September Clinical Alert 2023

SEPTEMBER 2023

C LINICAL

ALERT

Your Monthly Source for Drug Information Highlights

EDITORIAL STAFF

EDITOR-IN-CHIEF

Maryam Tabatabai

PharmD

INTERIM EXECUTIVE EDITOR

Olivia Pane

PharmD, CDCES

DEPUTY EDITORS

Jessica Czechowski

PharmD

Carole Kerzic

RPh

Devon Trumbower

PharmD, BCPS

TRENDING TOPICS

BEHAVIORAL HEALTH UPDATES

WEIGHT MANAGEMENT CORNER

DRUG INFORMATION HAPPENINGS & HIGHLIGHTS

PIPELINE NEWS

RECENT FDA APPROVALS

TRENDING TOPICS

HOT TOPIC – BEYFORTUS™ APPROVED FOR RSV

The US FDA approved nirsevimab-alip (Beyfortus) by Sanofi to prevent respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in neonates and infants born during or entering their first RSV season and in children ≤ 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. Beyfortus is the second RSV fusion protein inhibitor monoclonal antibody to guard against RSV in infants and young children, following palivizumab (Synagis®), which was approved in 1998. Beyfortus provides 5 months of passive immunity with a single IM dose given prior to or during RSV season, compared to Synagis, which requires 5 monthly IM doses. In addition, Beyfortus is indicated for use in a broader pediatric population than Synagis; see product labels for details. In two placebo-controlled clinical trials, Beyfortus demonstrated vaccine efficacy (VE) of 70.1% and 74.9% against medically-attended RSV LRTI in healthy preterm (GA 29 to < 35 weeks) infants and later term infants (GA ≥ 35 weeks), respectively, who were going into or were in their first RSV season. A study that compared Beyfortus and Synagis included infants vulnerable to severe RSV disease (e.g., with chronic lung disease of prematurity or hemodynamically significant congenital heart disease) and reported similar VE with both agents when measured during the children’s first and second RSV seasons. Beyfortus will be available in a limited supply in early to mid-September, ahead of the 2023–2024 RSV season in the US.

The CDC, ACIP, and AAP recommend 1 dose of nirsevimabalip for all infants < 8 months of age born during or entering their first RSV season (50 mg for infants weighing < 5 kg and 100 mg for infants weighing ≥ 5 kg). In children between the ages of 8 and 19 months who remain at increased risk of severe RSV disease, a dose prior to their second RSV season is recommended (200 mg, administered as two 100 mg injections). AAP advises that if nirsevimab-alip is administered, palivizumab should not be given later that season. However, if palivizumab was administered initially for the season and < 5 doses were administered, then the infant should receive 1 dose of nirsevimab-alip and no further palivizumab should be administered. Children who received palivizumab in their first RSV season and continue to be at risk for severe RSV disease may receive nirsevimab-alip to cover their second RSV season.

BEHAVIORAL HEALTH UPDATES: NEW AGENTS

The US FDA approved the second neuroactive steroid GABA A receptor-positive modulator to treat postpartum depression (PPD) in adults. As the first oral agent indicated specifically for PPD, zuranolone (Zurzuvae™) will be available as 20 mg, 25 mg, and 30 mg capsules. The recommended dosage is 50 mg once daily in the evening for 14 days taken with a fatty meal. In the SKYLARK trial, Zurzuvae 50 mg resulted in a significant improvement in depressive symptoms as measured by HAMD-17 score on day 15 (difference from placebo, -4.0; p=0.0007). Zurzuvae may be used alone or as an adjunct to oral antidepressant therapy. The launch of Zurzuvae by Sage Therapeutics is pending controlled substance scheduling by the DEA.

Naloxone 3 mg nasal spray (Rivive™) by Harm Reduction Therapeutics has been approved for OTC use for the emergency treatment of known or suspected opioid overdose. Rivive is administered as 1 spray into 1 nostril; a call to 911 should immediately follow. A second dose may be given 2 to 3 minutes after the first dose if the person has not awakened. Availability of Rivive, packaged as 2 single-dose devices, is anticipated in early 2024.

WEIGHT MANAGEMENT CORNER

Novo Nordisk announced topline results from the phase 3 SELECT CV outcomes trial, which followed 17,604 adults who were overweight or obese, with established CVD and no prior history of diabetes mellitus, over 5 years. The study revealed that semaglutide (Wegovy®) 2.4 mg SC once weekly led to a statistically significant and superior reduction in MACE (defined as CV death, non-fatal MI, or non-fatal stroke) of 20% compared to placebo as an adjunct to standard care. Additionally, results were published from the phase 3 STEP HFpEF trial, which included 529 adults with symptomatic HFpEF and obesity. This study found that Wegovy 2.4 mg SC once weekly resulted in larger reductions in heart failure-related symptoms and greater weight loss compared to placebo over 52 weeks. The FDA approved a Wegovy 1.7 mg SC weekly dose as an additional maintenance dose for chronic weight management in overweight (with ≥ 1 weight-related comorbid condition) or obese adults.

DRUG INFORMATION HAPPENINGS & HIGHLIGHTS

• The FDA approved a single-use glass vial presentation for all available strengths of the diabetes medication tirzepatide (Mounjaro®). Strengths include 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg per 0.5 mL; previously, all strengths were approved as single-dose pens. The dosage of tirzepatide ranges from 2.5 mg to 15 mg SC once weekly.

• The agency is reporting that, due to an increase in demand, tirzepatide (Mounjaro) 7.5 mg/0.5 mL and 10 mg/0.5 mL single-use pens are on intermittent backorder through September 2023.

• Lupin Pharmaceuticals has announced that it is voluntarily recalling 2 lots of the oral contraceptive drospirenone/ ethinyl estradiol/levomefolate calcium (Tydemy™). This consumer-level action is due to low content of the inactive ingredient, ascorbic acid, which may impact the effectiveness of the product, leading to unexpected pregnancy. One lot also tested high for an impurity.

• The FDA changed pralsetinib (Gavreto®) from Accelerated Approval to regular approval for the treatment of adults with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test.

• Due to challenges associated with fulfilling the required confirmatory study, the FDA has removed the indication of pralsetinib (Gavreto) for the treatment of select patients with medullary thyroid cancer (MTC).

• A shortage is being reported for 60 mg and 70 mg capsules of Takeda’s CNS stimulant lisdexamfetamine dimesylate (Vyvanse®) due to a temporary delay at contract manufacturing sites. Recovery is expected in late September 2023. Supply of the remaining capsule strengths and the chewable tablets is available. Additionally, the FDA has approved several lisdexamfetamine dimesylate capsule and chewable tablet products from various manufacturers as first-time generics for Vyvanse. These generics carry indications for treatment of ADHD and binge eating disorder.

DRUG INFORMATION HAPPENINGS

• The CDC announced that they will launch the Bridge Access Program in the fall of 2023 to give free COVID-19 vaccine access to uninsured and underinsured adults.

• The DEA has issued a final rule allowing a one-time transfer of electronic prescriptions for initial filling of Schedule II through V controlled substances between retail pharmacies upon patient request.

• The CDC released an MMWR advising that, in clinical trials, both Abrysvo™ (Pfizer) and Arexvy (GlaxoSmithKline) RSV vaccines demonstrated moderate to high efficacy in preventing symptomatic RSV-associated LRTI in adults ≥ 60 years of age with a single dose (Abrysvo, VE of 88.9% in RSV season 1 and 78.6% in partial RSV season 2; Arexvy, VE of 82.6% in RSV season 1 and 56.1% in RSV season 2).

• The FDA and DEA provided an update to ongoing actions to resolve prescription stimulant shortages in the US. The agencies encourage manufacturers to meet allotted quota amounts, support the development of alternatives to treat ADHD, and encourage development of guidelines and diagnostic standards for ADHD.

• The USPSTF issued a final statement on screening children for lipid disorders. The task force determined that there is insufficient evidence to recommend for or against screening in patients < 20 years of age without signs and symptoms or known diagnosis of a cholesterol disorder.

• The USPSTF published a final Grade A statement recommending 0.4 mg to 0.8 mg of folic acid daily for anyone who is planning to or could become pregnant.

• The AHA and ACC published guidelines for diagnosis and management of chronic coronary disease (CCD).

PIPELINE NEWS

UPCOMING PRESCRIPTION

bimekizumab

UCB

cipaglucosidase alfa + miglustat

Amicus

• SC

• Interleukin (IL)-17 antagonist

• IV cipaglucosidase alfa + oral miglustat

• Acid alpha-glucosidase replacement therapy + glucosylceramide synthetase inhibitor

Plaque psoriasis

Pompe disease (late-onset)

DATES

September 2023

September 2023

lebrikizumab

Eli Lilly

nedosiran

Novo Nordisk

toripalimab

Coherus

• SC

• Interleukin (IL)-13 antagonist

• SC

• Small interfering RNA agent

• IV

• Programmed cell death 1 (PD-1) inhibitor

Atopic dermatitis (moderate to severe)

Hyperoxaluria

Nasopharyngeal cancer (advanced recurrent/metastatic, first-line with gemcitabine and cisplatin, subsequent monotherapy)

September 2023

September 2023

September 2023

motixafortide

BioLineRx

atezolizumab/ hyaluronidase

Genentech

momelotinib

GlaxoSmithKline

epinephrine

ARS

• IV

• C-X-C motif chemokine receptor 4 (CXCR4) antagonist

• SC

• Programmed cell deathligand 1 (PD-L1) inhibitor/ endoglycosidase

• Oral

• Janus kinase (JAK) inhibitor

• Intranasal

• Alpha/beta adrenergic agonist

Stem cell mobilization for autologous transplantation in patients with multiple myeloma

Hepatocellular carcinoma; Melanoma (BRAF-mutant); Nonsmall cell lung cancer; Small cell lung cancer; Soft tissue sarcoma

09/09/2023

09/15/2023

RECENT FDA APPROVALS

DRUG NAME MANUFACTURER

anthrax vaccine adsorbed, adjuvanted (Cyfendus™)

Emergent

quizartinib (Vanflyta®)

Daiichi Sankyo

DESCRIPTION

New Drugs

• BLA approval 07/20/2023; Standard Review

• Indicated for post-exposure prophylaxis of disease following suspected or confirmed exposure to Bacillus anthracis in persons 18 through 65 years of age when administered in conjunction with recommended antibacterial drugs; efficacy for this indication is based solely on animal models of inhalational anthrax

• Adjuvanted inactivated vaccine

• Suspension for IM injection: 100 mcg/mL

• Recommended dosage is two 0.5 mL doses administered IM 2 weeks apart

• The vaccine has been procured for use by the US government since 2019 as part of a pre-emergency use authorization package; the product will be transitioned to post-approval procurement

• NDA approval 07/20/2023; Assessment Aid, Fast Track, Orphan Drug, Priority Review

• Indicated for the treatment of adults with newly diagnosed AML that is FLT3 internal tandem duplication (ITD)-positive as detected by an FDA-approved test, in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy

• Quizartinib is not indicated as maintenance monotherapy following allogeneic HSCT

• Tyrosine kinase inhibitor antineoplastic

• Oral tablet: 17.7 mg, 26.5 mg

• Recommended dosage is 35.4 mg orally once daily for 2 weeks per cycle starting on day 8 of induction (for 7+3 regimen) and 35.4 mg orally once daily for 2 weeks per cycle starting on day 6 of consolidation. The maintenance dose is 26.5 mg orally once daily starting on day 1, with an increase to 53 mg once daily on day 15 of the first cycle if QTcF ≤ 450 ms. Treatment course consists of up to 2 cycles when used in combination with induction cytarabine and anthracycline, up to 4 cycles when used in combination with high-dose cytarabine consolidation, and up to 36 cycles when used as maintenance monotherapy, or until disease progression or unacceptable toxicity

• Labeled with a boxed warning related to QT prolongation, Torsades de Pointes, and cardiac arrest; requires dispensing through a REMS program

• Product is available

RECENT FDA APPROVALS continued

DRUG NAME MANUFACTURER

cantharidin (Ycanth™) Verrica

prothrombin complex concentrate, human-lans (Balfaxar®) Octapharma

avacincaptad pegol (Izervay™) Iveric Bio

talquetamab-tgvs (Talvey™)

Janssen Biotech

DESCRIPTION

• NDA approval 07/21/2023; Standard Review

• Indicated for the topical treatment of molluscum contagiosum in adult and pediatric patients ≥ 2 years of age; first FDA-approved treatment for this indication

• Keratolytic vesicant

• Topical solution: 0.7%

• Recommended dosage is a small droplet of solution applied and spread to cover the entire lesion by an HCP using the applicator provided, then removed with soap and water after 24 hours; application may be administered every 3 weeks as needed

• BLA approval 07/21/2023; Standard Review

• Indicated for the urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (e.g., warfarin) therapy in adults with need of an urgent surgery or invasive procedure

• Blood coagulation factor replacement

• Lyophilized powder for reconstitution: 500 IU range factor IX (FIX) in 20 mL; 1,000 IU range FIX in 40 mL SDVs

• Recommended dosage is individualized based on pre-treatment INR and patient body weight and is administered by an HCP as a single IV infusion concurrently with vitamin K; for pretreatment INR level of 2 to < 4, the dosage is 25 units of FIX/kg (maximum 2,500 units); for INR 4 to 6, the dosage is 35 units of FIX/kg (maximum 3,500 units); for INR > 6, the dosage is 50 units of FIX/kg (maximum 5,000 units)

• Labeling includes a boxed warning for arterial and venous thromboembolic complications

• NDA approval 08/04/2023; Priority Review

• Indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD)

• Complement inhibitor

• Intravitreal solution: 20 mg/mL SDV

• Recommended dosage is 2 mg (0.1 mL) administered by intravitreal injection by an HCP to each affected eye once monthly for up to 12 months

• BLA approval 08/09/2023; Accelerated Approval, Assessment Aid, Breakthrough Therapy, Orphan Drug, Priority Review

• Indicated for the treatment of adults with relapsed or refractory multiple myeloma who have received ≥ 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody; continued approval for this use may require demonstration of benefit in confirmatory clinical trials

• Bispecific GPRC5D-directed CD3 T-cell engager

• Solution for injection: 3 mg/1.5 mL, 40 mg/mL SDVs

• Recommended step-up dosing schedule is 0.01 mg/kg on day 1, 0.06 mg/kg on day 4, 0.4 mg/kg on day 7, and 0.8 mg/kg on day 10 (if continuing on a biweekly maintenance schedule) as an HCP-administered SC injection; maintenance dosing is 0.4 mg/kg once weekly starting on day 14 or 0.8 mg/kg every 2 weeks starting on day 24

• Labeling includes a boxed warning related to risks of CRS and neurologic toxicity, including ICANS; requires dispensing through a REMS program

RECENT FDA APPROVALS continued

DRUG NAME MANUFACTURER

elranatamab-bcmm (Elrexfio™) Pfizer

palovarotene (Sohonos™) Ipsen

DESCRIPTION

• BLA approval 08/14/2023; Accelerated Approval, Assessment Aid, Breakthrough Therapy, Orphan Drug, Priority Review, Project Orbis

• Indicated for the treatment of adults with relapsed or refractory multiple myeloma who have received ≥ 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody; continued approval for this use may require demonstration of benefit in confirmatory clinical trials

• Bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager

• Off-the-shelf solution for injection: 44 mg/1.1. mL, 76 mg/1.9 mL SDVs

• Recommended step-up dosing schedule of HCP-administered SC injections is 12 mg on day 1, 32 mg on day 4, and 76 mg on day 8 (all preceded by acetaminophen, dexamethasone, and diphenhydramine), followed by 76 mg weekly starting on day 15 and continuing through week 24, and then 76 mg every 2 weeks starting on week 25; labeling provides dosage modifications for adverse reactions

• Labeling includes a boxed warning related to risks of CRS and neurologic toxicity, including ICANS; requires dispensing through a REMS program

• Product availability is expected in the coming weeks

• NDA approval 08/16/2023; Breakthrough Therapy, Fast Track, Orphan Drug, Priority Review; Rare Pediatric Disease

• Indicated for reduction in the volume of new heterotopic ossification in adults and children ≥ 8 years of age for females and ≥ 10 years of age for males with fibrodysplasia ossificans progressiva (FOP)

• Retinoid

• Oral capsule: 1 mg, 1.5 mg, 2.5 mg, 5 mg, 10 mg

• For patients ≥ 14 years of age, the recommended maintenance dosage is 5 mg once daily, and the recommended flare-up dosage is 20 mg daily for 4 weeks followed by 10 mg daily for 8 weeks or until symptom resolution; for patients < 14 years of age, the recommended maintenance dose ranges from 2.5 mg to 5 mg based on weight, and the flare-up doses range from 5 mg to 20 mg based on weight and flare-up treatment phase; capsules should be administered orally with food at the same time each day

• Labeling includes a boxed warning for embryofetal toxicity and premature epiphyseal closure in growing pediatric patients

Glossary:

AAP American Academy of Pediatrics

ACC American College of Cardiologists

ACIP Advisory Committee on Immunization Practices

ADHD attention-deficit/hyperactivity disorder

AHA American Heart Association

AML acute myeloid leukemia

BLA Biologics License Application

BRAF V-Raf Murine Sarcoma Viral Oncogene

Homolog B

CD3 cluster of differentiation 3

CD38 cluster of differentiation 38

CDC Centers for Disease Control and Prevention

CNS central nervous system

COVID-19 Coronavirus Disease 2019

CRS cytokine release syndrome

CV cardiovascular

CVD cardiovascular disease

DEA Drug Enforcement Agency

FDA Food and Drug Administration

FLT3 feline McDonough sarcoma–like tyrosine kinase 3

GABA A gamma-aminobutyric acid type A

GPRC5D G protein-coupled receptor, class C, group 5, member D

HAMD-17 Hamilton Depression Rating Scale (17-point)

HF heart failure

HFpEF heart failure with preserved ejection fraction

ICANS immune effector cell-associated neurotoxicity syndrome

IM intramuscular

INR International Normalized Ratio

IU international units

IV intravenous

LRTI lower respiratory tract infection

MACE major adverse cardiovascular event

MI myocardial infarction

MMWR Morbidity and Mortality Weekly Report

NDA New Drug Application

OTC over-the-counter

QTcF absolute QT interval corrected for heart rate by Fridericia’s formula

REMS Risk Evaluation and Mitigation Strategy

RET RET proto-oncogene

RNA riboneucleic acid

RSV respiratory syncytial virus

SC subcutaneous

SDV single-dose vial

US United States

USPSTF US Preventive Services Task Force

VE vaccine efficacy

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.

Disclaimer: The content in this publication is not a substitute for professional medical advice. For questions regarding any medical condition or if you need medical advice, please contact your healthcare provider.

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