MRx Clinical Alert - July 2021

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JULY 2021

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 UPDATE

PIPELINE NEWS

RECENT FDA APPROVALS

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

DRUG INFORMATION HAPPENINGS & HIGHLIGHTS


TRENDING TOPICS HOT TOPIC: NEW ALZHEIMER’S DRUG The US FDA has approved Biogen’s monoclonal antibody, aducanumab-avwa (Aduhelm™), for the treatment of Alzheimer’s disease (AD). Aducanumab-avwa is an amyloid beta-directed antibody that received Accelerated Approval on the basis of reducing amyloid beta plaques; as a result, the FDA is requiring a new RCT to verify the clinical benefit. It is estimated more than 6 million Americans have AD, an irreversible, progressive brain condition characterized by amyloid plaques and neurofibrillary or tau tangles leading to changes in cognition and memory. Aducanumab-avwa is the first therapy to target the underlying pathology to be approved for AD and the first new treatment for AD in 18 years. The agent is administered by an HCP as a 1-hour IV infusion every 4 weeks and requires titration at initiation to a recommended dose of 10 mg/kg. Efficacy data was based on 3 double-blind, randomized, placebo-controlled studies (n=3,482) that showed aducanumab-treated patients had significant decreases in amyloid beta plaques compared to patients who received the control. Based on this surrogate endpoint, the FDA stated the decrease in plaques is reasonably likely to lead to a clinical benefit. However, only one of two phase 3 studies met the primary endpoint of decreasing clinical decline. Previously, the FDA’s advisory panel voted against FDA approval due to unconvincing data; the agency is not required to follow the advisory panel’s recommendations but often does. Aducanumab-avwa carries a warning for amyloid-related imaging abnormalities (ARIA) including ARIA-edema (ARIA-E) and ARIA-hemosiderin deposition (ARIA-H); therefore, a brain MRI is required at baseline and before the 7th and 12th infusions to assess for asymptomatic ARIA. Additionally, clinical vigilance is recommended during therapy initiation, especially during titration, as symptoms suggestive of ARIA warrant further evaluation and potentially an MRI. If symptomatic ARIA is confirmed, careful assessment is required before therapy is continued. 2 | JULY 2021

ICER has expressed concerns regarding the approval of aducanumab-avwa as approval was based on a surrogate endpoint and the agent carries a potential for serious AEs (ARIA-E and/or ARIA-H). Additionally, aducanumab-avwa has only been studied in patients with mild cognitive impairment (MCI) and mild dementia with confirmed amyloid pathology, but approval was granted to all patients with AD. ICER plans to host a public meeting on July 15, 2021 to address further questions about aducanumab-avwa, including fair pricing.

COVID-19 NOTABLE DEVELOPMENTS The FDA has granted an EUA to an additional investigational monoclonal antibody, GlaxoSmithKline’s sotrovimab, for mild-to-moderate COVID-19 (nonhospitalized) 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. Moderna has submitted to the FDA for expanded use of its COVID-19 vaccine to include adolescents based on the phase 2/3 TeenCOVE study. The FDA has authorized an extension to refrigerated storage (2°C to 8°C) of thawed, undiluted Pfizer-BioNTech COVID-19 vaccine for up to 1 month (previously up to 5 days), and the FDA has extended Janssen’s COVID-19 vaccine shelf-life from 3 months to 4.5 months when stored under refrigeration. The AHA/ASA has released a statement that COVID-19 vaccine benefits continue to outweigh risks, despite rare reports of young adults developing myocarditis following receipt of an mRNA COVID-19 vaccine. For more resources on COVID-19, visit the Magellan Rx Coronavirus Update webpage. For the most current information, visit the FDA, the CDC, the NIH, the 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.


DRUG INFORMATION

HAPPENINGS & HIGHLIGHTS • The FDA has issued a Drug Safety Communication regarding the use of obeticholic acid (Ocaliva®) in patients with primary biliary cholangitis (PBC) with advanced cirrhosis of the liver due to the risk of serious hepatic failure, including a need for liver transplant. Since its Accelerated Approval 5 years ago, the agency has identified 25 cases of liver decompensation or failure. The FDA is requiring updates to the PI, including a new contraindication and revisions to the boxed warning to not use it in PBC patients with advanced cirrhosis. • The Risk Evaluation and Mitigation Strategy (REMS) Program for the injectable opioid antagonist naltrexone ER (Vivitrol®) for injection site reactions has been removed. The REMS was removed as the program was found to have met its goals. However, the Medication Guide will remain available. • The FDA has approved a new oral loading dose regimen for omadacycline (Nuzyra®) for community-acquired bacterial pneumonia (CABP). Previously, the injectable formulation was required to provide the loading dose in CABP patients.

• The US Preventive Services Task Force (USPSTF) has issued final recommendations regarding colorectal cancer (CRC) screening and recommends screening for CRC in all adults 50 to 75 years old (grade A) and 45 to 49 years old (grade B). • Pneumococcal 20-valent conjugate vaccine (Prevnar 20™) was approved for prevention of pneumonia and invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F in adults ≥ 18 years old. Prevnar 20 is administered as a single 0.5 mL IM dose. Certain serotypes included in the vaccine were approved under Accelerated Approval; therefore, continued approval for these serotypes may require demonstration of benefit in confirmatory clinical trials. Pfizer’s Prevnar 20 contains the 13 serotypes included in pneumococcal 13-valent conjugate vaccine, diphtheria CRM197 protein (Prevnar 13®), as well as 7 additional serotypes. The CDC’s Advisory Committee on Immunization Practices (ACIP) will convene in October to update pneumococcal vaccine recommendations for adults.

DRUG INFORMATION HAPPENINGS • The American College of Gastroenterology (ACG) has published updated clinical guidelines on the prevention, diagnosis, and treatment of Clostridioides difficile infections (CDI); guidelines were last published in 2013 by ACG. • The AHA/ASA has published updated guidelines for prevention of stroke in patients with stroke and transient ischemic attacks; guidelines were last published on this topic by AHA/ASA in 2014. • The CDC has updated US Selected Practice Recommendations for Contraceptive Use. • ICER has published a protocol evaluating drug coverage policies’ alignment with fair access standards. This first annual assessment of “Barriers to Fair Access” is expected to be published on October 20, 2021. • ICER has published a final evidence report on the effectiveness and value of 3 new therapies for heavily pretreated patients with triple class refractory multiple myeloma (MM) who had received multiple prior therapies: idecabtagene vicleucel (Abecma®), ciltacabtagene autoleucel (investigational), and belantamab mafodotin-blmf (Blenrep).


PIPELINE

NEWS

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

FORMULATION THERAPEUTIC CLASS

PROPOSED CLINICAL USE

ANTICIPATED FDA APPROVAL

insulin aspart (biosimilar to Novo Nordisk’s Novolog®) Viatris (Mylan)/Biocon

• SC • Rapid-acting human insulin analog

Type 1 and/or 2 diabetes mellitus

July 2021

tanezumab Pfizer/Eli Lilly

• IV • Nerve growth factor (NGF) receptor inhibitor

Osteoarthritis pain

July 2021

abrocitinib Pfizer

• Oral • Janus kinase inhibitor

Atopic dermatitis (moderate to severe)

Jul-Aug 2021

atogepant Abbvie

• Oral • Calcitonin gene-related peptide (CGRP) inhibitor

Episodic migraine prevention

Jul-Aug 2021

teplizumab Provention Bio

• IV • Anti-CD3 antibody

Diabetes mellitus type 1 delay/ prevention

07/02/2021

anifrolumab AstraZeneca/BristolMyers Squibb

• IV • Type 1 interferon inhibitor

Systemic lupus erythematosus

07/05/2021

avacopan Chemocentryx

• Oral • Complement 5a receptor inhibitor

Antineutrophil cytoplasmic antibody-associated vasculitis

07/07/2021

finerenone Bayer

• Oral • Mineralocorticoid receptor antagonist

Diabetic nephropathy

07/09/2021

odevixibat Albireo

• Oral • Apical sodium-dependent bile acid transporter inhibitor

Progressive familial intrahepatic cholestasis

07/20/2021

retifanlimab Incyte

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

Anal cancer

07/23/2021

sulopenem etzadroxil/ probenecid Iterum

• Oral • Beta-lactam antibiotic/uricosuric and renal tubular transport blocker

Uncomplicated urinary tract infection (quinolone-resistant)

07/23/2021

4 | JULY 2021


RECENT FDA

APPROVALS DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs leuprolide mesylate (Camcevi™) Forsee

• 505(b)(2) NDA approval 05/25/2021; Standard Review • Indicated for the treatment of adult patients with advanced prostate cancer • Gonadotropin-releasing hormone (GnRH) agonist • Ready-to-use SC depot injection: 42 mg • Recommended dosage is 42 mg administered as SC injection every 6 months by an HCP

relugolix/estradiol/ norethindrone acetate (Myfembree®) Myovant

• 505(b)(2) NDA approval 05/26/2021; Standard Review • Indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women • Use should be limited to 24 months due to risk of continued and possibly irreversible bone loss • Combination of a GnRH receptor antagonist, an estrogen, and a progestin • Fixed-dose oral tablet (relugolix/estradiol/norethindrone acetate): 40 mg/1 mg/ 0.5 mg • Recommended dosage is 1 tablet orally once daily • Boxed warning for thromboembolic disorders and vascular events

infigratinib (Truseltiq™) QED Therapeutics

• NDA approval 05/28/2021; Accelerated Approval, Assessment Aid, Fast Track Designation, Orphan Drug, Priority Review, Project Orbis, Real-Time Oncology Review (RTOR) • Indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor (FGFR) 2 fusion or other rearrangement, as detected by an FDA-approved test; the presence of an FGFR2 fusion or rearrangement should be confirmed before starting therapy • Kinase inhibitor of FGFR • Oral capsule: 25 mg and 100 mg • Recommended dosage is 125 mg orally once daily on an empty stomach for 21 consecutive days followed by 7 days off therapy, in 28-day cycles continued until disease progression or unacceptable toxicity

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 olanzapine/samidorphan (Lybalvi™) Alkermes

• 505(b)(2) NDA approval 05/28/2021; Standard Review • Indicated for the treatment of 1) schizophrenia in adults and 2) bipolar I disorder in adults for the acute treatment of manic or mixed episodes as monotherapy and as adjunct to lithium or valproate as well as for maintenance monotherapy • Combination of atypical antipsychotic and opioid antagonist • Oral tablet (olanzapine/samidorphan): 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg, and 20 mg/10 mg • Recommended starting dose varies by indication: 5 mg/10 mg to 15 mg/10 mg • Boxed warning for increased mortality in elderly patients with dementia-related psychosis • Product availability is expected in 4Q 2021

sotorasib (Lumakras™) Amgen

• NDA approval 05/28/2021; Accelerated Approval, Breakthrough Therapy, Fast Track, Orphan Drug, Priority Review, Project Orbis • Indicated for the treatment of adult patients with Kirsten rat sarcoma viral oncogene homologue (KRAS) G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received ≥ 1 prior systemic therapy • Inhibitor of the RAS GTPase family • Oral tablet: 120 mg • Recommended dosage is 960 mg (8 tablets) orally once daily until disease progression or unacceptable toxicity • FDA also approved companion diagnostics

posaconazole delayedrelease oral suspension (Noxafil® PowderMix) Merck

• NDA approval 05/31/2021; Standard Review • Indicated for the prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy for pediatric patients ≥ 2 years of age weighing ≤ 40 kg • Azole antifungal • Mixing kit for delayed-release oral suspension: 300 mg • Recommended dosing for pediatric patients is weight-based and is administered twice daily on the first day (loading dose) and then once daily thereafter; dosing ranges from 90 mg (3 mL) for those 10 kg to < 12 kg to 240 mg (8 mL) for those 36 kg to 40 kg

ibrexafungerp (Brexafemme®) Scynexis

• NDA approval 06/01/2021; Priority Review • Indicated for the treatment of adult and post-menarchal pediatric females with vulvovaginal candidiasis (VVC) • Triterpenoid antifungal • Oral tablet: 150 mg • Recommended dosage is 300 mg twice a day for one day, for a total treatment dosage of 600 mg • Product availability is expected in 2H 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.

6 | JULY 2021


RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs continued plasminogen, humantvmh (Ryplazim®) Prometic Bioproduction

• BLA approval 06/04/2021; Fast Track, Orphan Drug, Priority Review, Rare Pediatric Disease Designation • Indicated for the treatment of patients with plasminogen deficiency type 1 (hypoplasminogenemia) • Plasma-derived human plasminogen • Injection: SDV containing 68.8 mg of plasminogen lyophilized powder for reconstitution; after reconstitution, each vial will contain 5.5 mg/mL of plasminogen • Recommended dosage is 6.6 mg/kg of body weight IV every 2 to 4 days; may be selfadministered after training and demonstrating the ability to safely and independently administer

semaglutide (Wegovy™) Novo Nordisk

• NDA approval 06/04/2021; Priority Review • Indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in adults with an initial BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and ≥ 1 weight-related comorbid condition (e.g., HTN, T2DM, dyslipidemia) • Should not be used with other semaglutide-containing agents or other GLP-1 receptor agonists; safety and efficacy of use with other products for weight loss have not been determined; not studied in patients with a history of pancreatitis • GLP-1 receptor agonist; semaglutide is also distributed as brand Ozempic®, a weekly SC injection, and Rybelsus®, a daily oral tablet; both are approved for T2DM; Ozempic is also indicated to reduce CV events in adults with T2DM and established CVD • Solution in single-dose prefilled pen: 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg • Recommended starting dose is 0.25 mg SC injection once weekly for 4 weeks, may increase at 4-week intervals to maximum of 2.4 mg per week; patient- or caregiveradministered following training on proper injection technique • Boxed warning for risk of thyroid C-cell tumors

glecaprevir/pibrentasvir (Mavyret®) Abbvie

• NDA approval 06/10/2021; Orphan Drug, Priority Review • Indicated for the treatment of pediatric patients ≥ 3 years old with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) and for the treatment of pediatric patients ≥ 3 years old with HCV genotype 1 infection who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor but not both • HCV NS3/4A protease inhibitor and an HCV NS5A inhibitor • Oral pellets (glecaprevir/pibrentasvir): packets of 50 mg/20 mg; oral pellets are recommended for pediatric patients 3 years old to < 12 years old weighing < 45 kg; patients ≥ 45 kg or ≥ 12 years old would receive the oral tablets • Recommended dosage for pediatric patients 3 years old to < 12 years old is based on body weight taken once daily with food, sprinkled on a small amount of soft food with a low water content (e.g., peanut butter, chocolate hazelnut spread, cream cheese, thick jam, Greek yogurt) and swallowed without chewing or crushing • Boxed warning for risk of hepatitis B virus (HBV) reactivation in patients coinfected with HCV and HBV

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.

7 | JULY 2021


RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs continued sofosbuvir/velpatasvir (Epclusa®) Gilead

• NDA approval 06/10/2021; Orphan Drug, Priority Review • Indicated for the treatment of pediatric patients ≥ 3 years old with chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection 1) without cirrhosis or with compensated cirrhosis or 2) with decompensated cirrhosis for use in combination with ribavirin • HCV nucleotide analog NS5B polymerase inhibitor and an HCV NS5A inhibitor • Oral pellets (sofosbuvir/velpatasvir): packets of 200 mg/50 mg and 150 mg/37.5 mg • Recommended dosage for pediatric patients ≥ 3 years old is based on body weight and is administered once daily, taken directly in the mouth or with food by sprinkling the oral pellets on ≥ 1 spoonful of non-acidic soft food (e.g., pudding, chocolate syrup, ice cream); swallow without chewing; in patients < 6 years old, administer the pellets with food to increase tolerability and palatability • Boxed warning for risk of HBV reactivation in patients coinfected with HCV and HBV

torsemide (Soaanz®) Sarfez

• 505(b)(2) NDA approval 06/14/2021; Standard Review • Indicated in adults for the treatment of edema associated with heart failure or renal disease • Loop diuretic • Oral tablet: 20 mg and 60 mg • Recommended initial dose is 20 mg once daily with titration by doubling the dose until desired therapeutic response is achieved; doses > 200 mg have not been evaluated

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: AE adverse effect

ER extended-release

HTN hypertension

RCT randomized controlled trial

AHA American Heart Association

EUA Emergency Use Authorization

ICER Institute for Clinical and Economic Review

SARS-CoV-2 severe acute respiratory syndrome coronavirus 2

FDA Food and Drug Administration

IM intramuscular

SC subcutaneous

GLP-1 glucagon-like peptide-1

IV intravenous

SDV single dose vial

MRI magnetic resonance imaging

T2DM type 2 diabetes mellitus

mRNA messenger ribonucleic acid

US United States

ASA American Stroke Association BMI body mass index CDC Centers for Disease Control and Prevention COVID-19 Coronavirus Disease 2019

GVHD graft-versus-host disease

CV cardiovascular

HSCT hematopoietic stem cell transplant

CVD cardiovascular disease

References:

fda.gov

8 | JULY 2021

heart.org

HCP healthcare professional

icer.org

NIH National Institutes of Health PI prescribing information

uspreventiveservicestaskforce.org © 2021, Magellan Health. All rights reserved.

WHO World Health Organization