PerformRx Review - Summer 2023

Optimizing Therapeutic Outcomes for Your Members

PerformRx’s URAC-accredited Drug Therapy Management (DTM) Program encompasses multiple holistic disease management programs, a CMS-compliant Part D Medication Therapy Management (MTM) program, and quality measure improvement programs. Managed by a team of clinical pharmacists (many of whom are boardcertified), registered nurses, and certified pharmacy technicians, our DTM programs can be tailored to meet the specific needs of your population. PerformRx’s proprietary applications afford us the specialized dexterity to design, implement, and manage your entire DTM program.

Jim Gartner, MBA, RPh President PerformRx and PerformSpecialty

A Message From the President of PerformRx

Dear PerformRx Review readers:

Welcome to the Summer 2023 issue of PerformRx Review. In this edition, we are excited to present a collection of insightful articles that shed light on the latest advancements in the field. As the pace of innovation in health care accelerates, it is crucial to share the impactful progress being made.

At PerformRx, we firmly believe in the power of robust pharmaceutical care management programs that harness the expertise of both clinical and retail pharmacists. By utilizing this collaborative approach, we can achieve better outcomes for the members we serve while exploring new strategies and breakthroughs that pave the way forward.

One area of focus in this issue is the advancement of Respiratory Syncytial Virus (RSV) treatment. We delve into RSV's background in the U.S., current treatment options, and the exciting therapies under development for infants and adults. With a clear public health need for additional preventative options, we anticipate the potential approval of three new products at the start of the next RSV season, which could revolutionize longterm treatment approaches.

Furthermore, we delve into the emergence of digital therapeutics and its potential to enhance access to personalized care. While still in its early stages, digital therapeutics holds promise in improving patient outcomes, reducing the overall cost of care, and advancing health equity. We examine current use cases and explore the opportunities this digital transformation presents.

In this issue, we also highlight PerformRx's Clinical Outcomes and Therapeutics (COTO) team's approach to comprehensive medical reviews. With a significant percentage of Americans taking multiple medications, there is an inherent risk. By dedicating time to individual patient care, PerformRx aims to drive improvements across the population and ensure the safety and efficacy of medication regimens.

Additionally, we discuss the vital role and shared responsibility of pharmacists in advancing asthma management. At PerformRx, our Asthma Management DTM Program, in collaboration with various health plan partners, provides a unique opportunity to drive improved outcomes and enhance the quality of care for asthma patients.

As passionate industry professionals committed to delivering quality and affordable care, we must constantly explore new techniques and refine strategies to achieve the best possible outcomes for our members. Our goal is to offer thought-provoking viewpoints that spark discussion and intuition among our readers, bringing us closer to our shared mission.

We invite you to immerse yourself in this edition of PerformRx Review, and we hope that these articles will inspire meaningful conversations and drive us further towards our common goal of delivering exceptional care to all.

Best regards,

Jim Gartner, MBA, R.Ph. President PerformRx & PerformSpecialty #BetterTogether

What Are Digital Therapeutics?

EDITORIAL STAFF

John Butts

Travis Taylor

MEDIA RELATIONS CONTACT

Scott D. Bluebond

1-215-840-8605 mediarelations@performrx.com

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John C. Butts

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DISCLAIMER

The contents of PerformRx Review are copyrighted by PerformRx. The contents are presented for informational and educational purposes only, and should not be construed as medical advice. Never delay or disregard professional medical advice because of something you have read in this publication. The inclusion of third-party advertisements does not constitute an endorsement, recommendation, guarantee, or warranty by PerformRx of any product or service. Any advertiser appearing in this publication has no influence on content or presentation. PerformRx Review is provided to its readers at no charge.

ABOUT PERFORMRX

PerformRx is a pharmacy benefit manager (PBM) dedicated to clinical culture, boutique service, and holistic solutions. Our mission is to help customers, doctors, and patients use effective medication therapy to improve health and wellness. For more than 20 years, our focus has been on providing optimal service through a clinical culture that seeks to provide members with high-quality care while ensuring our partners receive favorable costs.

ABOUT PERFORMSPECIALTY

PerformSpecialty is a full-service specialty pharmacy. Our goal is to provide personalized patient care and better access to achieve healthier outcomes. Each patient works with a Patient Care Coordinator, who along with the prescriber creates a program to treat each condition individually and works to involve the patient in their own health.

PerformRx www.performrx.com

1-866-533-5492

ABOUT AMERIHEALTH CARITAS

PerformSpecialty www.performspecialty.com

1-855-287-7888

AmeriHealth Caritas is one of the nation’s leaders in health care solutions for those most in need. Operating in 13 states and the District of Columbia, AmeriHealth Caritas serves approximately 5 million Medicaid, Medicare, Children’s Health Insurance Program (CHIP), and Health Insurance Marketplace® members through its integrated managed care products, pharmaceutical benefit management and specialty pharmacy services, and behavioral health services. Headquartered in Newtown Square, PA., AmeriHealth Caritas is a mission-driven organization with more than 40 years of experience serving low-income and chronically ill populations.

For more information, visit www.amerihealthcaritas.com.

VALUE-ADDED SERVICE: Asthma Management

Courtney McMahon, PharmD, BCACP

Asthma is a serious but treatable health condition characterized by chronic inflammation of the airways. Most common asthma symptoms include respiratory manifestations such as wheezing, coughing, and shortness of breath.1 Although asthma is most prevalent in children and adolescents, the impact of the disease spans across all stages of life and can change over time.2 In fact, children younger than five years old have the highest asthma attack rates, but asthma death rates are greatest among individuals older than 65 years old.2,3 Overall more than 350 million people across the world are affected by asthma and its prevalence continues to climb in many countries.1,3 In addition to health-related impacts, asthma imposes significant financial burdens as well. Uncontrolled asthma is associated with loss of productivity at work or school and an undue financial and resource burden at the individual and population level.1 The American Lung Association reported that asthma, in the United States alone, accounted for $81.9 billion annually in economic costs, including direct health care costs, mortality, and missed school and workdays, from 2008 to 2013.2

Despite ongoing, concerted efforts surrounding appropriate asthma management, recent studies indicate that asthma control is still suboptimal in many areas, especially within the pediatric population and nations with low incomes. The U.S. is often thought of as a highincome country, however, there are still significant populations in the U.S. whose clinical outcomes are limited by the availability, accessibility, and affordability of appropriate asthma medications.2 In conjunction with lack of medication and health care access, lack of evidence-based treatment acceptance and use also significantly impacts asthma outcomes.1,2

The 2022 GINA Report, Global Strategy for Asthma Management and Prevention outlines clinical recommendations and best practices for the management of asthma. This guideline highlights the need for increased access to effective medications and the implementation of asthma management recommendations in practice to drive improved asthma care and optimal patient outcomes. It is also noted that putting evidence-based guidelines into practice requires a concentrated multidisciplinary effort and consideration of social determinants of health (SDOH).1

The pharmacist’s role

The pharmacist is a key member of the patient’s health care team that shares responsibility for advancing asthma management. In addition to reviewing medication regimens and making clinical interventions, a pharmacist, as the medication expert, also has the training and accessibility to help overcome several provider and patient barriers limiting implementation and uptake of evidence-based recommendations in the real world.

A pharmacist can assist a provider with updates to evidence-based clinical recommendations, application of guideline to clinical practice and time and resource constraints. Patient barriers impacting appropriate asthma care include low health literacy, cultural and economic barriers, and inadequate understanding of the disease state and treatment options. During a comprehensive medication review, a pharmacist has the time and knowledge to educate members, explain treatment options, and address any questions or concerns from a patient with the goal of empowering

Asthma, in the United States alone, accounted for $81.9 billion annually in economic costs, including direct health care costs, mortality, and missed school and workdays, from 2008 to 2013.2

them to manage their asthma and overall health.

In addition, the clinical pharmacy team at the patient’s pharmacy benefit manager (PBM) has a unique and advantageous perspective of a patient’s overall care and the ability to drive improved outcomes. Ideally, a PBM has insight into pharmacy and medical claims, and medication formulary status — all of which are important when assessing disease state management and making recommendations. As a PBM committed to advancing the quality of care provided to patients and improving overall health outcomes, PerformRx has designed and implemented asthma drug therapy management (DTM) programs in collaboration with several health plan partners to help drive improvement in asthma care and patient outcomes.

The asthma DTM program enrollment criteria are flexible and can be adjusted to meet the needs of a specific client or population, but typically targets asthmatic patients found to be non-adherent to controller medication or over-utilizing rescue inhalers, and patients with recent asthma-related emergency room visits and hospitalizations.

The goals of the PerformRx asthma DTM program include:

• Optimize medication regimens as evidenced by fewer gaps in evidence-based care, fewer safety issues such as drug interactions and duplicate therapies, improved controller medication adherence, and improved Healthcare Effectiveness Data and Information Set (HEDIS) quality scores.

• Improve patient outcomes in surrogate markers of health (such as lung function test results), decreased utilization of emergency health services, and increased quality of life.

• Decrease the cost of care (pharmacy cost increases because of closed care gaps and improved medication adherence are expected to be more than offset by medical cost savings).

Due to the complexity of asthma management and the number of external factors that impact asthma outcomes, each member enrolled in the DTM program is offered a holistic comprehensive medication review with a pharmacist. The pharmacist reviews the member profile, which includes demographic information and pharmacy and medical claims, in addition to any information gathered from the patient consultation.

Medication-related problems are identified, prioritized, and addressed based on the clinical review. The pharmacist will address each intervention with the patient or the prescriber, or both. An individual issue may be addressed with one or more providers to facilitate collaboration among the patient’s health care team.

An important piece of the PerformRx DTM program is collaboration with our health plan partners. This partnership includes a two-way referral process that expands the resources available to patients as they are offered both DTM and case management services when needed. This program design creates a pathway for quick and effective resolution of SDOH-related issues. SDOH significantly impact a patient’s health and contribute to health disparities. A collaborative approach to addressing these drives health equity improvements.4

Program impact and outcomes

Follow-up on each individual patient and provider intervention is completed, and pharmacy and medical claims are used to determine an outcome. The acceptance of interventions is tracked and reported quarterly to the health plan. Traditionally, the provider acceptance rate for the PerformRx DTM program provider recommendations is 41%. On a larger scale, a cost and utilization analysis was completed for the asthma DTM program in one Medicaid line of business in 2022. The enrollment time period included in the evaluation was January 1, 2019, to June 30, 2021. The analysis concluded that medical utilization and cost decreased after program enrollment and intervention.

OUR AUTHORS

REFERENCES

1. Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma, 2022. Available from: www.ginasthma.org

2. Asthma trends and burden. American Lung Association, 2018. Available from: https:// www.lung.org/research/trends-in-lung-disease/asthma-trends-brief/trends-and-burden

3. Garcia-Marcos L et al., Asthma management and control in children, adolescents, and adults in 25 countries: a Global Asthma Network Phase I cross-sectional study. Lancet Glob Health 2023;11:e218-228.

4. “Healthy People 2030,” U.S. Department of Health and Human Services, Office of Disease Prevention and Health Promotion. Retrieved September 2, 2022, from https://health.gov/ healthypeople/objectives-and-data/social-determinants-health

The program design creates a pathway for quick and effective resolution of SDOH-related issues.

Courtney McMahon PharmD., BCACP PerformRx

A New Chapter in Respiratory Syncytial Virus (RSV) Management

Jonathan Doles, PharmD, CSP, Hansel Fernandes, PharmD,

Respiratory syncytial virus (RSV) is a single-stranded, negative-sense ribonucleic acid (RNA) respiratory virus that infects the lungs and airways.1 RSV affects patients of all ages and causes upper respiratory cold-like symptoms, such as runny nose, cough, sneezing, and fever.2 However, some patients, especially the elderly and infants, are at risk for developing more serious illness. RSV can also lead to exacerbations of serious underlying conditions such as asthma, chronic obstructive pulmonary disease (COPD), and congestive heart failure. Because clinical symptoms of RSV are nonspecific and overlap with other respiratory infections, there are several types of laboratory tests to confirm an RSV infection. These include real-time reverse transcriptase-polymerase chain reaction (rRTPCR), antigen testing, viral cultures, and serology.3,4

Megan Henry, PharmD, and Shavonda Leakes, PharmD, CPh, CSP

Annually in the United States, RSV leads to approximately 2.1 million outpatient visits and 58,000 hospitalizations among children younger than five years of age.2 RSV is the most common cause of lower respiratory tract infections (LRTIs) in children younger than one year.3 Acute bronchiolitis due to RSV is the leading cause of U.S. infant hospitalizations.⁵ In the global population, RSV is estimated to cause 2.3% of deaths among neonates 0 to 27 days old, 6.7% of deaths among infants 28 to 364 days old, and 1.6% of deaths among children 1 through 4 years old.6 In adults 65 years and older, RSV leads to approximately 177,000 hospitalizations and 14,000 deaths per year.1 The mortality rate among hospitalized adults 50 years and older is 6 to 8%.7 Annually in the United States, the treatment cost of RSV in infants is $709.6 million.5 In patients 60 years and older, RSV-related direct health care costs are estimated to be $3.2 billion for hospitalized patients, $690 million for outpatient care, and $23 million for ill, nonmedically attended patients per year.8

Among infants and children, high risk patients include premature infants, infants younger than six months, children younger than two years with chronic lung disease or congenital heart disease, immunosuppressed children, and children with neuromuscular disorders.1 Among adults infected with RSV, symptoms are usually consistent with an upper respiratory infection and the virus lasts less than five days. Some adults may have more severe symptoms consistent with a LRTI, such as pneumonia. Adults older than 65 years, those with chronic heart or lung disease, and the immunocompromised are at risk for more severe illness.1

RSV causes seasonal outbreaks throughout the world. In the U.S., RSV primarily occurs during the fall, winter, and spring, but the timing and severity of RSV season can vary from year to year. Disruption of the typical seasonal pattern, such as during the COVID-19 pandemic, may result in off-season outbreaks.1,3,4

Current treatment

Mild RSV infections will typically resolve in one to two weeks with supportive care, such as rest and hydration. Over-the-counter fever reducers (such as acetaminophen) and pain relievers (such as ibuprofen and naproxen) can help manage symptoms.4 Patients that require hospitalization may need oxygen, intubation, and mechanical ventilation.1 There are no FDA-approved agents for the treatment of RSV. Until recently, Synagis® (palivizumab), a recombinant humanized monoclonal antibody, had been the only FDA-approved agent for the prevention of RSV.9 The recommended dose of Synagis® is weight based and given once a month throughout the RSV season (typically five doses) and costs approximately $5,000 to $10,000 per treatment course.2 Synagis® is not recommended or FDAapproved for RSV prevention in adults.9

Synagis® has a specific use and is indicated for the prevention of serious lower respiratory tract disease caused by RSV in pediatric patients:

• With a history of premature birth (≤ 35 weeks gestational age) and who are six months of age or younger at the beginning of RSV season

• With bronchopulmonary dysplasia (BPD) that required medical treatment within the previous six months and who are 24 months of age or younger at the beginning of RSV season

• With hemodynamically significant congenital heart disease (CHD) and who are 24 months of age or younger at the beginning of RSV season

RSV can also lead to exacerbations of serious underlying conditions such as asthma, chronic obstructive pulmonary disease (COPD), and congestive heart failure.

RSV activity usually begins in the late fall and extends through spring. During the COVID-19 pandemic, measures such as mask wearing and social distancing were associated with reductions in non-COVID-19 respiratory infections in children, including RSV, during the winter season. Now that those measures have been relaxed, however, an increase in interseasonal RSV activity in the spring and summer has been observed in some regions. The American Academy of Pediatrics (AAP) makes recommendations for the use of palivizumab, and their recommendations have changed with the varying RSV season. For the 2022 - 2023 season, the AAP issued updated guidance for the use of palivizumab prophylaxis to prevent hospitalization from severe RSV infection. The AAP supports continued palivizumab use (more than the typical five doses) in regions where RSV activity remains high.10,11

Pipeline/New agents

Two vaccines, as well as a monoclonal antibody, are in late-stage development or have recently been FDAapproved for RSV prevention. The two vaccines are GlaxoSmithKline’s (GSK) Arexvy® and Pfizer’s Abrysvo®. The monoclonal antibody is AstraZeneca/Sanofi’s nirsevimab. One of the major differences between the vaccines is that Arexvy® is only being studied for the adult population, while Abrysvo® is being evaluated for adults and pediatrics. For the pediatric indication, some literature refers to Abrysvo® as RSVpreF.2

The two vaccines would help fill the unmet need for RSV prevention in the adult population. Both are one-dose vaccines given in preparation for RSV season. Arexvy® was approved on May 3, 2023, and is the first RSV vaccine approved for the older adult population.12 Abrysvo® was also approved for the same population shortly after on May 31, 2023. The FDA has also granted priority review to Abrysvo® for use in healthy individuals in late pregnancy to help protect infants from RSV disease after birth, with a decision expected by August 2023.2,13,14

AstraZeneca/Sanofi’s monoclonal antibody, nirsevimab, is being evaluated for the prevention of RSV infections in healthy and high-risk infants. If approved, nirsevimab may compete with Pfizer’s RSV vaccine for the infant protection. Additionally, it would compete with Synagis® for the indication of infants and young children at high risk

of serious RSV. The FDA accepted the Biologics License Application (BLA) in January 2023, and approval is possible in third quarter of 2023.2, 15,16

Arexvy® Abrysvo®/ RSVpreF Nirsevimab

Manufacturer GSK Pfizer AstraZeneca/ Sanofi

Population Older adults Older adults and infants Infants

Mechanism of action Viral vaccine Viral vaccine Monoclonal antibody

Table 1: Pipeline Agents Overview

Agents

Arexvy®

CLINICAL SUMMARY

GSK’s vaccine, Arexvy®, contains a recombinant subunit prefusion RSV F glycoprotein antigen combined with GSK’s proprietary AS01E adjuvant.17 On March 1, 2023, the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted in favor of approval unanimously 12-0 on effectiveness and 10-2 on safety.2 Arexvy® was formally approved on May 3, 2023, for the prevention of LRTI in adults 60 years of age and older. GSK has yet to disclose a specific price, but company executives have indicated it will cost between $60 to $185.12 The exact final price will not be known until the vaccine formally hits the market.

CLINICAL TRIALS

Abrysvo®/ RSVpreF (for pediatric use) CLINICAL SUMMARY

Pfizer is pursuing approval for a bivalent vaccine candidate that would offer RSV protection for both older adults and infants. If approved, RSVpreF will be administered to healthy individuals in late pregnancy to help protect infants from RSV disease after birth. Unlike Arexvy®, Abrysvo® does not contain an adjuvant, which may improve tolerability. The FDA VRBPAC voted in favor of approval 7-4 on effectiveness and 7-4 on safety of Abrysvo®.2,19 Some advisory committee members had more hesitations about Abrysvo® than Arexvy® due to not enough patients in Pfizer’s trial being infected with RSV to assess the vaccine’s efficacy. Additionally, advisers expressed concern about the potential for Abrysvo’s® association with Guillain-Barre syndrome. The FDA asked Pfizer to perform a post-marketing study to further evaluate the risk.2,20 Abrysvo® was formally approved on May 31, 2023, for the prevention of LRTI in adults 60 years of age and older. The indication for infants is expected by August 2023. This vaccine is likely to be priced similarly to Arexvy®.2 The exact final cost will not be known until the vaccine formally hits the market.

CLINICAL TRIALS

2,17,18

The phase 3 trial evaluating Arexvy®, AReSVi 006, enrolled 25,000 adults 60 years of age and older. Results indicate that the vaccine met the primary endpoint and reduced cases of LRTI by 82.6% when compared to a placebo. The efficacy results were higher among more severely ill patients with two or more lower respiratory signs/symptoms, with a 94.1% reduction. The vaccine protection was considered statistically significant in all patient groups except two. In patients 80 years and older, only two participants receiving the vaccine and three given a placebo acquired RSV, which was not statistically significant. Likewise, the difference was not statistically different among participants considered frail. The trial is ongoing and will continue to analyze the annual revaccination schedule and long-term protection over multiple seasons after a single dose of the vaccine.

Abrysvo® has phase 3 data in pregnant women and older adults.21 The phase 3 RENOIR trial enrolled 30,000 adults age 60 and older. An interim analysis found the Abrysvo® vaccine offered 66.7% efficacy in protection against RSVassociated lower respiratory tract illness (defined by two or more symptoms). Efficacy in protection against three or more symptoms was 85.7%.2,21 The phase 3 MATISSE trial enrolled 7,400 patients and evaluated the vaccine versus placebo in pregnant patients. The study investigated the RSVpreF vaccine for the prevention of medically attended lower respiratory tract illness (MA-LRTI) and severe MA-LRTI caused by RSV in infants from birth up to 6 months of age by active immunization of pregnant individuals. RSVpreF was shown to be 81.8% effective in preventing severe MA-LRTI through the first 90 days of life, however, it dropped to 69.4% efficacy at the sixmonth mark.2

Nirsevimab

CLINICAL SUMMARY

AstraZeneca/Sanofi’s nirsevimab is a single-dose fusion antibody with an extended half-life. Nirsevimab is being evaluated in two phase 3 clinical trials, MELODY and MEDLEY. Nirsevimab is being developed as a preventive RSV option for the broad infant population, including healthy term or preterm infants. Unlike Synagis®, which is administered on a monthly dose schedule, nirsevimab has the advantage of a single-dose administration due to its extended half-life.2,15,16 The manufacturers are also pursuing an indication for RSV prevention during the second RSV season for infants at high risk based on data from the MEDLEY trial. Nirsevimab is expected to cost less than $5,000 for a single dose.2 As with the other pipeline agents, the final cost for nirsevimab will not be known until the product is approved and hits the market.

CLINICAL TRIALS

Results from three trials demonstrated that nirsevimab protects infants during their first RSV season against RSV infection with a single dose. In the Phase 2b randomized, placebo-controlled study, nirsevimab showed a significant reduction in medically attended LRTI and hospitalizations caused by RSV in healthy preterm infants compared to placebo. Data from the phase 2b study was used to recommend dosing for the subsequent phase 3 trial, MELODY.2,15,16

In the phase 3 randomized, placebo-controlled MELODY trial, nirsevimab met the primary endpoint with a statistically significant reduction in the incidence of medically attended LRTI compared to placebo in healthy late preterm babies (35 weeks gestational age or greater) entering their first RSV season. Medically attended RSV occurred in 1.2% of infants in the nirsevimab group, and 5% in the placebo group. These findings correspond to an efficacy of 74.5%. Hospitalization for RSV associated LRTIs occurred in six infants in the treatment group, and eight infants in the placebo group. It should be noted that COVID-19 limited the incidence of RSV infection during the trial, which investigators believe led to lower hospitalizations overall.2,15,16

In the phase 2/3, randomized, double-blind, Synagis®controlled MEDLEY trial, the safety and tolerability of nirsevimab was compared to Synagis® among 925 preterm and high-risk infants entering RSV season. Infants with

congenital heart disease (CHD) and/or chronic lung disease of prematurity (CLD) were included. Results showed nirsevimab has a similar safety profile to Synagis®. This safety profile was also consistent with the safety profile in term and preterm infants studied in the MELODY Phase 3 trial.2,15,16

Public health need

With Synagis® as the only RSV preventive option, there is a clear public health need for alternatives. Pending approval there could be three new products at the start of the next RSV season. Arexy®, Abrysvo®, and nirsevimab represent just a few of the many therapies that are in research and development for RSV. Moderna and Bavarian Nordic are also developing products that are currently in phase 3 trials.2 Because patients will respond differently to these preventive agents based on their age and immune status, researchers and physicians are hopeful with the variety of options that are in development and are eagerly awaiting the AAP update to see where these products fall in guidelines.13,14

REFERENCES

1. “Respiratory Syncytial Virus Infection (RSV) For Health Care Providers,” Centers for Disease Control and Prevention. Last updated October 28, 2022. https://www.cdc.gov/rsv/clinical/ index.html

2. “Infectious Diseases: Respiratory Syncytial Virus (RSV),” IPD Analytics, https://secure.ipdanalytics.com/User/Pharma/RxStrategy/Page/ df263e54-1655-4e2b-bd46-56a6c0886803#section-group-418884/

3. Frederick E Barr and Barney S Graham, “Respiratory syncytial virus infection: Clinical features and diagnosis,” UpToDate, Last updated April 22, 2022. https://www.uptodate. com/contents/respiratory-syncytial-virus-infection-clinical-features-and-diagnosis?search=rsv%20pathophysiology&source=search_result&selectedTitle=1~150&usage_ type=default&display_rank=1

4. Frederick E Barr and Barney S Graham, “Respiratory syncytial virus infection: Treatment,” UpToDate, Last updated April 22, 2022. https://www.uptodate. com/contents/respiratory-syncytial-virus-infection-treatment?search=rsv%20 treatment&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

5. Diana M Bowser et al., “Cost of Respiratory Syncytial Virus Infections in US Infants: Systematic Literature Review and Analysis,” J Infect Dis, Vol 226, 2022, pp 225-235.

6. Ting Shi et al., “Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study,” Lancet, Vol 390, 2017, pp 946-958.

7. Ann D Colosia et al., “The epidemiology of medically attended respiratory syncytial virus in older adults in the United States: A systematic review,” PLoS One, Vol 12, 2017.

8. Jessica K DeMartino et al., “Annual economic burden of respiratory syncytial virus infections among the 60+ population in the United States,” J Manag Care Spec Pharm, Vol 28, 2022, pp S1-S137.

9. Synagis® (palivizumab) prescribing information. Waltham, MA: Sobi, Inc. 2021

10. “Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection,” American Academy of Pediatrics Committee on Infectious Diseases; American Academy of Pediatrics Bronchiolitis Guidelines Committee, Pediatrics, Vol 134, 2014, pp 620-638.

11. “Updated guidance: use of palivizumab prophylaxis to prevent hospitalization from severe respiratory syncytial virus infection during the 2022-2023 RSV season,” American Academy of Pediatrics, November 17, 2022. https://www.aap. org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/ interim-guidance-for-use-of-palivizumab-prophylaxis-to-prevent-hospitalization/

12. Zoey Becker, “Beating its rivals, GSK nabs world-first approval for adult RSV vaccine Arexvy®,” Fierce Pharma, May 3, 2023, https://www.fiercepharma.com/pharma/ beating-rival-pfizer-gsk-nabs-world-first-approval-adult-rsv-vaccine-arexvy

13. Aria Bendix, “The race to an RSV vaccine is nearly over, decades after the first attempt” NBC News, February 16, 2023, https://www.nbcnews.com/health/health-news/ rsv-vaccine-candidates-timeline-fda-approval-rcna70777

14. Aria Bendix, “Paving the way for the world’s first RSV vaccine, FDA advisers recommend two different shots,” NBC News, February 28, 2023. https://www.nbcnews.com/health/ health-news/fda-advisers-recommend-first-rsv-vaccine-rcna72535

15. Laura L Hammitt et al., “Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants,” N Engl J Med, Vol 3, 2022, pp 837-846.

16. “Nirsevimab US regulatory submission accepted for the prevention of RSV lower respiratory tract disease in infants and children up to age 24 months,” AstraZeneca Press Release, January 5, 2023, https://www.astrazeneca.com/media-centre/press-releases/2023/nirsevimab-us-regulatory-submission-accepted-for-the-prevention-of-rsv-lower-respiratory-tract-disease-in-infants-and-children.html

17. “US FDA Advisory Committee votes to support effectiveness and safety of GSK’s respiratory syncytial virus older adult vaccine candidate,” GSK Press Release, March 1, 2023, https:// www.gsk.com/en-gb/media/press-releases/us-fda-advisory-committee-votes-to-supporteffectiveness-and-safety-of-gsk-s-rsv-older-adult-vaccine-candidate/

18. “FDA Review of Efficacy and Safety of Arexvy® Biologics Licensing Application,” FDA Vaccines and Related Biological Products Advisory Committee Meeting, March 1, 2023, https://www.fda.gov/media/165731/download

19. “Vaccines and Related Biological Products Advisory Committee Meeting” FDA, February 28, 2023, https://www.fda.gov/media/165623/download

20. “Pfizer Receives Positive FDA Advisory Committee Votes Supporting Potential Approval for Vaccine Candidate to Help Combat RSV in Older Adults,” Pfizer Press Release, February 28, 2023, https://www.pfizer.com/news/press-release/press-release-detail/ pfizer-receives-positive-fda-advisory-committee-votes

21. “Pfizer Announces Positive Top-Line Data of Phase 3 Global Maternal Immunization Trial for its Bivalent Respiratory Syncytial Virus (RSV) Vaccine Candidate”, November 1, 2022, https://www.pfizer.com/news/press-release/press-release-detail/ pfizer-announces-positive-top-line-data-phase-3-global

Jonathan Doles PharmD, CSP PerformSpecialty

Megan Henry PharmD PerformRx

Hansel Fernandes PharmD PerformRx

Shavonda Leakes PharmD, CPh, CSP PerformSpecialty

Specialty Drug Pipeline Report

Jennifer Schonhorst, Pharm.D.

The PerformRx Pipeline Report provides a summary of potentially high-impact new medications and new indications that may be approved by the Food and Drug Administration in the next six months. It includes medications relevant to pharmacy and medical benefits. It is not inclusive of all new medications and new indications. For example, medications used for surgical purposes, such as general anesthetics, would not appear in this report. Medications are grouped by disease category and sorted alphabetically within each category.

The information contained in this report is compiled from independent third-party sources (see Bibliography)

and is provided for informational purposes only. This information should not be solely relied upon for decisionmaking purposes. Prospective drug launch dates are estimates based on market information. PerformRx does not guarantee any dates and the actual release dates are subject to change without notice. PerformRx makes no endorsement, express or implied, of any product, service, or information, by its inclusion or exclusion from this document. For questions pertaining to this report, please contact Lauren Megargell, Director of Clinical Services, at lmegargell@performrx.com

DERMATOLOGY

ENDOCRINE

Lantidra (donislecel)

Ocaliva (Obeticholic Acid)

HEMATOLOGY

Jesduvroq (daprodustat)

Inc.

Pharmaceuticals, Inc.

Mellitus, Type I

Kline plc

Due to Chronic Renal Failure, DialysisIndependent

HEMATOLOGY continued

Ex-vivo gene therapy; potential first gene therapy approved for treatment of SCD.

Novel therapy. Targets mannan-binding lectinassociated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system.

Roctavian (valoctocogene roxaparvovec)

INFECTIOUS DISEASE

Evusheld (tixagevimab/ cilgavimab)

Being developed for people with limited treatment options. Novel mechanism antifungal therapy from the newly discovered orotomide class.

Single dose option and seeking indication for broader infant population vs solely preterm infants or those with high-risk conditions.

Would be the first fully approved therapy for COVID-19 treatment in non-hospitalized patients. Ronapreve (casirivimab/ imdevimab)

Would be the first approved therapy for COVID-19 post-exposure prophylaxis. No other products, including those Emergency Use Authorized, are indicated for post-exposure prophylaxis. METABOLIC

Two component therapy consisting of the rhGAA cipaglucosidase and particularly bis-phosphorylated mannose-6 phosphate (bis-M6P) glycans, to enhance cellular uptake; it is administered in combination with oral Zavesca (miglustat).

Delandistrogene moxeparvovec (SRP-9001)

Eplontersen Ionis Pharmaceuticals, Inc. Hereditary Transthyretin (hATTR) Amyloidosis with Polyneuropathy

Livmarli (maralixibat)

Pharmaceuticals, Inc.

Familial Intrahepatic Cholestasis

Gene therapy which delivers micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein.

METABOLIC continued

Palovarotene Ipsen SA Fibrodysplasia Ossificans Progressiva (FOP)

NEUROLOGY

Selective RARγ agonist for the prevention of heterotopic ossification (new bone formation) as a treatment option for individuals living with FOP.

PO

NDA Fast Track Orphan

Duchenne Muscular Dystrophy (DMD) 10/26/2023

Ischemic

Stroke IV

Disease

NurOwn BrainStorm Cell Therapeutics Inc. NDA

Avasopasem Manganese Galera Therapeutics, Inc.

Radiotherapyinduced severe oral mucositis in patients being treated for head and neck cancer (HNC)

Dasynoc (dasatinib) Xspray Pharma AB Chronic Myelogenous Leukemia (CML)

Eflornithine/ Sulindac Mallinckrodt plc Familial Adenomatous Polyposis (FAP)

IV IT

Fast Track Orphan Rare Disease 07/07/2023

IV NDA Breakthrough Fast Track

08/09/2023 First in class agent for treatment of severe oral mucositis. Reduces elevated levels of superoxide caused by radiation therapy by rapidly converting superoxide to hydrogen peroxide and oxygen.

PO NDA 505b2 On or before 06/30/2023

PO NDA Fast Track Orphan On or before 06/30/2023

Bioequivalent to Sprycel with 30% lower dose.

Combination of eflornithine and sulindac. Eflornithine inhibits ornithine decarboxylase, reducing polyamine synthesis and destabilizing DNA to reduce cell growth. Sulindac is an NSAID that inhibits COX and prostaglandin synthesis and reduces inflammation.

patients with relapsed or refractory disease. Fruquintinib Takeda Pharmaceutical Co. Ltd. Colorectal Cancer PO NDA Fast Track 11/30/2023 A highly selective and potent oral inhibitor of VEGFR-1, -2 and -3. Seeking indication for refractory metastatic colorectal cancer. Glofitamab Roche Holding AG Diffuse Large B-Cell Lymphoma (DLBCL) - NHL IV BLA Rare Disease 07/01/2023 Seeking indication for relapsed/refractory dis-

after

antibody.

engaging

lymphocytes harvested from a patient's metastatic melanoma tumors, expanded in vitro, and infused back into the patient to attack the tumors.

two or more lines of systemic therapy. 06/16/2023 Alternative therapeutic option. SUMMER 2023 PERFORMRX REVIEW 19

ONCOLOGY continued

Aphexda (motixafortide)

Hepzato (melphalan hydrochloride for Injection/ Hepatic Delivery System)

Ltd.

Nirogacestat SpringWorks Therapeutics Inc.

Quizartinib Daiichi Sankyo Co., Ltd.

Repotrectinib Bristol Myers Squibb

Marrow Transplant and Stem Cell

Acute Myeloid Leukemia (AML)

Cell Lung Cancer (NSCLC)

Talquetamab Johnson & Johnson Multiple Myeloma (relapsed/ refractory)

A highly selective inverse agonist of chemokine (C-X-C motif) receptor 4, used to mobilize stem cells for bone marrow transplant in multiple myeloma patients.

Regionalized approach; administered via hepatic artery and the venous effluent of the liver is collected and filtered using a percutaneously placed catheter and filtration system. Submitted for approval of unresectable hepatic-dominant metastatic ocular melanoma.

A potential first-in-class and first-in-disease agent for desmoid tumors.

Targets the kinase FLT3, which is mutated and constitutively activated in 25-40% of AML patients and associated with poor prognosis.

Targeting treatment of patients with ROS1positive locally advanced or metastatic NSCLC.

Bispecific T-cell engager. Targets novel GPRC5D which is expressed on some normal cells but overexpressed on myeloma cells, and separately targets CD3.

Alternative therapeutic option. Designed to minimize binding to FcγR on macrophages which is theorized to improve efficacy relative to products lacking this feature.

BLA — biologics license application; ID — intradermal; IM — intramuscular; IN — intranasal; INS — instillation; INV—intravesical; IO — intraocular; IT—intrathecal; IV — intravenous; NDA — new drug application;

QIDP — Qualified Infectious Disease Product; sBLA — Supplemental Biologics License Application; SC — subcutaneous; sNDA — supplemental new drug application; SPA — special protocol assessment; TD— transdermal; TOP — topical

Glossary

Breakthrough — a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).1

Fast Track — a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.1

Orphan — drugs for the prevention, diagnosis, or treatment of diseases or conditions affecting fewer than 200,000 persons in the United States, or drugs that will not be profitable within seven years following approval by the U.S. Food and Drug Administration (FDA).2

Qualified Infectious Disease Product (QIDP) — a designation granted by the FDA to an antibacterial or antifungal drug for human use intended to treat serious or life-threatening infections. Products granted QIDP designation may also be eligible for Fast Track and Priority Review designations, and approved QIDP products gain an additional five years of regulatory exclusivity for the use for which the QIDP designation was granted.3

Regenerative Medicine Advanced Therapy (RMAT) — A drug designation applicable to cell therapies, therapeutic tissue engineering products, human cell and tissue products, or any combination product using such therapies or products; intended to treat, modify, reverse or cure a serious, lifethreatening disease or condition; which has the potential to address unmet medical needs.3

Special Protocol Assessment (SPA) — a process in which sponsors may request to meet with FDA to reach agreement on the design and size of certain clinical trials, clinical studies, or animal trials to determine if they adequately address scientific and regulatory requirements.4

OUR AUTHORS

Jennifer Schonhorst Pharm.D. PerformRx

REFERENCES

1. “Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review,” U.S. Food and Drug Administration, February 23, 2018, https:// www.fda.gov/patients/learn-about-drug-and-device-approvals/ fast-track-breakthrough-therapy-accelerated-approval-priority-review

2. “Recommended Tips for Creating an Orphan Drug Designation Application,” U.S. Food and Drug Administration, 2018, https://www.fda.gov/media/111762/download

3. “Qualified Infectious Disease Product Designation Questions and Answers,” U.S. Food and Drug Administration, January 2018, https:// www.fda.gov/regulatory-information/search-fda-guidance-documents/ qualified-infectious-disease-product-designation-questions-and-answers

4. “Regenerative Medicine Advanced Therapy Designation,” U.S. Food and Drug Administration, May 17, 2019, https://www.fda. gov/vaccines-blood-biologics/cellular-gene-therapy-products/ regenerative-medicine-advanced-therapy-designation

5. “Special Protocol Assessment Guidance for Industry,” U.S. Food and Drug Administration, April 2018, https://www.fda.gov/regulatory-information/ search-fda-guidance-documents/special-protocol-assessment-guidance-industry

BIBLIOGRAPHY

Center for Drug Evaluation and Research, U.S. Food and Drug Administration, “Qualified Infectious Disease Product Designation Questions and Answers — Guidance for Industry,” January 2018, https://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/UCM594213.pdf

Informa Pharma Intelligence Inc., BioMedTracker, Informa PLC, https://www.biomedtracker.com

IPD Analytics, http://www.ipdanalytics.com

Manufacturer press releases and websites.

U.S. Food and Drug Administration, http://www.fda.gov

Improving Care One Patient at a Time

Alex Ekstrom, PharmD, and Erika Kaplan, PharmD

For many, medications are an important part of daily life, and the burden is even more significant for patients with multiple chronic conditions and polypharmacy. Approximately 22% of Americans take five or more medications, and with more medications comes potential for risk, including adverse drug events.1

Adverse drug events, or the problems that stem from the use of medications, cause approximately 1.9 million emergency department visits and 768,000 hospitalizations annually.2 It is estimated that nearly 40% of these events are potentially avoidable.3 Patients often receive medications from multiple health care providers and may also be taking over-the-counter medications or herbal supplements that can further add risk and complexity to these regimens. Health care professionals, such as pharmacists, conduct comprehensive medication reviews (CMRs) to help coordinate overall care and avoid or resolve potentially preventable issues.

A CMR is a systematic and interactive approach to evaluating a patient's medication regimen and their understanding thereof. It involves, among other things, a thorough assessment of the patient's medical history, current health status, health literacy, and medication use. Broadly, the purpose of a CMR is to identify medication-related problems (MRPs) that the patient may have and resolve them. The benefits of a CMR are numerous for patients struggling with complex regimens. CMRs can improve a variety of patient outcomes, such as decreasing adverse drug events, improving control of chronic conditions, health literacy, and adherence to medications.4,5,6,7

Pharmacists and other health care professionals can also use the CMR process to address social determinants of health that may be affecting a patient's health outcomes.8 For example, a patient may be unable to adhere to their

medication regimen due to transportation challenges or difficulty accessing health care. Accessibility of a pharmacist during these interactions can even help resolve issues that would at times be considered outside of the scope of a medication review, such as helping to obtain necessary durable medical equipment, ensuring access to adequate food or housing, or coordinating necessary provider appointments. In such cases, pharmacists can work with the patient to identify resources such as insurance plan case management, social workers, transportation services, or telehealth options that can help them manage their health conditions effectively.

At PerformRx, the Clinical Outcomes and Therapeutic Optimization team has developed criteria and programs in partnership with health plans to help better identify patients who may benefit from a CMR. The team focuses on individual patients with goals and outcomes tailored to the specific needs of the patient. Below is an actual case highlighting one of these patient interactions.

Patient Case

Background and discussion

A telephonic comprehensive medication review was completed with the caregiver of a 73-year-old female with a past medical history of atrial fibrillation, chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD) with stent placement, diabetes, and hypertension.

The patient’s caregiver reported uncontrolled hypertension, CHF, and COPD. The caregiver explained they have not been able to monitor the patient’s blood pressure or weight at home following the addition of a new blood pressure medication. They have also had issues obtaining a higher dose of furosemide from the pharmacy to

Adverse drug events...cause approximately 1.9 million emergency department visits and 768,000 hospitalizations annually.2

help with the patient’s increased swelling. The caregiver reported non-adherence to tiotropium bromide inhaler and vitamin D due to a processing issue at the pharmacy.

In addition, the patient had less symptom control with budesonide/formoterol inhaler as compared to mometasone/formoterol, which the patient was previously taking. The caregiver also requested assistance with obtaining a shower chair and seeing if the patient qualifies for a meal benefit. The patient’s atrial fibrillation, diabetes, and CAD were assessed during the call and determined to be controlled on current therapy.

Intervention

Following the discussion with the caregiver, the pharmacist made several interventions to help coordinate the care of the patient. First, the pharmacist contacted patient services to ensure the over-the-counter catalog was sent to the patient so a scale and blood pressure monitor could be ordered. Second, the pharmacist

These interactions take place with over 14,000 patients each year, with services and populations expanding yearly.

contacted the pharmacy to assist with processing the patient’s vitamin D prescription. Third, the pharmacist contacted the prescriber to recommend a new prescription for furosemide and tiotropium bromide inhaler, notify them of non-adherence to therapy with tiotropium bromide inhaler, and assist with the prior authorization process for mometasone/formoterol. Lastly, the pharmacist created a referral to case management to assist the patient in obtaining durable medical equipment and assess their eligibility for a meal benefit.

Outcome

As a result of the pharmacist’s intervention, many of the patient’s medication-related issues were resolved. The patient was given the tools needed to monitor her chronic conditions at home. New prescriptions for furosemide and tiotropium bromide inhaler were sent to and filled at the patient’s pharmacy. The pharmacist was also able to help the pharmacy process the patient’s vitamin D prescription. The prescriber submitted a prior authorization for mometasone/formoterol, and it was approved. All medications were filled consistently post intervention. The patient was also connected to a case manager who was able to help the patient with her durable medication equipment needs and meal benefit.

This is just one example of many, demonstrating how the PerformRx clinical outcomes and therapeutic optimization team can identify and resolve medication-related problems and adverse drug events, and help address social determinants of health. These interactions take place with over 14,000 patients each year, with services and populations expanding yearly. In 2021, the most recent year with data available, there were over 22,000 medication-related problems identified, and over 10,000 of those were resolved successfully. By taking the time to help patients on the individual level, we can continue to help drive improvements in care across the population.

OUR AUTHORS

REFERENCES

1. Hales CM, Servais J, Martin CB, Kohen D. Prescription Drug Use Among Adults Aged 40–79 in the United States and Canada. NCHS Data Brief. 2019;347.

2. Budnitz DS, Shehab N, Lovegrove MC, Geller AI, Lind JN, Pollock DA. US Emergency department visits attributed to medication harms, 2017–2019. JAMA. 2021;326(13):1299-309. doi: 10.1001/jama.2021.13844

3. Institute of Medicine. Committee on Identifying and Preventing Medication Errors. Preventing Medication Errors, Washington, DC: The National Academies Press 2006

4. Zillich, A. J., Snyder, M. E., Frail, C. K., Lewis, J. L., Deshotels, D., Dunham, P., Jaynes, H. A., & Sutherland, J. M. (2014). A Randomized, Controlled Pragmatic Trial of Telephonic Medication Therapy Management to Reduce Hospitalization in Home Health Patients. Health Services Research, 49(5), 1537–1554. https://doi.org/10.1111/1475-6773.12176

5. Miller E., Roane, T. E., & Mclin, K. D. (2016). Reduction of 30-day hospital readmissions after patient-centric telephonic medication therapy management services. Hospital Pharmacy, 51(11), 907-914. doi:10.1310/hpj5111-907

6. Skinner, J. S., Poe, B., Hopper, R., Boyer, A., & Wilkins, C. H. (2015). Assessing the effectiveness of pharmacist-directed medication therapy management in improving diabetes outcomes in patients with poorly controlled diabetes. The Diabetes Educator, 41(4), 459-465. doi:10.1177/0145721715587563

7. Pinto, S. L., Kumar, J., Partha, G., & Bechtol, R. A. (2013). Improving the economic and humanistic outcomes for diabetic patients: Making a case for employer-sponsored medication therapy management. ClinicoEconomics and Outcomes Research, 153. doi:10.2147/ceor.s40735

8. Amanda Foster et al., “Addressing Social Determinants of Health in Community Pharmacy: Innovative Opportunities and Practice Models,” Journal of American Pharmacists Association, 2021.

Alex Ekstrom PharmD PerformRx

Erika Kaplan PharmD PerformRx

Commentary by Megan Coder, PharmD, MBA, Chief Policy Officer, Digital Therapeutic Alliance

In 2017, Digital Therapeutic Alliance (DTA) launched with the goal of creating a strong foundation for this new category of medicine. With digital therapeutics (DTx) being used in patients’ homes and clinical settings around the world to directly treat and alleviate diseases and disorders, it was imperative for industry leaders to align around product development principles [dtxalliance.org], ethical standards [dtxalliance.org], and medical device best practices to ensure that meaningful, safe, and effective therapies are delivered to patients.

As such, DTA continues to deliver on our mission by developing DTx evaluation frameworks [dtxalliance. org] for payers and clinicians to use, supporting the passage of a DTx Medicare benefit category [dtxalliance.org], and clarifying how these products are incorporated into health-system workflows [dtxalliance.org]. Digital therapeutics are becoming a core component of health care delivery.

What are digital therapeutics?

Digital therapeutics (DTx) is an emerging class of therapeutics within digital health solutions. The Digital Therapeutics Alliance (DTA) defines DTx as delivering evidence-based therapeutic interventions to patients that are driven by high quality software programs to treat, manage, or prevent a disease or disorder.

DTx can be used independently or concurrently with medications or other therapies to optimize patient care and outcomes.3 DTx interventions are delivered to patients through digital devices such as a smartphone or tablet. Food and Drug Administration (FDA)authorized digital therapeutics, a subcategory within DTx known as prescription digital therapeutics (PDTs), are evaluated for safety and efficacy and require a prescription from a licensed health care practitioner. The Digital Health Trends 2021 report by IQVIA reported that there were 137 DTx products in the pipeline with 25 DTx products being marketed globally in at least one country.4 Currently in the U.S., 16 DTx products are authorized, of which eight need a prescription.5

Digital health is an all-encompassing term that includes mobile health, health information technology, wearable devices, telehealth, telemedicine, and personalized medicine.1 As stated by the World Health Organization, digital health solutions are an integral part of our daily lives and can be leveraged for global attainment of health and well-being.2 Digital health solutions empower individuals to participate in and manage their health. Fueled by limited access to in-person visits during the COVID-19 pandemic, there has been an increase in utilization of virtual care and other digital health solutions. As comfort levels have increased with the use of digital health at the provider and patient level, we can anticipate that this field of health care will continue to expand.

Like conventional medicines, DTx products treat a range of chronic conditions that include substance use disorders, insomnia, pain, and behavioral health disorders, such as attention deficit hyperactivity disorder (ADHD), depression, and anxiety. Instead of solely relying on medications, DTx uses softwarebased algorithms and machine learning to provide personalized therapy that is tailored for the patient based on their progress, preferences, and feedback. DTx also enables the collection of real-time data allowing for population health management.

Many DTx products on the market today are based on cognitive behavioral therapy (CBT) delivered through a smartphone or tablet. CBT is a form of psychosocial treatment provided over a set period and has demonstrated to be effective for multiple disorders including depression, substance use disorder, insomnia, irritable bowel syndrome, and chronic pain. At present there are five DTx products using CBT as the primary interventions that are FDA-authorized and require prescription.5

Opportunities and challenges in digital therapeutics

DTx can play a significant role in advancing health equity. A Pew research study indicated that 80% of U.S. adults living in rural areas own a smartphone.6 As most DTx interventions are delivered through a smartphone, this treatment modality is uniquely positioned to help lower rural health inequalities by increasing access to care in rural areas. In addition to this, DTx enables patients to have timely access to personalized care when they need it most, such as when they are experiencing symptoms. DTx may also help increase accessibility of care by mitigating the impact of the current shortage of health care practitioners. DTx may also help fill the gap for segments of the population that are looking for alternate ways to manage their health rather than traditional provider office visits.

Unfortunately, even as the number and diversity of products in this category continue to increase, widespread adoption for these products is not following the same trend. The reasons for this include regulation, legislation, coverage, and reimbursement.

At present, digital therapeutics are reviewed under the FDA medical device pathway, including premarket notification [510(k)] and De Novo classification requests.7

De Novo review requires clinical trial data, but it is not as rigorous as what is required for pharmaceutical agents. 510(k) review must demonstrate that the new device is “substantially equivalent” to a predicate device. As the evidence needed for these approval pathways is not as rigorous as the evidence required for pharmaceutical products, real world evidence is needed to drive acceptance and use of these products. The FDA has also created the Digital Health Center of Excellence to guide the review of digital health technology, which will inform future direction for all digital health solutions, including DTx, by supporting the regulatory review of digital health solutions.8

Legislation is needed to pave the path for widespread adoption and continues to evolve. In April 2022, the Centers for Medicare & Medicaid Services (CMS) established new Healthcare Common Procedure Coding System (HCPCS) codes for FDA-authorized PDTs providing CBT interventions, enabling reimbursement through medical benefits.9 On March 8, 2023, a bipartisan bill, Access to Prescription Digital Therapeutics Act of 2023, was introduced to the House of Representatives.10 If passed, the bill will authorize, but not require, CMS to cover digital therapeutics for Medicare and Medicaid beneficiaries. The bill also directs CMS to develop reimbursement and coding practices appropriate to the unique nature of digital therapeutics.

Reimbursement for DTx is not well defined and may fall under pharmacy, medical, behavioral health, or employer-sponsored wellness benefits.11 To promote the use of these products, value-based agreements and pilot projects are also in play. Reimbursement for these products under the pharmacy benefit offers some additional benefits by utilizing established and validated formulary management tools. However, as this a new category of product, currently accepted drug review processes through the pharmacy and therapeutics committee will have to be updated to capture elements relevant to DTx.

Payers, manufacturers, and health care practitioners also must address digital health literacy, cultural considerations, and unique patient circumstances during the development and evaluation process of DTx.

New horizon

DTx has paved the path to a new horizon in health care combining digital technology and evidence-based treatment regimens. If implemented appropriately, DTx has the potential to improve patient outcomes, reduce the cost of care, and advance health equity. There is still work to be done to provide access. The industry must streamline operational steps that are needed to prescribe, and implement care coordination and assessments for patients who need these interventions to assure efficacy and safety. DTx has the potential to empower patients to engage in their personal health care.

OUR AUTHORS

Binal Patel MPharm, BCGP PerformRx

REFERENCES

1. “What is Digital Health”, U.S. FDA, https://www.fda.gov/medical-devices/ digital-health-center-excellence/what-digital-health

2. "Digital Health.” WHO, https://www.who.int/health-topics/digital-health#tab=tab_1

3. “Understanding DTx,” Digital Therapeutics Alliance, https://dtxalliance.org/ understanding-dtx/what-is-a-dtx/

4. "Digital Health Trends 2021,” IQVIA, July 22, 2021, https://www.iqvia.com/insights/ the- iqviainstitute/reports/digital-health-trends-2021

5. "Digital Therapeutics Using Cognitive Behavioral Therapy” IPD Analytics, January 9,2023, http://www.ipdanalytics.com

6. “Mobile Fact Sheet,” Pew Research Center, April 7, 2021, https://www.pewresearch.org/ internet/fact-sheet/mobile/

7. “The Current Landscape and Complexities of Digital Therapeutics” IPD Analytics, August 24, 2021, http://www.ipdanalytics.com

8. “Digital Health Center of Excellence”, U.S. FDA, https://www.fda.gov/medical-devices/ digital-health-center-excellence/about-digital-health-center-excellence

9. “Update - CMS Establishes New Level II HCPCS Code for Certain Digital Therapeutics,” March 2022, http://www.ipdanalytics.com

10. “Prescription Digital Therapeutics.” AMCP, March 9, 2023, https://www.amcp.org/ policy-advocacy/legislative-regulatory-issues/prescription-digital-therapeutics

11. “Prescription Digital Therapeutics: Software-Based Treatments,” IPD Analytics, June 2020, http://www.ipdanalytics.com

DTx enables patients to have timely access to personalized care when they need it most, such as when they are experiencing symptoms.