2 Successful implementation will rely heavily on employee education, since without comprehensive knowledge of the benefits available to them, employees cannot take full advantage of wellness initiatives.2
Value-Based Benefit Design Value-based benefit design (VBBD), a relatively new approach to health insurance, allows for lower copayments and costs for high-value clinical services.1 Employees may benefit from educational efforts, as many large employers are implementing this approach in order to control healthcare spending. As of September 2015, about a third of large employers offered financial incentives to employees who opted to participate in wellness programs, including obesity-management or weight-loss programs.4 Under VBBD, health plans or employers must develop a benefits package that incentivizes members or employees to see providers who have proven success in patient weight control.5 Employers have the ability to manage employees’ treatment strategies by reducing copayments on proven-effective therapies and increasing cost on therapies of lower value.6 The most favorable VBBD outcomes occur when both patients and providers are committed to the weight-management process and employers effectively engage with health plans to develop performance-based provider networks and negotiate performance-based rates.5 In terms of weight management, VBBD’s true value is long-term, as this benefit structure drives employees toward treatments and therapies that are proven to be effective and that will produce the longterm outcomes employees strive to achieve when participating in a weight-loss program.5 While VBBD may not be the ideal benefit structure for all employers, it is an innovative solution that may prove beneficial in terms of long-term health outcomes as well as decreased spending.
Table 1. FDA-Approved Antiobesity Pharmacotherapies15 Drug
Sympathomimetic amine that functions as a centrally acting appetite suppressant through pro-opiomelanocortin (POMC) neuronal activation
Short-term adjunct in a weight-loss regimen based on exercise, behavioral modification, and caloric restriction in the management of exogenous obesity for patients with an initial BMI ≥30 kg/m2 or ≥27kg/m2 in the presence of other risk factors
Inhibits absorption of dietary fat, both by inactivating lipase enzymes and inhibiting triglyceride hydrolysis in the gut
Adjunct to reduced-calorie diet in obesity management, including weight loss and weight maintenance in patients with initial BMI ≥30 kg/m2 or ≥27kg/m2
Serotonin 2C receptor agonist that acts to suppress appetite via activation of hypothalamic POMC neurons, which play a key role in appetite regulation and energy expenditure
Adjunct to reduced-calorie diet and increased physical activity for chronic weight management in adults with initial BMI ≥30 kg/m2 or ≥27kg/m2 in the presence of at least one weightrelated comorbidity
Phentermine is an appetite suppressant and stimulant; topiramate is an anticonvulsant used as an antiepileptic with a weight-loss side effect
Adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial BMI of ≥30 kg/m2 or ≥27kg/m2 in the presence of at least one weight-related comorbidity
Naltrexone is an opioid antagonist; bupropion is an antidepressant of the aminoketone class that inhibits neuronal reuptake of dopamine and norepinephrine
Adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial BMI of ≥30 kg/m2 or ≥27kg/m2 in the presence of at least one weight-related comorbidity
GLP-1 receptor agonist that acts on the GLP-1 receptor in the hypothalamus to reduce hunger and increase satiety
Adjunct to reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial BMI of ≥30 kg/m2 or ≥27kg/m2 in the presence of at least one weightrelated comorbidity
Multifaceted Approach In order to achieve long-term success, weight-loss programs should make various treatments and management strategies such as weight maintenance, behavioral therapy, pharmacotherapy options, physical fitness initiatives, and surgical options available when clinically appropriate.7, 8 Limiting the availability of any proven-effective weight-loss strategies would reduce the likelihood of success. An OptumHealth survey of 505 public and private employers reported that employees are willing to pay higher premiums for workplace wellness programs, creating potential for employers to offset costs.9 Employers that offer employees robust wellness programs often report positive return on investment, reflected in healthier employees, less absenteeism, increased productivity, lower premiums per employee, and decreased overall healthcare costs.9 The key to an effective weight-management program is to expand resources and initiatives beyond bariatric surgery and address the varying factors contributing to overweight and obesity. Additionally, programs must encourage employee engagement with key interventions.
Behavioral Health Component Managing overweight and obesity requires a targeted intervention strategy, often including a psychological component; researchers
note that long-term and constant behavioral vigilance will lead to the most successful weight-loss maintenance.10 Within a successful weight-loss program, behavioral therapy can help participants develop long-term skills, such as healthy eating and physical activity habits, to lose weight and maintain weight loss.11 It can take a variety of forms, including in-person counseling, group sessions, or interactive technology-based interventions. Smartphones are a convenient modality for behavioral weight-loss therapy, as they provide access to resources at the users’ fingertips.11 In a clinical trial of a smartphone technology enhancing self-monitoring and feedback within a weight-loss program, results showed remarkable achieved weight loss and adherence, as well as retention, when compared to behavioral therapy provided in group and individual in-person sessions.5 Smartphone-based behavioral interventions provide a sense of privacy and remove the vulnerability that could prevent many potential candidates from participating in this aspect of a weight-loss program. Studies show that weight-loss programs with a focus on behavioral health can provide significant outcomes and potential cost savings with reasonable implementation costs.12 Additionally, some evidence suggests that the cost-effectiveness of behavioral weight-loss therapy increases over the long term, over a period of 10 years.13
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MANAGING OBESITY | Continued
The U.S. Food and Drug Administration (FDA) has approved several weight-loss drugs as part of a comprehensive program targeting obesity that includes diet and exercise (see Table 1). Antiobesity medications may be an appropriate solution for obesity management, especially for patients with obesity-related complications such as cardiovascular disease and diabetes; in these cases, pairing behavioral health therapy with a targeted weight-loss drug could be effective.5 Studies show that when combined with lifestyle intervention, FDA-approved medications for long-term obesity treatment can lead to greater weight loss than lifestyle intervention alone.14 Given the proven effectiveness of pharmacotherapies in a comprehensive treatment strategy, an effective weight-management program would likely include access for qualifying patients to appropriate weight-loss drugs.
A comprehensive weight-management program providing access to varying treatment strategies can improve health outcomes for employees and economic outcomes for employers. A thoughtful approach requires employers to apply learnings regarding advances in obesity management, work within their organization, and partner with medical benefit insurers. Through these collective efforts, employers will be equipped to structure an appropriate benefit design with their health plan — coordinating medical benefits, pharmacy benefits, and employer-sponsored initiatives — and ensure that employees are able to utilize effective therapies that will help them achieve weight-loss goals and maintain long-term success.
“From Evidence to Practice: Workplace Wellness that Works.” Institute for Health and Productivity Studies, Johns Hopkins Bloomberg School of Public Health. Transamerica Center for Health Studies, September 2015, https://www.transamericacenterforhealthstudies. org/docs/default-source/wellness-page/from-evidence-to-practice--workplace-wellness-that-works.pdf?sfvrsn=2. Pickering, Laurel et al. “Weight Control and the Workplace: Employers and Health Plans Explore Their Toughest Health Improvement Challenge.” Northeast Business Group on Health. Oct. 31, 2013, http://nebgh.org/wp-content/uploads/2016/04/NEBGH_SC_ WeightControlFINAL10-31-13.pdf. Pollitz, Karen and Matthew Rae. “Workplace Wellness Programs Characteristics and Requirements.” Kaiser Family Foundation, May 19, 2016, http://www.kff.org/private-insurance/issue-brief/workplacewellness-programs-characteristics-and-requirements/.
“Value-Based Insurance Design.” National Conference of State Legislatures, Dec. 10, 2016, http://www.ncsl.org/research/health/ value-based-insurance-design.aspx.
Nobel, Jeremy et al. “Weight Control and Employees: One Size Doesn’t Fit All: Practical Guidance for Implementing Weight Control Programs in the Workplace.” Solutions Center. Northeast Business Group on Health, October 2014, http://nebgh.org/wp-content/ uploads/2015/02/Weight_Control-2014-FINAL.pdf.
Miller, Stephen. “Value-Based Insurance Design Sparks Increased Interest.” Society for Human Resource Management, Feb. 11, 2009, https://www.shrm.org/resourcesandtools/hr-topics/benefits/pages/ value-basedinsurancedesignsparksincreasedinterest.aspx.
Acharya, Sushama D. et al. “Adherence to a behavioral weight loss treatment program enhances weight loss and improvements in biomarkers.” Patient Preference and Adherence, June 12, 2009, https://doi.org/10.2147/ppa.s5802.
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Karasu, Sylvia R. “Psychotherapy-Lite: Obesity and the Role of the Mental Health Practitioner.” The American Journal of Psychotherapy, April 30, 2018, https://doi.org/10.1176/appi. psychotherapy.2013.67.1.3.
Trogdon, J.G. et al. “Indirect costs of obesity: A review of the current literature.” Obesity Reviews, Aug. 11, 2008, https://doi. org/10.1111/j.1467-789X.2008.00472.x.
10. Odom, Jacqueline et al. “Behavioral Predictors of Weight Regain after Bariatric Surgery.” Obesity Surgery, June 25, 2009, https://doi. org/10.1007/s11695-009-9895-6. 11. Thomas, J. Graham and Rena R. Wing. “Health-E-Call, a SmartphoneAssisted Behavioral Obesity Treatment: Pilot Study.” JMIR mHealth and uHealth, April 17, 2013, https://doi.org/10.2196/mhealth.2164. 12. Stumbo, Scott P. et al. “Costs of implementing a behavioral weightloss and lifestyle-change program for individuals with serious mental illnesses in community settings.” Translational Behavioral Medicine, May 30, 2015, https://doi.org/10.1007/s13142-0150322-3. 13. Tsai, A.G. et al. “Cost-effectiveness of a primary care intervention to treat obesity.” International Journal of Obesity, Aug. 6, 2013, https://doi.org/10.1038/ijo.2013.94. 14. Yanovski, Susan Z. and Jack A. “Long-term Drug Treatment for Obesity: A Systematic and Clinical Review.” The American Journal of Medicine, Jan. 1, 2014, https://doi.org/10.1001/jama.2013.281361. 15. Daneschvar, H.L. et al. “FDA-Approved Anti-Obesity Drugs in the United States.” The American Journal of Medicine, March 3, 2016, https://doi.org/10.1016/j.amjmed.2016.02.009.
PI PE LI N E D RU G LIST
PIPELINE DRUG LIST
Expected FDA Approval
MDD (with suicidal ideation with intent)
sNDA; breakthrough therapy; fast-track
Peanut allergy (in ages 4 to 11 years)
BLA; breakthrough therapy; fast-track
NSCLC (first-line, metastatic or recurrent, EGFR- and ALK-negative, in combination with nivolumab)
sBLA; fast-track; priority review
NSCLC (first-line, metastatic or recurrent, EGFR- and ALK-negative, in combination with ipilimumab and chemotherapy)
sBLA; fast-track; priority review
PSO (in ages 6 to 11 years)
Mantle cell lymphoma (relapsed/refractory)
BLA; breakthrough therapy; orphan drug; priority review
Chemotherapy-induced ototoxicity prevention
NDA; breakthrough therapy; fast-track; orphan drug
GIST (prior treatment with imatinib, sunitinib, and regorafenib)
NDA; breakthrough therapy; orphan drug; priority review; RTOR
Multiple myeloma (relapsed/refractory)
BLA; breakthrough therapy; orphan drug; priority review
NMO (Devic’s disease)
BLA; breakthrough therapy; orphan drug
HIV-1 (switch therapy)
Abbreviations: AML = acute myelogenous leukemia; BLA = biologics license application; CKD = chronic kidney disease; CLL = chronic lymphocytic leukemia; DLBCL = diffuse large B-cell lymphoma; DMD = Duchenne muscular dystrophy; GIST = gastrointestinal stromal tumor; GvHD = graft-versus-host-disease; HRS = hepatorenal syndrome; IBS = irritable bowel syndrome; IM = intramuscular; IN = intranasal; IV = intravenous; MDD = major depressive disorder; NDA = new drug application; NMO = neuromyelitis optica; NSCLC = non-small cell lung cancer; OTDD = oral transmucosal drug delivery; PO = oral; PSO = psoriasis; RA = rheumatoid arthritis; RTOR = real-time oncology review; sBLA = supplemental biologics license application; SC = subcutaneous; SCLC = small cell lung cancer; SLL = small lymphocytic lymphoma; SMA = spinal muscular atrophy; sNDA = supplemental new drug application; TD = transdermal
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PI PE LI N E D RU G LIST
PIPELINE DRUG LIST CONT.
Expected FDA Approval
NDA; accelerated approval; orphan drug; priority review
NDA; priority review
Breast cancer (HER2+ in combination with chemotherapy)
BLA; breakthrough therapy; orphan drug; priority review
CKD-related metabolic acidosis
SMA (types 1, 2, 3)
Breakthrough therapy; fasttrack; orphan drug; priority review
DLBCL (relapsed/ refractory, postlenalidomide monotherapy)
BLA; breakthrough therapy; fast-track; orphan drug; priority review
testosterone undecanoate (TLANDO™)
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Y & TRADITIONAL DRUGS A VIEW INTO UPCOMING SPECIALT
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52 | Magellan Rx Report | Summer 2020
PI PE LI N E D RU G LIST
PIPELINE DRUG LIST CONT.
Expected FDA Approval
ibrutinib (Imbruvica )
CLL/SLL (first-line, in ages <70 years, in combination with rituximab)
sNDA; orphan drug; RTOR
Type 1 HRS
Fast-track; orphan drug
Growth hormone deficiency (in adults)
diazepam buccal film (Libervant™)
505(b)(2); fast-track; orphan drug
GvHD (steroid-refractory, pediatric)
BLA; fast -rack; orphan drug; priority review
HIV vaccine (Remune)
Immune Response BioPharma
BLA; orphan drug
hydrocortisone granules (Alkindi®/ Infacort®)
Adrenal insufficiency (ages <17 years)
505(b)(2); orphan drug
Pain (moderate to severe, medically supervised setting)
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