Clinical Alert - December 2022

TRENDING TOPICS

FDA PANEL VOTES TO WITHDRAW MAKENA®

The FDA’s Obstetrics, Reproductive and Urologic Drugs Advisory Committee voted (14 to 1) for recommending that the FDA pursue withdrawal of hydroxyprogesterone caproate (Makena) from the US market. This marks the second time the panel voted against keeping the drug on the market; the first was in 2019. The injectable progestin, by Covis, was granted Accelerated Approved in 2011 to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. Approval was based on data that demonstrated that Makena improved the proportion of women who delivered at < 37 weeks of gestation (36.3% versus 54.9% for control); however, the risk of complications including miscarriage and stillbirth was numerically higher with Makena. Additionally, in 2020, the mandated confirmatory PROLONG trial failed to show a reduction in preterm delivery at < 35 weeks compared to placebo (11% versus 11.5%, respectively) or in neonatal mortality or morbidity (5.4% versus 5.2%, respectively). The final decision on withdrawal of Makena is at the discretion of the FDA.

CDC UPDATES GUIDELINES FOR OPIOID USE

The CDC updated their 2016 guidelines for outpatient prescribing of opioids for pain in adults with acute, subacute, and chronic pain, excluding pain related to sickle cell disease, active cancer, palliative care, and endof-life care. The agency provides 12 recommendations that focus on: 1) decision to initiate opioid therapy, 2) drug and dose selection, 3) initial therapy duration and follow up, and 4) risk/harm assessment. Key elements include maximizing nonpharmacologic and non-opioid therapies prior to considering opioids for acute pain. Non-opioid therapies are also preferred for subacute and chronic pain. Opioid therapy should be initiated with immediate-release agents at the lowest effective dose and duration appropriate for the type of pain. The benefits and risks should be assessed within 1 to 4 weeks of starting therapy for subacute or chronic pain or of dosage escalation and regularly as clinically appropriate.

MPOX: NOTABLE DEVELOPMENTS

The FDA launched a web-based application to request single-patient emergency Expanded Access for brincidofovir (Tembexa®). The oral orthopoxvirus nucleotide analog DNA polymerase inhibitor by Chimerix is approved to treat smallpox, based on animal study data. Tembexa is considered an off-label therapeutic option for mpox (monkeypox) in humans who meet specific eligibility criteria. The CDC issued an MMWR regarding severe mpox in hospitalized patients in the US from August to October 2022. The CDC advises considering early treatment of mpox with available therapeutics for people at risk for severe mpox disease, particularly in those with AIDS. The CDC published an MMWR reporting that, from May 17 to September 24, 2022, mpox rarely (0.3% of cases) occurred in children and adolescents in the US. In younger children, transmission was typically via skin-to-skin contact with a household member, and in adolescents, exposure was often through male-to-male sexual contact. The CDC advises increased mpox vaccination efforts and education on prevention strategies and sexual health.

COVID-19: NOTABLE DEVELOPMENTS

The FDA issued an EUA for anakinra (Kineret®) for treating COVID-19 in certain hospitalized adults with pneumonia requiring supplemental oxygen who are at risk for progression. Bebtelovimab is no longer authorized in the US because it is not expected to neutralize Omicron subvariants BQ.1 and BQ.1.1. The FDA granted an EUA for the Novavax COVID-19 vaccine, adjuvanted as a first booster dose (0.5 mL) given ≥ 6 months after the completion of primary vaccination with an authorized or approved COVID-19 vaccine in certain adults. The CDC’s ACIP voted on recommendations to update the childhood and adult immunization schedules, including incorporation of COVID-19 vaccines into the guidelines in early 2023. Please refer to the COVID-19 disclaimer at the end of the publication.

HAPPENINGS & HIGHLIGHTS

• The CDC is reporting seasonal influenza-like illness (ILI) is elevated throughout the US for the week ending November 19, 2022. Eighteen jurisdictions are reporting very high ILI activity, 17 are reporting high activity, 8 are reporting moderate activity, and 6 are reporting low activity. The FDA and ASHP are reporting shortages of oseltamivir by some generic manufacturers.

• Mylan Institutional is voluntarily recalling 1 lot of octreotide acetate injection 500 mcg/mL, packaged in cartons of ten 1 mL syringes. The recall is to the user (hospital/pharmacy) level and follows a product complaint of glass particles in a syringe.

• The FDA and ASHP are reporting shortages of amoxicillin capsules, chewable tablets, tablets, and oral suspension due to an increase in demand. Supply may be limited or available on allocation. Depending on the manufacturer and information source, release of supply may occur through early 2023. A guidance has been released for compounding certain beta-lactams in shortage.

• Aurobindo issued a voluntary consumer-level recall for 2 lots of quinapril 20 mg/hydrochlorothiazide 12.5 mg tablets due to a nitrosamine drug substancerelated impurity of N-nitroso-quinapril above the proposed interim limit.

• The FDA approved a new 2 mg/3 mL (0.68 mg/mL) presentation of the semaglutide (Ozempic®) pen injector that delivers 0.25 mg or 0.5 mg per injection. Previously approved presentations included the following singlepatient-use pens: 2 mg/1.5 mL (1.34 mg/mL) that delivers 0.25 mg or 0.5 mg per injection, 4 mg/3 mL (1.34 mg/mL) that delivers 1 mg per injection, and 8 mg/3 mL (2.68 mg/mL) that delivers 2 mg per injection.

• The agency approved a new 125 mg capsule of pexidartinib (Turalio®) to accommodate a new dosage of 250 mg twice daily to be taken orally with a lowfat meal. The 200 mg capsules, used to complete a 400 mg twice daily dose on an empty stomach, are no longer approved.

DRUG INFORMATION HAPPENINGS

• The US Preventive Services Task Force (USPSTF) published final recommendations on screening for anxiety (ages 8 to 18 years) and depression/suicide risk (ages 12 to 18 years) in children and adolescents.

• The USPSTF issued final recommendations on hormone therapy for preventing chronic conditions in postmenopausal people. They recommend against the use of hormone therapy, either estrogen alone (Grade D; in persons who have had a hysterectomy) or a combination of estrogen and progestin (Grade D), to prevent chronic health problems in this population.

• The Institute for Clinical and Economic Review (ICER) published a final evidence report titled Medications for Obesity Management: Effectiveness and Value. The report states that semaglutide (Wegovy™) and liraglutide (Saxenda®) provide a net health benefit compared to lifestyle modification alone (B+ and B ratings, respectively), while phentermine/topiramate (Qsymia®) and bupropion/naltrexone (Contrave®) were given C++ and C+ ratings, respectively, when compared to lifestyle modification.

• The FDA has issued a Federal Register notice on a preliminary assessment that certain naloxone products (up to 4 mg nasal spray and up to 2 mg autoinjector for IM or SC use) may be able to be used over-the-counter.

• The FDA published a Federal Register notice announcing the implementation of the Advancing Real-World Evidence (RWE) program which aims to improve RWE approaches in labeling and indication approval and provides select sponsors the opportunity to discuss with agency staff the use of RWE in product development.

PIPELINE NEWS

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

DRUG NAME MANUFACTURER

adagrasib Mirati

trastuzumab (biosimilar to Genentech’s Herceptin®) Novartis

toripalimab Coherus

FORMULATION THERAPEUTIC CLASS PROPOSED CLINICAL USE ANTICIPATED FDA DECISION

• Oral

• Kirsten RAt Sarcoma virus (KRAS) inhibitor

• IV

• Anti-human epidermal growth factor receptor 2 (HER2) antibody

• IV

• Programmed cell death 1 (PD-1) inhibitor

NSCLC (KRAS G12C mutation, ≥ 1 prior systemic therapy)

12/14/2022

Breast cancer; Gastric/ gastroesophageal cancer 12/20/2022

Nasopharyngeal cancer (recurrent or metastatic, 1st-line in combination with chemotherapy, subsequent monotherapy)

12/23/2022

lenacapavir Gilead

ublituximab

TG Therapeutics

mosunetuzumab Genentech

palovarotene

Ipsen

• Oral, SC

• HIV capsid inhibitor

• IV

• Anti-cluster of differentiate (CD) 20 antibody

• IV

• Anti-CD20/anti-CD3 antibody

• Oral

• Retinoic acid receptor gamma (RARγ) agonist

HIV-1 infection (heavily treatment-experienced) 12/27/2022

Multiple sclerosis (relapsing) 12/28/2022

Follicular lymphoma (relapsing/remitting, ≥ 2 prior systemic therapies)

Fibrodysplasia ossificans progressiva (prevention of heterotopic ossification)

12/29/2022

12/29/2022

RECENT FDA APPROVALS

DRUG NAME MANUFACTURER

mirvetuximab soravtansine-gynx (Elahere™) ImmunoGen

teplizumab-mzwv (Tzield™) Provention Bio

DESCRIPTION

New Drugs

• BLA approval 11/14/2022; Accelerated Approval, Orphan Drug, Priority Review

• Indicated for the treatment of adults with folate receptor alpha (Frα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received 1 to 3 prior systemic therapy regimens; diagnosis should be made based on an FDA-approved test; continued approval for this use may require demonstration of benefit in confirmatory clinical trials

• Frα-directed antibody and microtubule inhibitor conjugate

• Injection: 100 mg/20 mL solution in an SDV

• Recommended dosage is 6 mg/kg (adjusted ideal body weight) administered by an HCP as an IV infusion every 3 weeks until disease progression or unacceptable toxicity; ophthalmic exams should be conducted prior to starting therapy, every other cycle for the first 8 cycles, and as clinically indicated; premedication with a corticosteroid, antihistamine, antipyretic, antiemetic, ophthalmic topical steroid, and lubricating eye drop is recommended

• Boxed warning for ocular toxicity

• BLA approval 11/17/2022; Breakthrough Therapy, Priority Review

• Indicated to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients ≥ 8 years of age who currently have stage 2 type 1 diabetes

• CD3-directed antibody

• Injection: 2 mg/2 mL solution in an SDV

• Recommended dosage is administered by an HCP as an IV infusion over a minimum of 30 minutes once daily for 14 consecutive days, based on BSA dosing (day 1: 65 mcg/m2, day 2: 125 mcg/m2, day 3: 250 mcg/m2, day 4: 500 mcg/m2, days 5 through 14: 1,030 mcg/m2); obtain a CBC and liver enzyme tests prior to starting therapy and administer all age-appropriate vaccinations before staring therapy; premedicate before the infusion for the first 5 days of dosing with an NSAID or acetaminophen, an antihistamine, and/or an antiemetic

RECENT FDA APPROVALS continued

DESCRIPTION

New Drugs continued

etranacogene dezaparvovec-drlb (Hemgenix®) CSL Behring

• BLA approval 11/22/2022; Breakthrough Therapy, Orphan Drug, Priority Review

• Indicated for the treatment of adults with hemophilia B (congenital factor IX deficiency) who currently use factor IX prophylaxis therapy; have current or historical life-threatening hemorrhage; or have repeated, serious spontaneous bleeding episode

• Adeno-associated virus vector-based gene therapy

• Suspension for injection: supplied in a kit containing 10 to 48 vials (kit provides a dosage unit based on patient’s body weight); for single-use IV infusion only

• Recommended dosage is 2 x 1013 genome copies per kilogram of body weight (or 2 mL/kg body weight) administered by an HCP as an IV infusion after dilution with 0.9% sodium chloride solution at a constant infusion rate of 500 mL/hour (8 mL/min); baseline testing (e.g., factor IV inhibitor presence, liver health evaluation) should be used to select patients and post-administration monitoring is required (e.g., liver enzyme testing, factor IX activity, alpha-fetoprotein level testing and abdominal ultrasound in patients with risk factors for hepatocellular carcinoma, human factor IX inhibitors in certain circumstances)

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.

Glossary:

ACIP Advisory Committee on Immunization Practices

AIDS acquired immune deficiency syndrome

ASHP American Society of Health-System Pharmacists

BLA Biologics License Application

BSA body surface area

CBC complete blood count

CDC Centers for Disease Control and Prevention

References:

COVID-19 Coronavirus Disease 2019

DNA deoxyribonucleic acid

EUA Emergency Use Authorization

FDA Food and Drug Administration

HCP healthcare professional HIV human immunodeficiency virus IM intramuscular

IV intravenous

MMWR Morbidity and Mortality Weekly Report

cdc.gov fda.gov icer.org nejm.org uspreventiveservicestaskforce.org

NDA New Drug Application

NIH National Institutes of Health

NSAID nonsteroidal anti-inflammatory drug

NSCLC non-small cell lung cancer

SC subcutaneous

SDV single-dose vial

US United States

WHO World Health Organization

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