Clinical Alert - February 2023

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FEBRUARY 2023

C LINICAL

ALERT

Your Monthly Source for Drug Information Highlights

EDITORIAL STAFF

EDITOR-IN-CHIEF

Maryam Tabatabai

PharmD

EXECUTIVE EDITOR

Anna Schreck Bird PharmD

DEPUTY EDITORS

Jessica Czechowski PharmD

Carole Kerzic

RPh

Olivia Pane PharmD, CDCES

Leslie Pittman PharmD

Devon Trumbower PharmD, BCPS

TRENDING TOPICS

BIOSIMILAR CORNER

COVID-19 NOTABLES

DRUG INFORMATION HAPPENINGS & HIGHLIGHTS

PIPELINE NEWS

RECENT FDA APPROVALS

TRENDING TOPICS

NEW ALZHEIMER’S DISEASE DRUG APPROVED

Eisai’s lecanemab-irmb (Leqembi™), an amyloid betadirected antibody, has received Accelerated Approval for the treatment of certain patients with Alzheimer’s disease. Labeling states treatment should be started in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on starting treatment at earlier or later stages of the disease. Accelerated Approval was based on reduction in amyloid beta plaques seen in patients treated with lecanemab-irmb; therefore, continued approval for this use may require demonstration of benefit in a confirmatory clinical trial.

It is supplied as a solution in an SDV (500 mg/5 mL and 200 mg/2 mL) with recommended dosage of 10 mg/kg IV infusion over about 1 hour once every 2 weeks. The presence of amyloid beta pathology should be confirmed before starting therapy, and brain MRI should be obtained within 1 year before starting therapy to assess for preexisting amyloid related imaging abnormalities (ARIA). Additional MRIs should be performed before the 5th, 7th, and 14th infusions to assess for ARIA.

Approval was based on a phase 2, double-blind, placebocontrolled, parallel-group, dose-finding, 79-week study

The primary endpoint of change from baseline on ADCOMS (an Alzheimer’s disease composite score used in the trial) at 12 months did not meet the prespecified success criterion demonstrating a slowing of progression. However, a secondary endpoint — assessing the change from baseline to month 18 in amyloid PET SUVR in a subset of patients — showed a reduction of amyloid beta plaques in patients who received lecanemab-irmb 10 mg/kg every 2 weeks compared to placebo (p<0.0001). The most common ADRs were infusion-related reactions, headache, and ARIA-edema. Due to the Accelerated Approval , an RCT is required by the FDA to confirm clinical benefit. This phase 3 study, Clarity AD, has been completed and submitted to the FDA. Lecanemab-irmb is the second amyloid beta-directed antibody to receive Accelerated Approval; aducanumab-avwa (Aduhelm®) received FDA approval in June 2021.

BIOSIMILAR CORNER: AMJEVITA™ LAUNCH

At the end of January 2023, adalimumab-atto (Amjevita) launched on the US market. This biosimilar to adalimumab (Humira®) was FDA approved in September 2016. The launch marks the first biosimilar to adalimumab to become commercially available in the US. To date, 8 biosimilars to Humira have received FDA approval. Amjevita, a TNF blocker, is approved as a single-dose prefilled SureClick® autoinjector (40 mg/0.8 mL) and a single-dose prefilled glass syringe (20 mg/0.4 mL, 40 mg/0.8 mL). It has received FDA approval for 7 of the 9 inflammatory conditions for which Humira is approved Amjevita is not indicated for hidradenitis suppurativa or uveitis. Although approved for adults with ulcerative colitis (UC), Amjevita is not indicated for pediatric UC.

COVID-19: NOTABLE DEVELOPMENTS

Data from the CDC’s Vaccine Safety Datalink (VSD) surveillance system identified a preliminary safety concern for ischemic stroke in those ≥ 65 years old who received the Pfizer/Biontech bivalent COVID-19 vaccine. Other surveillance systems and subsequent evaluation have not replicated the safety concern. FDA’s VRBPAC convened in January 2023 to discuss future vaccine regimens for COVID-19, including the composition of primary and booster doses. The panel also discussed plans for an annual COVID-19 booster. The agency is continuing to monitor the XBB.1.5 subvariant of Omicron as it continues to increase across the US. The EUA for tixagevimab co-packaged with cilgavimab (Evusheld™) has been revised to limit its use for preexposure prophylaxis of COVID-19 when the majority of circulating variants are not expected to be susceptible to the agent; as a result, Evusheld is no longer authorized for use. The CDC has published an MMWR on safety monitoring of bivalent COVID-19 mRNA vaccine booster doses in children 5 to 11 years old; preliminary data demonstrates similar safety with the bivalent booster as observed with the monovalent booster. The ICER has published an updated assessment on value-based pricing of ritonavir-boosted nirmatrelvir (Paxlovid™) as an outpatient treatment for COVID-19, providing an update of the initial May 2022 analysis. Please refer to the COVID-19 disclaimer at the end of the publication.

2 | FEBRUARY 2023

DRUG INFORMATION HAPPENINGS & HIGHLIGHTS

• The CDC is reporting seasonal influenza-like illness (ILI) activity continues to decline across the country for the week ending January 21, 2023. The majority of influenza viruses detected are A(H3N2) and a lesser amount of A(H1N1). The FDA and ASHP are reporting shortages of oseltamivir phosphate (Tamiflu ®) by some generic manufacturers. Additionally, the FDA is reporting a shortage of zanamivir inhalation powder (Relenza®).

• The shared system REMS for mifepristone (Mifeprex®) has been modified to remove the requirement that mifepristone be dispensed only in certain healthcare settings (clinics, medical offices, and hospitals), and instead add certification of pharmacies that dispense the drug. Prior to the January 2023 update, the REMS program required certified prescribers to dispense mifepristone directly to the patient in a clinic, medical office, or hospital. REMS program information in the prescribing information was updated to state that mifepristone must only be dispensed by or under the supervision of a certified prescriber, or by certified pharmacies on prescriptions issued by certified prescribers. Mifepristone is an oral tablet indicated, in a regimen with misoprostol, for the medical termination of intrauterine pregnancy through 70 days gestation.

• Lupin has initiated a voluntary recall of 4 lots of quinapril 20 mg and 40 mg tablets to the consumer level due to presence of N-nitroso-quinapril greater than the acceptable daily intake limit. The marketing of these tablets was discontinued in September 2022.

• Use of rucaparib (Rubraca®) in recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer patients who are in a complete or partial response to platinum-based chemotherapy as maintenance treatment has been restricted to those with a deleterious BRCA mutation (germline and/or somatic)-associated. Rucaparib’s prostate cancer indication remains unchanged.

• The FDA has reported AstraZeneca plans permanent discontinuation of moxetumomab pasudotox-tdfk (Lumoxiti®) for August 31, 2023. Removal is not related to safety or efficacy but due to low clinical use since approval in 2018.

• EMD Serono is discontinuing manufacture of somatropin injection (Saizen®) — a recombinant human growth hormone (GH) indicated for the treatment of children with growth failure due to GH deficiency and the treatment of adults with either adult onset or childhood onset GH deficiency.

DRUG INFORMATION HAPPENINGS

• The American Academy of Pediatrics (AAP) has published a clinical practice guideline for the Evaluation and Treatment of Children and Adolescents with Obesity.

• The American College of Physicians (ACP) has updated the living clinical guidelines on treatment of osteoporosis.

• The FDA has released the annual “New Drug Therapy Approvals” report detailing the 37 novel drugs approved in 2022.

• The ICER published the final evidence report on etranacogene dezaparvovec-drlb (Hemgenix®) for hemophilia B and updated the previous hemophilia A analysis on valoctocogene roxaparvovec (Roctavian® , investigational).

• The FDA is monitoring the supply of pediatric ibuprofen and acetaminophen due to increased demand caused by higher levels of respiratory illness and has issued guidance on compounding certain ibuprofen products.

• The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline on hepatitis C in CKD has been published, updating the 2018 guidance.

PIPELINE NEWS

UPCOMING PRESCRIPTION

tislelizumab

Beigene/Novartis

velmanase alfa

Chiesi

filgrastim (biosimilar to Amgen’s Neupogen®)

Lupin

mirikizumab

Eli Lilly

daprodustat

GlaxoSmithKline

sparsentan Travere

fezolinetant

Astellas

efanesoctocog alfa

Sanofi

omaveloxolone

Reata/Abbvie

Cytokinetics

• IV

• Programmed cell death 1 (PD-1) inhibitor

• IV

• Enzyme replacement

Esophageal squamous cell carcinoma (unresectable or metastatic, 2nd-line)

Jan–Jun 2023

• IV

• Colony stimulating factor Neutropenia/leukopenia

• IV, SC

• Interleukin-23 (IL-23) antagonist

• Oral

• Hypoxia-inducible factor (HIF) stabilizer

• Oral

• Angiotensin II receptor blocker (ARB)

• Oral

Ulcerative colitis (moderate to severe)

Anemia due to CKD (dialysis-dependent, dialysis-independent)

Immunoglobulin A nephropathy (Berger’s disease)

Menopause vasomotor symptoms

• IV

Hemophilia

• Oral

Friedreich’s ataxia

02/28/2023

02/28/2023

• Oral

• Cardiac muscle myosin activator 02/28/2023

4 | FEBRUARY 2023
DRUG/BIOSIMILAR USER FEE ACT (PDUFA/BsUFA) DATES
MANUFACTURER FORMULATION THERAPEUTIC CLASS PROPOSED CLINICAL USE ANTICIPATED FDA DECISION
DRUG NAME
Jan–Jun
Alpha-mannosidosis
2023
February
2023
Feb–Mar 2023
02/01/2023
02/17/2023
• Neurokinin-3 (NK3) receptor antagonist 02/22/2023
• Coagulation factor VIII (recombinant)/von Willebrand factor
A
• Nuclear factor erythroid 2–related factor 2 (Nrf2) pathway activator
omecamtiv mecarbil
Heart failure with reduced ejection fraction (HFrEF)

RECENT FDA APPROVALS

DRUG NAME MANUFACTURER

anacaulase-bcdb (Nexobrid®) Vericel

albuterol/budesonide (Airsupra™)

AstraZeneca

DESCRIPTION

New Drugs

• BLA approval 12/28/2022; Orphan Drug

• Indicated for eschar removal in adults with deep partial thickness and/or full thickness thermal burns

• Safety and effectiveness have not been established for the treatment of the following: chemical or electrical burns; burns on the face, perineum, or genitalia; burns on the feet of patients with diabetes or occlusive vascular disease; circumferential burns; patients with significant cardiopulmonary disease, including inhalation injury; it is not recommended for wounds contaminated with radioactive or other hazardous substances

• Botanical drug product containing proteolytic enzymes

• Topical gel: 8.8%

• Recommended dosage is 1.94 g of anacaulase-bcdb in 2 g powder mixed with 20 g gel per 1% body surface area (BSA), or 4.85 g of anacaulase-bcdb in 5 g powder mixed with 50 g gel per 2.5% BSA; may be applied in up to 2 applications of 4 hours each; first application may be applied to an area of up to 15% BSA, second application may be applied 24 hours later for a total treated area for both applications not exceeding 20% BSA; product is only to be administered by an HCP; topical use only

• 505(b)(2) NDA approval 01/10/2023; Standard Review

• Indicated for as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in patients with asthma ≥ 18 years of age

• Beta2-adrenergic agonist (albuterol) and corticosteroid (budesonide) combination

• Inhalation aerosol: pressurized metered-dose inhaler that delivers a fixed-dose combination of albuterol 90 mcg and budesonide 80 mcg per actuation

• Recommended dosage is 180 mcg/160 mcg (administered as 2 actuations of albuterol/budesonide 90 mcg/80 mcg) by oral inhalation as needed for asthma symptoms; maximum of 6 doses (12 inhalations) in a 24-hour period

RECENT FDA APPROVALS continued

DRUG NAME MANUFACTURER

risperidone (Rykindo®)

Shandong Luye

bexagliflozin (Brenzavvy™)

TheracosBio

DESCRIPTION

New Drugs continued

• 505(b)(2) NDA approval 01/13/2023; Standard Review

• Indicated for treatment of schizophrenia in adults, and as monotherapy or as adjunctive therapy to lithium or valproate for maintenance treatment of bipolar I disorder in adults

• Atypical antipsychotic

• Extended-release injectable suspension: 12.5 mg, 25 mg, 37.5 mg, 50 mg singledose kit

• Recommended dosage is 25 mg IM every 2 weeks, administered into the gluteal muscle by an HCP; patients not responding to 25 mg can have doses increased to 37.5 mg or 50 mg (maximum dose of 50 mg every 2 weeks); tolerability with oral risperidone must be established prior to use of the IM product, and patients should take the first dose of IM product along with 7 days of oral risperidone

• Boxed warning for increased mortality in elderly patients with dementia-related psychosis

• NDA approval 01/20/2023; Standard Review

• Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

• Not recommended in patients with type 1 diabetes mellitus as it may increase the risk of diabetic ketoacidosis in these patients

• Sodium-glucose co-transporter 2 (SGLT2) inhibitor

• Oral tablet: 20 mg

• Recommended dosage is 20 mg once daily in the morning, with or without food

505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.

COVID-19 Disclaimer: For the most current COVID-19 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.

Glossary:

ADR adverse reaction

ASHP American Society of Health-System Pharmacists

BLA Biologics License Application

BRCA BReast CAncer gene

CDC Centers for Disease Control and Prevention

CKD chronic kidney disease

COVID-19 Coronavirus Disease 2019

EUA Emergency Use Authorization

FDA Food and Drug Administration

HCP healthcare professional

References:

ICER Institute for Clinical and Economic Review

IM intramuscular

IV intravenous

MMWR Morbidity and Mortality Weekly Report

MRI magnetic resonance imaging

mRNA messenger ribonucleic acid

NDA New Drug Application

NIH National Institutes of Health

PET positron emission tomography

RCT randomized controlled trial

REMS Risk Evaluation and Mitigation Strategies

SC subcutaneous

SDV single-dose vial

SUVR standard uptake value ratio

TNF tumor necrosis factor

US United States

VRBPAC Vaccines and Related Biological Products Advisory Committee

WHO World Health Organization

aap.org cdc.gov acpjournals.org ajmc.com ashp.org fda.gov icer.org kidneyinternational.org
© 2023.
reserved.
Magellan Rx Management, a Prime Therapeutics LLC company. All rights
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