Clinical Alert November 2022

TRENDING TOPICS

NEW DRUG FOR LOU GEHRIG’S DISEASE

The US FDA has approved a novel fixed-dose combination of sodium phenylbutyrate and taurursodiol (Relyvrio™) for the treatment of adults with amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease). ALS is a rare, incurable disease that progressively attacks nerve cells responsible for voluntary movement, including swallowing and breathing. Patients typically die of respiratory failure within 5 years of symptom onset. Relyvrio, expected to be available in 4Q 2022, is a powder for oral suspension in single-dose packets containing 3 g of sodium phenylbutyrate and 1 g of taurursodiol. After dilution in 8 oz of room temperature water, the suspension is administered orally or via feeding tube once daily for 3 weeks, then twice daily. There are several drug and disease state interactions outlined in the label.

Efficacy and safety were evaluated in the phase 2, multicenter, randomized, double-blind, placebocontrolled CENTAUR trial that included 137 patients with a diagnosis of ALS and symptom onset in the previous 18 months. At 24 weeks, the ALS Functional Rating Scale-Revised (ALSFRS-R) total score decreased by 1.24 points per month with Relyvrio compared to 1.66 points per month in the placebo group (difference, 0.42 points per month; 95% CI, 0.03 to 0.81; p=0.03). In an openlabel extension in which all patients were administered Relyvrio for up to 30 months, the risk of death was 44% lower (HR, 0.56; 95% CI, 0.34 to 0.92; p=0.023) in participants originally randomized to Relyvrio; median survival duration was 25 months in the Relyvrio group and 18.5 months for those who originally received placebo.

In September 2022, ICER released a final evidence report assessing Relyvrio and edaravone (Radicava ORS®) added to standard care for the treatment of ALS. Relative to standard care alone, Relyvrio was deemed comparable or better; edaravone was rated comparable or incremental for the limited population studied, but there was insufficient evidence to draw conclusions about efficacy in a broader population.

BIOSIMILAR CORNER: VEGZELMA®

The fourth biosimilar to bevacizumab (Avastin®) has received FDA approval for the treatment of 6 types of cancer. Bevacizumab-adcd (Vegzelma) is a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of select patients with metastatic colorectal cancer; unresectable, locally advanced, recurrent, or metastatic non-squamous NSCLC; recurrent glioblastoma; metastatic renal cell carcinoma; persistent, recurrent, or metastatic cervical cancer; and epithelial ovarian, fallopian tube, or primary peritoneal cancer. Vegzelma shares all of Avastin’s indications, with the exception of adjuvant treatment of hepatocellular carcinoma. Both products carry a limitation of use stating that the drug is not approved for the adjuvant treatment of colon cancer. Like Avastin, Vegzelma is approved as 100 mg/4 mL and 400 mg/16 mL SDVs. Dosing of the IV infusion is weight based, and frequency is based on cancer type. Product launch is expected in the first half of 2023.

COVID-19: NOTABLE DEVELOPMENTS

The FDA has amended the EUAs for the Moderna and Pfizer-Biontech bivalent COVID-19 vaccines to authorize use as a single booster dose in children as young as 6 years and 5 years of age, respectively, and the CDC has expanded its recommendations on the bivalent vaccines to include children 5 to 11 years of age. The FDA updated Evusheld™ (tixagevimab co-packaged with cilgavimab) Fact Sheets to inform of the risk of COVID-19 due to certain variants that are not neutralized by Evusheld pre-exposure prophylaxis. The Fact Sheet for Healthcare Providers catalogs variants with reduced susceptibility to Evusheld components, including Omicron variants. The CDC published an MMWR discussing the effectiveness of a second COVID-19 booster dose against infection, hospitalization, or death among nursing home residents between March 29, 2022 and July 25, 2022, when Omicron subvariants BA.2, BA.4, and BA.5 were predominant. Please refer to the COVID-19 disclaimer at the end of the publication.

DRUG INFORMATION HAPPENINGS & HIGHLIGHTS

• Dupilumab (Dupixent®) was granted a new indication for the treatment of adults with prurigo nodularis. Dupilumab is the first drug to be approved for this rare skin condition. The recommended dosage is an initial dose of 600 mg (two 300 mg SC injections), followed by 300 mg every other week.

• Golden State Medical Supply has issued a voluntary recall of atenolol 25 mg tablets and clopidogrel 75 mg tablets. Both products share the lot number GS046745, and it was discovered that clopidogrel 75 mg tablets had been labeled as atenolol 25 mg tablets.

• The FDA has approved Boostrix (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed [Tdap]) for immunization during the third trimester of pregnancy to prevent pertussis, also known as whooping cough, in infants < 2 months of age. Boostrix is also indicated as an active booster immunization against tetanus, diphtheria, and pertussis in individuals ≥ 10 years of age.

• The FDA has granted Accelerated Approval to selpercatinib (Retevmo®) for adults with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or that have no satisfactory alternative treatment option. The FDA also granted regular approval for adults with locally advanced or metastatic NSCLC with a RET gene fusion, as detected by an FDA-approved test; the prior Accelerated Approval occurred in 2020.

• The labeling for Evekeo ODT® (amphetamine sulfate) has been revised to change the indication for the treatment of ADHD in pediatric patients to include only patients 6 to 17 years of age; the indication previously covered patients 3 to 17 years of age. The 2.5 mg strength was previously indicated as a starting dose in patients 3 to 5 years old. All information related to the 2.5 mg strength has been removed from the label. The 5 mg, 10 mg, 15 mg, and 20 mg orally disintegrating tablets (ODTs) remain available.

DRUG INFORMATION HAPPENINGS

• The FDA has released information on a shortage of immediate-release amphetamine mixed salts (Adderall®).

• The American College of Rheumatology (ACR) released a Guideline Summary outlining updates that will be published in the full manuscript of the 2022 ACR Guideline for the Prevention and Treatment of GlucocorticoidInduced Osteoporosis.

• The American Society of Clinical Oncology (ASCO) issued a Guideline Rapid Recommendation Update in response to safety signals and efficacy improvements associated with poly(ADP-ribose) polymerase (PARP) inhibitors in various settings in the management of ovarian cancer.

• The CDC issued guidance for the use of tecovirimat (Tpoxx®) under the expanded access investigational new drug protocol for the 2022 monkeypox outbreak. Additionally, the CDC published an MMWR describing the usage and reported adverse events of tecovirimat in the treatment of monkeypox.

• The CDC published an MMWR discussing the incidence of monkeypox among unvaccinated persons compared with those receiving ≥ 1 dose of the Jynneos® (Smallpox and Monkeypox Vaccine, Live, Non-replicating). Early data suggest that a single dose of the vaccine provides some protection; however, the full two-dose series is recommended.

PIPELINE NEWS

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

microbiota suspension Ferring

teplizumab Provention Bio

etranacogene dezaparvovec CSL Behring

poziotinib Spectrum

mirvetuximab soravtansine Immunogen

• Rectal

• Microbiome therapy

• IV

• Anti-cluster of differentiation 3 (CD3) antibody

• IV

• Gene therapy

• Oral

• Receptor tyrosine kinase inhibitor

• IV

• Anti-folate receptor alpha (FRα) antibody and cytotoxic agent conjugate

Clostridioides difficile infection (recurrent)

Type 1 diabetes mellitus (delay/prevention)

November 2022

11/17/2022

Hemophilia B 11/24/2022

Non-small cell lung cancer (human epidermal growth factor receptor 2 [HER2] exon 20 insertion mutations)

Ovarian cancer (FRα-high platinum-resistant, 1 to 3 prior systemic treatments)

11/24/2022

11/28/2022

RECENT FDA APPROVALS

NAME MANUFACTURER DESCRIPTION

New Drugs

futibatinib (Lytgobi®) Taiho Oncology

• NDA approval 09/30/2022; Accelerated Approval, Assessment Aid, Breakthrough Therapy, Orphan Drug, Priority Review, Real-Time Oncology Review

• Indicated for the treatment of adults with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor (FGFR) 2 gene fusions or other rearrangements; continued approval for this use may require demonstration of benefit in confirmatory clinical trials

• FGFR kinase inhibitor

• Oral tablet: 4 mg

• Recommended dosage is five 4 mg tablets (20 mg) once daily, with or without food, at approximately the same time each day, until disease progression or unacceptable toxicity

furosemide (Furoscix®) scPharmaceuticals

• 505(b)(2) NDA approval 10/07/2022; Standard Review

• Indicated for the treatment of congestion due to fluid overload in adults with NYHA Class II/III chronic heart failure

• Not indicated for emergency situations or in patients with acute pulmonary edema

• Loop diuretic

• Injection: 80 mg/10 mL single-dose prefilled cartridge co-packaged with a single-use on-body infusor (which will deliver only an 80-mg dose)

• Recommended dosage is SC administration with the on-body infusor that is preprogramed to deliver 30 mg over the first hour, then 12.5 mg per hour for the subsequent 4 hours; it is not designed for chronic use and should be replaced with oral diuretics as soon as feasible

• Product availability is expected in 1Q 2023

RECENT FDA APPROVALS continued

DRUG

tremelimumab-actl (Imjudo®) AstraZeneca

teclistamab-cqyv (Tecvayli™) Janssen

DESCRIPTION

New Drugs continued

• BLA approval 10/21/2022; Assessment Aid, Orphan Drug

• Indicated in combination with durvalumab, for the treatment of adults with unresectable hepatocellular carcinoma (uHCC)

• Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blocking antibody

• Injection: 20 mg/mL of solution in 1.25 mL and 15 mL SDVs

• Recommended dosage in patients weighing ≥ 30 kg is 300 mg and in those weighing < 30 kg is 4 mg/kg; administered by an HCP as an IV infusion over 60 minutes, and and the patient should be observed for 60 minutes following completion of the tremelimumab-actl infusion; durvalumab is administered on cycle 1/day 1 after the tremelimumab-actl dose, then as durvalumab monotherapy every 4 weeks until disease progression or unacceptable toxicity

• BLA approval 10/25/2022; 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

• Injection: 30 mg/3 mL and 153 mg/1.7 mL of solution in SDVs

• Recommended dosage is SC step-up doses of 0.06 mg/kg on day 1, 0.3 mg/kg on day 4, then 1.5 mg/kg on day 7 and once weekly thereafter until disease progression or unacceptable toxicity; doses are administered by an HCP with appropriate personnel and equipment to manage severe reactions; pretreatment is recommended with oral or IV dexamethasone, a histamine-1 receptor antagonist, and an antipyretic 1 to 3 hours prior to each step-up dose and as needed for subsequent doses

• Boxed warning for cytokine release syndrome and neurologic toxicity including immune effector cell-associated neurotoxicity syndrome; as a result, patients should be hospitalized for 48 hours after administration of all doses within the step-up dosing schedule

• Available only through a restricted program under a REMS

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 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.

ADHD attention deficit hyperactivity disorder

BLA Biologics License Application

CDC Centers for Disease Control and Prevention

CI confidence interval COVID-19 Coronavirus Disease 2019

EUA Emergency Use Authorization FDA Food and Drug Administration

g gram(s)

References:

HCP healthcare professional

HR hazard ratio

ICER Institute for Clinical and Economic Review

IV intravenous

MMWR Morbidity and Mortality Weekly Report

NDA New Drug Application

NIH National Institutes of Health

NSCLC non-small cell lung cancer

NYHA New York Heart Association

cdc.gov fda.gov icer.org nejm.org onlinelibrary.wiley

oz ounce(s)

Q quarter

REMS Risk Evaluation and Mitigation Strategy SC subcutaneous SDV single-dose vial US United States

WHO World Health Organization