MRx Clinical Alert - January 2021

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DEPUTY EDITORS Jessica Czechowski PharmD Lara Frick PharmD, BCPS, BCPP Carole Kerzic RPh Leslie Pittman PharmD

TRENDING TOPICS HOT TOPIC: FDA ISSUES EUAs FOR TWO COVID-19 VACCINES The United States (US) Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for Pfizer-BioNTech’s coronavirus disease 2019 (COVID-19) vaccine and for Moderna’s COVID-19 vaccine. The EUAs allow for the emergency use of both unapproved vaccines for active immunization to prevent COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Pfizer-BioNTech vaccine is authorized for use in individuals ≥ 16 years of age, whereas the Moderna vaccine is authorized for use in individuals ≥ 18 years of age. The vaccines received EUA in December and are suspensions for intramuscular (IM) injection, each requiring a series of 2 doses. The Pfizer-BioNTech vaccine doses are separated by 21 days, while the Moderna vaccine doses are separated by 28 days. Both products are shipped in multiple-dose vials (MDV) but vary in storage requirements. The Pfizer-BioNTech vaccine is shipped in a thermal container with dry ice and requires storage in an ultra-low temperature freezer (-80°C to -60°C) until use. If an ultra-low temperature freezer is not available, the thermal container used for shipping may provide temporary storage through regularly refilling with dry ice. Once thawed, the undiluted vials can be stored in the refrigerator (2°C to 8°C) for up to 5 days. Although the Moderna vials are also stored frozen, the temperature requirement is -25°C to -15°C (standard freezer temperature), and the vaccine should not be stored on dry ice or below -40°C. Additionally, the Moderna vials can be stored under refrigeration from 2°C to 8°C for up to 30 days before use. Both products must be thawed before administering. The Pfizer-BioNTech vaccine requires dilution with 0.9% sodium chloride injection, USP before administration. The Moderna vaccine should not be diluted. Both vaccines utilize a novel messenger ribonucleic 2 | JANUARY 2021

acid (mRNA) platform that allows for expression of the SARS-CoV-2 S antigen, thereby eliciting an immune response to the antigen. As there are currently no data regarding the interchangeability of COVID-19 vaccines, individuals who have received 1 dose of either vaccine should receive a second dose with the same vaccine in order to complete the vaccination series. Both vaccines are contraindicated in individuals with a known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the respective vaccine. Additionally, both vaccines carry a warning stating medical treatment should be immediately available to manage allergic reactions in case an acute anaphylactic reaction occurs following administration. Also, it is stated that immunocompromised individuals (e.g., persons on immunosuppressant therapy) may have a decreased immune response. Furthermore, the vaccines may not protect all vaccine recipients. Adverse reactions were similar between the 2 vaccines and included injection site pain, fatigue, headache, myalgia, arthralgia, chills, fever, injection site swelling and redness, nausea/vomiting, and lymphadenopathy or axillary swelling/tenderness. For both vaccines, additional adverse reactions, some of which could be serious, may be detected with more widespread use. The EUA for the Pfizer-BioNTech vaccine was based on findings from an ongoing, phase 1/2/3 study with efficacy data from 36,523 participants ≥ 12 years old without evidence of SARS-CoV-2 infection that demonstrated vaccine efficacy of 95% ≥ 7 days following the second dose (8 cases in the vaccine arm versus 162 in the placebo arm). The EUA for the Moderna vaccine was based on an ongoing, phase 3 study with efficacy data from 28,207 participants ≥ 18 years old without evidence of SARSCoV-2, demonstrating vaccine efficacy of 94.1% ≥ 14 days after the second dose (11 cases in the vaccine arm versus 185 in the placebo arm).

TRENDING TOPICS continued Under Operation Warp Speed (OWS), the Department of Defense (DoD), the Centers for Disease Control and Prevention (CDC), and the Department of Health and Human Services (HHS) are partnering to coordinate allocation and distribution of vaccines. This complex logistical process requires rigorous stock management and temperature control. For details on vaccine allocation, view the COVID-19 Notable Developments section.

BEHAVIORAL HEALTH CORNER: DIGITAL HEALTH TECHNOLOGIES FOR OUD The Institute for Clinical and Economic Review (ICER) has released the final evidence report on the use of digital health technologies (DHT) as an adjunct to medication-assisted therapy (MAT) for opioid use disorder (OUD). In the US, OUD continues to be a public health crisis. Drug overdose deaths have increased continually until a plateau in 2017 of about 70,000 deaths per year followed by a continued increase in 2018 and 2019. MAT is considered to be the most effective treatment; however, greater than half of MAT patients initiating therapy discontinue within 3 to 6 months. Although behavioral therapies (BT) have demonstrated the ability to increase patient retention, BT require extensive resources. DHT could potentially increase BT availability and decrease costs. The ICER review assessed 3 DHT that are digital applications (app): reSET-O®, Connections, and DynamiCare. ReSET-O is a 12-week program utilized with buprenorphine and small rewards. Connections allows for communication with addiction experts and support groups and has a 7-session program focused on cognitive and behavioral skills. DynamiCare is comprised of 36 classroom-based training sessions with monitoring for substance use and debit card rewards for negative drug screenings and attending appointments. According to ICER, although none of the 3 DHT currently have published, randomized trials showing if the app increases abstinence or retention in MAT, DHT are unlikely to result in harm, and are therefore, at worst, equivalent to using MAT alone. Limited data on the training and incentives utilized by the DHT suggest these DHT may provide small incremental benefits in retention. Based on this, ICER designated all 3 DHT an ICER evidence rating of “C+” (comparable or incremental).

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COVID-19: NOTABLE DEVELOPMENTS The CDC has released a COVID-19 Vaccination Program Interim Playbook regarding public health preparedness planning for vaccine distribution. It details a 3-phased approach to COVID-19 vaccine allocation. In phase 1, there will be limited supply of available vaccine, and vaccination efforts should focus on at-risk populations and essential workers. In phase 2, a larger number of vaccine doses will be available, allowing for vaccinations to be expanded to the general population and also an expanded provider network. Phase 3 will likely see a sufficient supply of the vaccine for the entire population. Populations of focus for initial vaccination during phase 1 include: • phase 1a – healthcare personnel and long-term care facility residents • phase 1b – non-healthcare front-line essential workers (e.g., police officers, firefighters, education sector, food/agriculture workers, manufacturing, corrections officers) and adults ≥ 75 years old • phase 1c – adults 65 to 74 years old, individuals 16 to 64 years old with high-risk medical conditions, and other essential workers The CDC also offers interim clinical considerations for use of the mRNA-based Moderna and PfizerBioNTech COVID-19 vaccines. Vaccination of special populations (e.g., immunocompromised, pregnant) are among the variety of clinical considerations addressed by the CDC. This content will be updated routinely. The American College of Obstetricians and Gynecologists (ACOG) also offers guidance on use of the vaccines in pregnant and lactating patients. Public health measures, such as masks, social distancing, and hand hygiene, remain among the measures to prevent and control infection. For more resources on COVID-19, visit the Magellan Rx Coronavirus Update webpage. For the most current information, visit the FDA, the CDC, the Infectious Diseases Society of America (IDSA) guidelines, the National Institutes of Health (NIH), the NIH guidelines, and World Health Organization (WHO) websites. State and local health departments also provide valuable information regarding management in local communities. As the COVID-19 landscape is fluid, assumptions are subject to change.


HAPPENINGS & HIGHLIGHTS • The CDC has reported influenza activity for the week ending January 2, 2021 continues to be lower than usual for early January. Six jurisdictions are reporting low influenza-like illness (ILI) and all other jurisdictions are reporting minimal ILI; however, data should be interpreted carefully due to the potential impact of COVID-19. As of December 22, 2020, no shortages are being reported for antiviral medications. • Avkare has issued a voluntary recall for 1 lot of sildenafil 100 mg tablets (lot 36884; expiration date 03/2022) and 1 lot of trazodone 100 mg tablets (lot 36783; expiration date 06/2022) to the consumer level. The recall is being initiated due to a product mix-up resulting in the drugs being inadvertently packaged together during bottling. To date, no recall related adverse events have been reported. • Torrent issued a voluntary recall of 1 lot of anagrelide capsules, USP, 1 mg, 100-count bottles (lot BFD1G001; expiration 12/2021) to the consumer level as the dissolution test failed during regular quality assessment. No adverse effects have been reported.

• MPM Medical has voluntarily recalled 1 lot of Regenecare® HA Hydrogel (2% lidocaine hydrochloride [HCl]) to the consumer level due to Burkholderia cepacia contamination. The recall was initiated after 2 customer complaints of visible contamination. Topical use of affected product may lead to local skin infections. This over-the-counter (OTC) product is used for temporary relief of pain and itching due to minor burns and cuts, sunburns, scrapes, insect bites, or other minor skin irritations. • The FDA has issued a statement that sitagliptin (Januvia®), sitagliptin/metformin HCl (Janumet®), and sitagliptin/ metformin HCl extended-release (ER) (Janumet® XR) have not demonstrated the ability to improve glycemic control in patients 10 to 17 years old with type 2 diabetes. Findings from 3 double-blind, placebocontrolled clinical trials conducted over 54 weeks in 410 patients did not demonstrate sitagliptin provided a significant difference in hemoglobin A1c (HbA1c) compared to placebo. Corresponding updates have been made to the products’ labeling.

DRUG INFORMATION HAPPENINGS • The American Heart Association/American College of Cardiology (AHA/ACC) have issued guidelines for the management of patients with hypertrophic cardiomyopathy (HCM). • The IDSA, American Academy of Neurology (AAN), and American College of Rheumatology (ACR) have released 2020 guidelines on preventing, diagnosing, and treating Lyme disease. • The NIH has published a focused update to the guidelines on asthma diagnosis, management, and treatment. The guidelines detail individualized treatment modalities for various age groups based on disease severity. • The US Preventive Services Task Force (USPSTF) has issued a final recommendation on high blood pressure screening in children and adolescents. Currently, evidence is inadequate to determine the benefits and risks of screening for high blood pressure in this patient population (grade I: insufficient evidence).

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cabotegravir + rilpivirine Viiv

• IM • Integrase strand transfer inhibitor (INSTI) + nonnucleoside reverse transcriptase inhibitor (NNRTI)

Human immunodeficiency virus 1 (HIV-1) infection treatment

Jan-Mar 2021

pegfilgrastim (biosimilar to Amgen’s Neulasta®) Merck/Fresenius

• SC • Colony-stimulating factor (CSF)


Jan-Mar 2021

tepotinib Merck

• Oral • C-met tyrosine kinase inhibitor

Non-small cell lung cancer

Jan-Mar 2021

naloxone Hikma

• Intranasal • Opioid antagonist

Opioid overdose

Jan-Apr 2021

vericiguat Merck/Bayer

• Oral • Guanylate cyclase stimulant

Chronic heart failure


voclosporin Aurinia

• Oral • Calcineurin inhibitor

Lupus nephritis


romiplostim (Nplate®) Amgen

• SC • Thrombopoietin receptor agonist

Hematopoietic syndrome of acute radiation syndrome


evinacumab Regeneron

• IV • Anti-angiopoietin-like protein 3 (ANGPTL3) antibody

Homozygous familial hypercholesterolemia


trilaciclib G1 Therapeutics/ Boehringer Ingelheim

• IV • Cyclin dependent kinase (CDK) 4/6 dual inhibitor

Prevention of myelosuppression associated with small cell lung cancer chemotherapy


umbralisib TG Therapeutics

• Oral • Phosphoinositide 3-kinase (PI3K) inhibitor

Marginal zone lymphoma


IM = intramuscular; IV = intravenous; SC = subcutaneous




New Drugs levothyroxine sodium (Thyquidity™) VistaPharm

• 505(b)(2) NDA approval 11/30/2020 • Indicated for 1) hypothyroidism as replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism and for 2) pituitary thyrotropin (thyroid-stimulating hormone [TSH]) suppression as an adjunct to surgery and radioiodine therapy in the management of thyrotropindependent well-differentiated thyroid cancer • Not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients; also not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis • Thyroid hormone • Oral solution: 100 mcg/5 mL (20 mcg/mL) in 100 mL bottle • Recommended dosage is based on a variety of factors (e.g., patient age, body weight, cardiovascular status, other medical conditions, concurrent medications, the condition being treated); administered as a single daily dose ideally on an empty stomach 30 to 60 minutes prior to breakfast via a calibrated oral syringe; peak therapeutic effect may not occur for 4 to 6 weeks • Boxed warning that product is not for treatment of obesity or for weight loss

tasimelteon (Hetlioz LQ™) Vanda

• NDA approval 12/01/2020; Orphan Drug, Priority Review • Indicated for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in pediatric patients 3 years to 15 years old • Melatonin receptor agonist • Oral suspension: 4 mg/mL in a bottle of 48 mL or 158 mL; store refrigerated; not substitutable with the oral capsules • Recommended dosage is based on patient’s body weight taken 1 hour prior to bedtime, at the same time each night without food; for patients ≤ 28 kg, the recommended daily dose is 0.7 mg/kg, and for patients > 28 kg, the recommended daily dose is 20 mg • Product availability is expected in 1Q 2021

ANDA = Abbreviated New Drug Application; BLA = Biologics License Application; H = Half; NDA = New Drug Application; Q = Quarter; sBLA = Supplemental Biologics License Application; sNDA = Supplemental New Drug Application; 505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.

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New Drugs continued berotralstat (Orladeyo™) BioCryst

• NDA approval 12/03/2020; Orphan Drug • Indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients ≥ 12 years of age • Not indicated for the treatment of acute HAE attacks • Plasma kallikrein inhibitor • Oral capsule: 110 mg and 150 mg • Recommended dosage is 150 mg orally once daily with food; 110 mg once daily with food is recommended in patients with hepatic impairment, concomitant use with P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) inhibitors, or persistent gastrointestinal reactions

tirbanibulin (Klisyri®) Almirall

• NDA approval 12/14/2020 • Indicated for the topical treatment of actinic keratosis of the face or scalp • Microtubule inhibitor • Topical ointment: 1% in 250 mg single-dose packets • Apply to affected areas of face or scalp once daily for 5 consecutive days using 1 single-dose packet per application • Product availability is expected 1Q 2021

margetuximab-cmkb (Margenza™) Macrogenics

• BLA approval 12/16/2020; Assessment Aid, Fast Track • Indicated for use, in combination with chemotherapy, for the treatment of adults with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer who have received ≥ 2 prior anti-HER2 regimens, ≥ 1 of which was for metastatic disease • HER2/neu receptor antagonist • Injection: 250 mg/10 mL single-dose vial (SDV) • Recommended dosage is 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity; administered as an intravenous (IV) infusion after dilution by a healthcare professional (HCP) with the initial dose given over 2 hours and subsequent doses over ≥ 30 minutes • Boxed warning for left ventricular dysfunction and embryofetal toxicity • Product availability is expected in March 2021

ANDA = Abbreviated New Drug Application; BLA = Biologics License Application; H = Half; NDA = New Drug Application; Q = Quarter; sBLA = Supplemental Biologics License Application; sNDA = Supplemental New Drug Application; 505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.



New Drugs continued rituximab-arrx (Riabni™) Amgen

• BLA approval 12/17/2020; biosimilar to Genentech’s Rituxan® • Indicated for the treatment of select adult patients with non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), or granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) • CD20-directed cytolytic antibody • Injection: 10 mg/mL concentration in 10 mL and 50 mL SDV • Recommended dosage varies based on specific diagnosis; administered as an IV infusion by an HCP » NHL – 375 mg/m2 IV, frequency and duration is dependent on specific type of NHL » CLL – 375 mg/m2 IV in the first cycle and 500 mg/m2 in cycles 2 through 6, in combination with fludarabine and cyclophosphamide, administered every 28 days » GPA and MPA – induction dose, in combination with glucocorticoids, is 375 mg/m2 IV once weekly for 4 weeks; follow up dosage in patients who have achieved disease control with induction treatment, in combination with glucocorticoids, is two 500 mg IV infusions separated by 2 weeks, followed by a 500 mg IV infusion every 6 months thereafter, based on clinical evaluation • Boxed warning for fatal infusion-related reactions, severe mucocutaneous reactions, hepatitis B virus reactivation, and progressive multifocal leukoencephalopathy

relugolix (Orgovyx™) Myovant

• NDA approval 12/18/2020; Priority Review • Indicated for the treatment of adult patients with advanced prostate cancer • Gonadotropin-releasing hormone (GnRH) receptor antagonist • Tablet: 120 mg • Recommended dosage includes a loading dose of 360 mg orally on day 1, followed by 120 mg once daily thereafter

vibegron (Gemtesa®) Urovant

• NDA approval 12/23/2020 • Indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults • Beta-3 adrenergic agonist • Tablet: 75 mg • Recommended dosage is 75 mg once daily swallowed whole with water or can be crushed and mixed with applesauce • Product availability is expected late in 1Q 2021

ANDA = Abbreviated New Drug Application; BLA = Biologics License Application; H = Half; NDA = New Drug Application; Q = Quarter; sBLA = Supplemental Biologics License Application; sNDA = Supplemental New Drug Application; 505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.


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