MRx Clinical Alert - January 2022

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JANUARY 2022

CLINICAL

ALERT YOUR MONTHLY SOURCE FOR DRUG INFORMATION HIGHLIGHTS

EDITORIAL STAFF EDITOR-IN-CHIEF Maryam Tabatabai PharmD EXECUTIVE EDITOR Anna Schreck Bird PharmD

TRENDING TOPICS

COVID-19 TESTING

COVID-19 NOTABLES

DRUG INFORMATION HAPPENINGS & HIGHLIGHTS

PIPELINE NEWS

RECENT FDA APPROVALS

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


TRENDING TOPICS HOT TOPIC: PAXLOVID™ FOR COVID-19

COVID-19: WHITE HOUSE TESTING UPDATE

The US FDA has granted EUA to Pfizer’s Paxlovid (copackaged nirmatrelvir tablets and ritonavir tablets). Paxlovid is authorized for emergency use for the treatment of mildto-moderate COVID-19 in adults and pediatric patients (≥ 12 years of age weighing ≥ 40 kg) with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progression to severe COVID-19, including hospitalization or death. Nirmatrelvir is a SARS-CoV-2 main protease (Mpro) inhibitor, and ritonavir is an HIV-1 protease inhibitor that delays the metabolism of nirmatrelvir. Dosing of Paxlovid is 300 mg (two 150 mg tablets) of nirmatrelvir and one 100 mg tablet of ritonavir taken twice daily for 5 days. Paxlovid is not authorized for treatment in patients requiring hospitalization; for pre- or post-exposure prophylaxis; or for use > 5 consecutive days.

The White House has announced new efforts to expand free at-home OTC tests. By January 15th, the DHHS will issue guidance clarifying that individuals with private insurance who purchase at-home COVID-19 diagnostic tests will be able to be reimbursed by their insurance for the test cost during the Public Health Emergency. To support access in uninsured communities, distribution of free at-home tests will be further expanded through various community sites (health centers, rural clinics), and the number of free tests will be increased.

The EUA is based on data from the randomized, doubleblind, placebo-controlled, phase 2/3 EPIC-HR trial conducted in non-hospitalized adults with symptomatic, laboratory confirmed SARS-CoV-2 within the prior 5 days and ≥ 1 factor associated with an increased risk of developing severe COVID-19. Patients were randomized 1:1 to Paxlovid or placebo orally every 12 hours for 5 days. Individuals with a history of prior COVID-19 infection or vaccination were excluded. The primary endpoint evaluated the proportion of patients who were hospitalized for COVID-19 or died from any cause through day 28. If initiated within 5 days of symptom onset, the primary endpoint was reduced by 88% (0.8% Paxlovid [8/1,039 hospitalized, no deaths] versus 6.3% placebo [66/1,046 hospitalized, 12 deaths]; p<0.0001). When given within 3 days of symptom onset, Paxlovid demonstrated an 89% reduction (p<0.0001) in the primary endpoint compared to placebo with 0.72% (5/697) of Paxlovid patients being hospitalized (no deaths) compared with 6.45% of placebo patients (44/682 hospitalized, 9 deaths). Treatment-emergent AEs were similar between study arms (23% versus 24%, respectively) and were primarily mild. The FDA also recently issued an EUA for another oral antiviral, molnupiravir, from Merck, featured in the December issue of the Clinical Alert. 2 | JANUARY 2022

COVID-19: NOTABLE DEVELOPMENTS The FDA has authorized emergency use of AstraZeneca’s Evusheld™ (tixagevimab copackaged with cilgavimab) administered as 2 separate consecutive IM injections for pre-exposure prophylaxis of COVID-19 in certain adults and pediatric individuals (≥ 12 years old weighing ≥ 40 kg). Evusheld is only authorized for those who are not currently infected with SARS-CoV-2 and who have not recently been exposed to SARS-CoV-2. The authorization also requires that individuals either be moderately to severely immunocompromised or vaccination not be recommended due to severe ADRs to a COVID-19 vaccine/component. The FDA has expanded the EUA of bamlanivimab and etesevimab to include use for all pediatric patients, including newborns, for (1) post-exposure prophylaxis in those at high risk of progression to severe COVID-19 and (2) treatment of mild-to-moderate COVID-19 in those who have a positive COVID-19 test and are at high risk for progression. The FDA has amended the EUA for the Pfizer-Biontech COVID-19 vaccine authorizing use of a single booster dose to those ≥ 12 years of age ≥ 5 months after completion of primary vaccination with the Pfizer-Biontech COVID-19 vaccine. The Janssen COVID-19 Vaccine Fact Sheets have been revised to include a contraindication for those with a history of thrombosis with thrombocytopenia after this vaccine or other adenovirus-vectored COVID-19 vaccines. Please view the end of the publication for the COVID-19 disclaimer.


DRUG INFORMATION

HAPPENINGS & HIGHLIGHTS • Sandoz is recalling 1 lot (SAB06761A, expiration 04/2023) of Enoxaparin Sodium Injection, USP 40 mg/0.4 mL single-dose syringes (NDC 0781-324664) to the consumer level as part of the lot was exposed to a temperature excursion during shipment. Exposure to high temperatures may impact the product’s effectiveness and could increase patients’ risk for blood clots resulting in pain, swelling, stroke, pulmonary embolism, or death due to the patient’s underlying condition. • The FDA has approved an 80 unit/mL formulation of corticotropin by Ani (Purified Cortrophin™ Gel). It is indicated for various rheumatic disorders, collagen diseases, dermatologic diseases, allergic states, ophthalmic diseases, symptomatic sarcoidosis, inducing diuresis or remission of proteinuria in nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus, and acute exacerbations of multiple sclerosis (MS). Launch is expected by early in the 1Q of 2022.

• Product labeling for certain Janus kinase (JAK) inhibitors has been updated to align with new safety information communicated in September 2021 by the FDA regarding the increased risks for serious CV events, cancer, blood clots, and death with these agents. Products impacted include baricitinib (Olumiant®), tofacitinib (Xeljanz®, Xeljanz XR), and upadacitinib (Rinvoq®). The label updates are for the Boxed Warnings, Warnings and Precautions, and Indications for Use for all approved uses (to be used only for certain patients who have not responded or cannot tolerate ≥ 1 tumor necrosis factor [TNF] blocker). The FDA-approved indication for baricitinib already included use only in the 2ndline setting for those who have had an inadequate response to ≥ 1 TNF blocker as did tofacitinib’s UC indication. The safety update is based on data from a large, randomized, safety clinical trial of tofacitinib in RA patients; however, baricitinib and upadacitinib are included in the updates based on their shared mechanism of action with tofacitinib.

DRUG INFORMATION HAPPENINGS • The CDC has endorsed updated recommendations from the Advisory Committee on Immunization Practices (ACIP) on preventing COVID-19 with a preference of an mRNA COVID-19 vaccine over Janssen’s COVID-19 vaccine. • The CDC has published an official health advisory on the new SARS-CoV-2 variant of concern, Omicron. Relatedly, the CDC also has a section on their website on the variant, and the FDA has released a statement on the variant and continues to recommend vaccination and boosters. • The Infectious Diseases Society of America (IDSA) has published guidance on treating antimicrobial-resistant gram-negative infections with a focus on AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenemresistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia infections. • The Institute for Clinical and Economic Review (ICER) has published the final Evidence Report evaluating the clinical effectiveness and value of tezepelumab (Tezspire™; tezepelumab-ekko) for treating severe asthma. • ICER has published the first annual evaluation of barriers to fair access for commercial insurance prescription drug coverage in the US.


PIPELINE

NEWS

UPCOMING PRESCRIPTION DRUG/BIOSIMILAR USER FEE ACT (PDUFA/BsUFA) DATES DRUG NAME MANUFACTURER

FORMULATION THERAPEUTIC CLASS

PROPOSED CLINICAL USE

ANTICIPATED FDA APPROVAL

somatrogon Opko/Pfizer

• SC • Long-acting growth hormone

Pediatric growth hormone deficiency

January 2022

carbetocin Levo

• Intranasal • Oxytocin analog

Prader-Willi syndromerelated hyperphagia and behavioral distress

01/06/2022

daridorexant Idorsia

• Oral • Dual orexin receptor antagonist

Insomnia

01/07/2022

pegfilgrastim (biosimilar to Amgen’s Neulasta®) Amneal

• SC • Leukocyte growth factor

Neutropenia/leukopenia

01/13/2022

oteseconazole Mycovia

• Oral • Azole antifungal

Vulvovaginal candidiasis (recurrent)

01/27/2022

mavacamten Bristol-Myers Squibb

• Oral • Cardiac myosin inhibitor

Symptomatic obstructive hypertrophic cardiomyopathy

01/28/2022

von Willebrand factor, recombinant (Vonvendi®) Takeda

• IV • von Willebrand factor

von Willebrand diseaserelated bleeding prophylaxis

01/28/2022

cemiplimab-rwlc (Libtayo®) Regeneron/Sanofi

• IV • Programmed death receptor-1 (PD-1) inhibitor

Recurrent or metastatic cervical cancer

01/30/2022

faricimab Genentech

• Intravitreal • Angiopoietin-2/vascular endothelial growth factor (VEGF) inhibitor

Diabetic macular edema; Neovascular (wet) age-related macular degeneration

01/31/2022

sutimlimab Sanofi

• IV • Complement inhibitor

Cold agglutinin disease

02/04/2022

4 | JANUARY 2022


RECENT FDA

APPROVALS DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs clindamycin phosphate (Xaciato™) Daré

• • • • •

505(b)(2) NDA approval 12/07/2021; Priority Review Indicated for the treatment of bacterial vaginosis in female patients ≥ 12 years of age Lincosamide antibacterial Vaginal gel: 2% clindamycin in a 25 g tube Recommended dosage is 1 applicatorful (delivers 5 g of gel; 100 mg of clindamycin) once intravaginally as a single dose at any time of the day • Product availability is expected in 2022

finasteride/tadalafil (Entadfi™) Veru

• 505(b)(2) NDA approval 12/09/2021; Standard Review • Indicated to initiate treatment of signs and symptoms of benign prostatic hyperplasia (BPH) in men with an enlarged prostate for up to 26 weeks • 5α-reductase inhibitor/phosphodiesterase 5 (PDE5) inhibitor • Oral capsule: 5 mg finasteride/5 mg tadalafil • Recommended dosage is 1 capsule at the same time once daily for up to 26 weeks without food • Product availability is expected in early 2022

budesonide (Tarpeyo™) Calliditas

• 505(b)(2) NDA approval 12/15/2021; Accelerated Approval, Orphan Drug, Priority Review • Indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN; Berger’s disease) at risk of rapid disease progression, generally a urine proteinto-creatinine ratio (UPCR) ≥ 1.5 g/g; Accelerated Approval was based on reduction in proteinuria; it has not been established if it slows kidney function decline in patients with IgAN; therefore, continued approval may require demonstration of benefit in confirmatory clinical trials • Corticosteroid • Delayed-release oral capsule: 4 mg • Recommended dosage is 16 mg orally once daily, in the morning ≥ 1 hour before a meal for a duration of 9 months; taper dose upon discontinuation; safety and efficacy of subsequent courses of Tarpeyo therapy have not been established • Product availability is expected early in 1Q 2022

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.


RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs continued glycopyrrolate (Dartisla ODT™) Edenbridge

• 505(b)(2) NDA 12/16/2021; Standard Review • Indicated in adults to reduce symptoms of a peptic ulcer as an adjunct to treatment of peptic ulcer • Not indicated as monotherapy for treatment of peptic ulcer because effectiveness in peptic ulcer healing has not been established • Anticholinergic • Orally disintegrating tablet: 1.7 mg • Recommended dosage is 1.7 mg given 2 or 3 times daily administered on top of the tongue; allow to disintegrate and swallow without water ≥ 1 hour before or 2 hours after food; maximum daily dosage of 6.8 mg; the lowest effective dose should be used to control symptoms; patients should be switched to another oral tablet dosage form if they can be titrated to a lower dose of glycopyrrolate; patients who are currently using the 2 mg strength of another oral tablet dosage form of glycopyrrolate can be switched to Dartisla ODT; however, use is not recommended for patients starting treatment or receiving maintenance treatment with a lower strength of another oral glycopyrrolate product (e.g., 1 mg) • Product availability is expected in early 2022

adalimumab-aqvh (Yusimry™) Coherus BioSciences

• BLA approval 12/17/2021; Standard Review; biosimilar to adalimumab (Humira®) • Indicated for certain patients with the following conditions: adults with moderately to severely active RA, moderately to severely active juvenile idiopathic arthritis in patients ≥ 2 years old, adults with active psoriatic arthritis, adults with active ankylosing spondylitis, moderately to severely active Crohn’s disease in patients ≥ 6 years old, adults with moderately to severely active UC (effectiveness has not been established in patients who have lost response/were intolerant to TNF blockers), and adults with moderate to severe chronic plaque psoriasis • TNF blocker • Injection: 40 mg/0.8 mL in a single-dose, prefilled glass syringe • Recommended dosage is based on the patient’s condition, age, and/or body weight given by SC injection under the guidance of a physician; following proper training in injection technique, patients or caregivers may administer if determined appropriate by an HCP and with follow-up, as needed • Boxed Warnings for serious infections and malignancy • Product availability is expected in July 2023

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.

6 | JANUARY 2022


DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs continued efgartigimod alfa-fcab (Vyvgart™) argenx BV

• BLA approval 12/17/2021; Fast Track, Orphan Drug • Indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive • Neonatal Fc receptor blocker • Injection: 400 mg in 20 mL (20 mg/mL) in an SDV • Recommended dosage is 10 mg/kg as an IV infusion over 1 hour by an HCP once weekly for 4 weeks; for patients weighing ≥ 120 kg, the recommended dose is 1,200 mg per infusion; subsequent treatment cycles should be administered based on clinical evaluation; administration of subsequent cycles < 50 days from the start of the prior treatment cycle has not been established; prior to starting a new treatment cycle, assess the need for age-appropriate vaccines based on immunization guidelines

insulin glargine-aglr (Rezvoglar™) Eli Lilly

• BLA approval 12/17/2021; Standard Review; biosimilar to insulin glargine (Lantus®) • Indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes mellitus (T1DM) and in adults with type 2 diabetes mellitus (T2DM) • Not recommended for treating diabetic ketoacidosis • Long-acting human insulin analog • Injection: 100 units/mL (U-100) available as 3 mL single-patient-use Rezvoglar KwikPen® prefilled pen • Recommended dosage is individualized based on metabolic needs, blood glucose (BG) monitoring, glycemic control, diabetes type, and previous insulin use with SC administration into the abdominal area, thigh, or deltoid once daily at any time of day at the same time each day; careful monitoring of BG is recommended when switching to Rezvoglar and during first weeks after switching

tezepelumab-ekko (Tezspire™) AstraZeneca

• BLA approval 12/17/2021; Breakthrough Therapy, Priority Review • Indicated for the add-on maintenance treatment of adult and pediatric patients aged ≥ 12 years with severe asthma • Not for relief of acute bronchospasm or status asthmaticus • Thymic stromal lymphopoietin blocker • Injection: 210 mg/1.91 mL (110 mg/mL) solution in an SDV and single-dose, prefilled syringe • Recommended dosage is 210 mg administered via SC injection into the abdomen, upper arm, or thigh by an HCP once every 4 weeks

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.


RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs continued voxelotor (Oxbryta®) Global Blood Therapeutics

• NDA approval 12/17/2021; Accelerated Approval, Breakthrough Therapy, Orphan Drug, Priority Review • Indicated for the treatment of sickle cell disease (SCD) in adults and pediatric patients ≥ 4 years old; Accelerated Approval is based on increase in hemoglobin (Hb); therefore, continued approval for this indication may require demonstration of benefit in confirmatory clinical trials • Hemoglobin S polymerization inhibitor • Tablet for oral suspension: 300 mg; already approved as 500 mg oral tablet • Recommended dosage is 1,500 mg once daily for patients ≥ 12 years old, and body weight-based dosing for patients 4 to < 12 years old given once daily as follows: ≥ 40 kg: 1,500 mg, 20 kg to < 40 kg: 900 mg, 10 kg to < 20 kg: 600 mg; the appropriate product (tablets or tablets for oral suspension) selection is based on patient’s ability to swallow tablets and patient weight; voxelotor can be taken with or without food and may be given with or without hydroxyurea

cabotegravir (Apretude) ViiV

• NDA approval 12/20/2021; Breakthrough Therapy, Priority Review • Indicated in at-risk adults and adolescents weighing ≥ 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection • HIV-1 integrase strand transfer inhibitor (INSTI) • Injection: 600 mg/3 mL (200 mg/mL) in an SDV • Recommended dosage is a single 600 mg (3 mL) HCP administered gluteal IM injection 1 month apart for 2 consecutive months, continue with the injections every 2 months thereafter; before starting Apretude, an oral lead-in of cabotegravir 30 mg once daily for 28 days can be used to evaluate tolerability • Boxed Warning for risk of drug resistance with use for HIV-1 PrEP in undiagnosed HIV-1 infection; screen for HIV-1 infection immediately before each injection

rivaroxaban (Xarelto®) Janssen

• NDA approval 12/20/2021; Priority Review • Indicated for (1) the treatment of venous thromboembolism (VTE) and reduction in the risk of recurrent VTE in pediatric patients from birth to < 18 years; and (2) thromboprophylaxis in pediatric patients ≥ 2 years old with congenital heart disease after the Fontan procedure • Factor Xa inhibitor • Oral suspension: 1 mg/mL once reconstituted; already approved as oral tablets (2.5 mg, 10 mg, 15 mg, and 20 mg) • Recommended dosage for VTE and reduction in risk of recurrent VTE in pediatric patients is based on body weight taken with food to increase absorption; for thromboprophylaxis in pediatric patients with congenital heart disease after the Fontan procedure dosage is also based on body weight, taken with or without food • Boxed Warnings for premature discontinuation increases the risk of thrombotic events and spinal/epidural hematoma • Product availability is expected in mid-January 2022

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.

8 | JANUARY 2022


DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs continued fingolimod (Tascenso ODT™) Handa Neuroscience

• 505(b)(2) NDA approval 12/23/2021; Standard Review • Indicated for the treatment of relapsing forms of MS, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in pediatric patients ≥ 10 years old and weighing ≤ 40 kg; not approved for use in any patients who weigh > 40 kg • Sphingosine 1-phosphate receptor modulator • Orally disintegrating tablet: 0.25 mg • Recommended dosage is 0.25 mg once daily, with or without food, administered with or without water by placing the tablet directly on the tongue and allow it to dissolve before swallowing; patients who start therapy and those who reinitiate after discontinuation for longer than 14 days, require first-dose monitoring

inclisiran (Leqvio®) Novartis

• NDA approval 12/23/2021; Priority Review • Indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of LDL-C • Effect on CV morbidity and mortality has not been established • Small interfering RNA (siRNA) directed to proprotein convertase subtilisin kexin type 9 (PCSK9) mRNA • Injection: 284 mg/1.5 mL (189 mg/mL) in a single-dose, prefilled syringe • Recommended dosage, in combination with maximally tolerated statin therapy, is 284 mg administered as a single SC injection into the abdomen, upper arm, or thigh by an HCP initially, again at 3 months, and then every 6 months thereafter

tralokinumab-ldrm (Adbry™) Leo

• BLA approval 12/27/2021; Standard Review • Indicated for the treatment of moderate-to-severe atopic dermatitis in adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable; therapy can be used with or without topical corticosteroids • Interleukin-13 antagonist • Injection: 150 mg/mL solution in a single-dose prefilled syringe with needle guard • Recommended dosage is an initial SC dose of 600 mg (four 150 mg injections), followed by 300 mg (two 150 mg injections) SC administered every other week; a dosage of 300 mg every 4 weeks may be considered for patients < 100 kg who achieve clear/almost clear skin after 16 weeks of treatment; intended for use under the guidance of an HCP; patients/caregivers can self-inject following training in SC injection technique; SC injection can be given into the abdomen, upper arm, or thigh • Product availability is expected by February 2022

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.


Glossary: ADR adverse reaction

EUA Emergency Use Authorization

mRNA messenger ribonucleic acid

SDV single-dose vial

AE adverse effect

FDA Food and Drug Administration

NDC National Drug Code

UC ulcerative colitis

CDC Centers for Disease Control and Prevention

HCP healthcare professional

NIH National Institutes of Health

US United States

HIV-1 human immunodeficiency virus-1

OTC over-the-counter

USP United States Pharmacopeia

IM intramuscular

RA rheumatoid arthritis

WHO World Health Organization

SARS-CoV-2 severe acute respiratory syndrome coronavirus 2

COVID-19 Coronavirus Disease 2019 CV cardiovascular DHHS Departments of Health and Human Services

References:

fda.gov

IV intravenous LDL-C low-density lipoprotein cholesterol

SC subcutaneous

whitehouse.gov

COVID-19 Disclaimer: For more resources on COVID-19, visit the Magellan Rx Coronavirus Update webpage. For the most current information, visit the FDA, CDC, NIH, NIH guidelines, and 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. 10 | JANUARY 2022

© 2022, Magellan Health. All rights reserved.


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