Clinical Alert - February 2021

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FEBRUARY 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

BEHAVIORAL HEALTH CORNER

COVID-19 UPDATE

DRUG INFORMATION HAPPENINGS & HIGHLIGHTS

PIPELINE NEWS

RECENT FDA APPROVALS

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


TRENDING TOPICS BEHAVIORAL HEALTH CORNER: DRUG OVERDOSE DEATH INCREASES The Centers for Disease Control and Prevention (CDC) has issued an official health advisory on the increase in drug overdose fatalities in the United States (US) prior to and during the coronavirus disease 2019 (COVID-19) pandemic. The intent of this Health Alert Network (HAN) advisory is to ensure that various stakeholders (e.g., healthcare professionals [HCPs], public health departments, first responders) are aware of the significant rise in drug overdose deaths. The increase is predominantly due to overdose deaths associated with synthetic opioids, such as illicitly made fentanyl. Additionally, there has been an increased rate of drug overdose deaths between March 2020 and May 2020 that corresponded with the initiation of public health measures to mitigate spread of COVID-19. Provisional data from the CDC’s National Center for Health Statistics (NCHS) show that greater than 83,000 drug overdose deaths occurred during the 12-month period ending June 2020, representing a worsening of the drug overdose epidemic and the greatest number of overdose deaths recorded to date. This increase started in 2019 and continued into 2020 before the COVID-19 national emergency in March 2020; however, the growth intensified during the pandemic. The CDC recommends the following: 1) expand naloxone availability/use and overdose prevention education; 2) expand access to substance use disorder treatment; 3) early intervention for those with higher overdose risk; and 4) advanced detection of overdose outbreaks due to fentanyl, fentanyl analogues, or other drugs to aid in response efficacy. Some of the HCPs’ roles include prescribing naloxone for those at risk of overdose, providing US Food and Drug Administration (FDA)approved medications for opioid use disorder (e.g., methadone, buprenorphine), and providing stimulant use disorder treatment in the form of psychosocial therapies. 2 | FEBRUARY 2021

PRETERM BIRTH DRUG UPDATE – MAKENA® Amag Pharmaceuticals has submitted a response to the FDA’s Notice of Opportunity for a Hearing (NOOH) on their proposal for market withdrawal of hydroxyprogesterone caproate injection (Makena). The response includes data and information supporting market availability, including that it is the only FDA-approved option for women at risk for preterm birth and that study findings show efficacy in minority women. As the agency reviews the submission, hydroxyprogesterone caproate injection will continue to be approved and available.

COVID-19: NOTABLE DEVELOPMENTS The FDA has issued a statement regarding the dosing schedules of the 2 authorized COVID-19 vaccines. Data currently support the 2 doses for each authorized messenger ribonucleic acid (mRNA) vaccine at the specified intervals. The authorized interval between the first and second dose is 21 days for the PfizerBioNTech COVID-19 vaccine and 28 days for the Moderna COVID-19 vaccine. The FDA is aware of discussions on changes to the dosing schedule, number of doses, formulation substitution, and the dose per injection in an effort to vaccinate more individuals; however, the agency states that until data are available supporting alternative doses or dosing strategies, HCPs are strongly recommended to follow the authorized dosing schedules for both COVID-19 vaccines. For more resources on COVID-19, visit the Magellan Rx Coronavirus Update webpage. For the most current information, visit the FDA, the CDC, the National Institutes of Health (NIH), the NIH guidelines, and World Health Organization (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 • For the week ending January 23, 2021, the CDC is reporting that influenza activity in the US continues to be lower than usual for this time of year. One jurisdiction reported low influenza-like illness (ILI) and all other jurisdictions are reporting minimal ILI; however, these data could be impacted by COVID-19 and should be interpreted carefully. As of January 29th, no shortages are being reported for antivirals. • Octapharma, the manufacturer of immune globulin, subcutaneous (human)-hipp, 16.5% solution (Cutaquig®), has announced the FDA’s extension of the shelf life of the product. Previously 24 months, the shelf life has been extended to 36 months when stored at 2°C to 8°C (36°F to 46°F). This extension is due to impending immunoglobulin supply concerns and applies to all future lots, as well as 42 lots that have already been distributed. • Nostrum has expanded their previously issued November 2, 2020 recall to include 2 additional lots of metformin hydrochloride (HCl) extended-release tablets, USP 750 mg (generic equivalent to Glucophage®). The recall is to the consumer level and is due to nitrosamine impurities greater than the acceptable daily intake limit of 96 ng/day.

• Bristol-Myers Squibb (BMS), the manufacturer of the injectable cancer agent nivolumab (Opdivo®), has announced voluntary withdrawal of the indication for the treatment of patients with metastatic small cell lung cancer (SCLC) with progression after platinumbased chemotherapy and ≥ 1 other line of therapy. This indication was previously approved under Accelerated Approval in 2018 based on the phase 1/2 CheckMate-032 trial. Subsequently, confirmatory trials (CheckMate-451 and -331) failed to meet overall survival endpoints. As a result, nivolumab’s labeling has been updated accordingly throughout to remove information on SCLC. Nivolumab continues to be FDA-approved for a number of other malignancies. • Sunstar Americas has announced an expansion of the initial chlorhexidine gluconate oral rinse, USP 0.12% (Paroex®) recall from October 27, 2020. The recall is being expanded to include products with an expiration date from December 31, 2020 through September 30, 2022. The recall remains to the consumer level and is due to potential contamination with Burkholderia lata. The product is a prescription oral rinse indicated for the treatment of gingivitis.

DRUG INFORMATION HAPPENINGS • The American College of Cardiology (ACC)/American Heart Association (AHA) Joint Committee has published a guideline for the management of patients with valvular heart disease (VHD). • The ACC has released a 2021 update to their 2017 Expert Consensus Decision Pathway for Optimization of Heart Failure (HF) Treatment addressing important issues regarding HF with reduced ejection fraction. A summary of 16 key points is available. • The FDA has released a report on the agency’s COVID-19 Pandemic Recovery and Preparedness Plan Initiative. • The US Preventive Services Task Force (USPSTF) has issued recommendations on screening for hepatitis B virus (HBV) infection in adolescents and adults. It is recommended to screen for HBV infection in adolescents and adults who are at an increased risk for infection (Grade: B).


PIPELINE

NEWS

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

FORMULATION THERAPEUTIC CLASS

PROPOSED CLINICAL USE

ANTICIPATED FDA APPROVAL

evinacumab Regeneron

• IV • Anti-angiopoietin-like protein 3 (ANGPTL3) antibody

Homozygous familial hypercholesterolemia

02/11/2021

trilaciclib G1 Therapeutic/Boehringer Ingelheim

• IV • Cyclin-dependent kinase (CDK) 4/6 dual inhibitor

SCLC

02/15/2021

umbralisib TG Therapeutics

• Oral • Phosphoinositide 3-kinase (PI3K) inhibitor

Marginal zone lymphoma (≥ 1 prior anti-CD20 based regimen)

02/15/2021

casimersen Sarepta

• IV • Antisense oligonucleotide

Duchenne muscular dystrophy (amenable to exon 45 skipping)

02/25/2021

cemiplimab-rwlc (Libtayo®) Regeneron

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

NSCLC (1st-line, ≥ 50% PD-L1 expression)

02/26/2021

melflufen Oncopeptides

• IV • Alkylating agent

Multiple myeloma

02/26/2021

udenafil Allergan

• Oral • Phosphodiesterase-5 (PDE5) inhibitor

Single ventricle heart disease (ages ≥ 12 years)

02/26/2021

valsartan/sacubitril (Entresto®) Novartis

• Oral • Angiotensin II receptor blocker/ neprilysin inhibitor

Heart failure with preserved ejection fraction (HFpEF)

02/26/2021

paclitaxel/encequidar Athenex

• Oral • Mitotic inhibitor/P-glycoprotein pump inhibitor

Breast cancer

02/28/2021

IV = intravenous

4 | FEBRUARY 2021


RECENT FDA

APPROVALS DRUG NAME MANUFACTURER

DESCRIPTION

New Drugs vericiguat (Verquvo®) Merck

• NDA approval 01/19/2021; Priority Review • Indicated to reduce the risk for cardiovascular death and HF hospitalization following a hospitalization for HF or need for outpatient IV diuretics in adults with symptomatic chronic HF and ejection fraction (EF) < 45% • Soluble guanylate cyclase (sGC) stimulator • Tablets: 2.5 mg, 5 mg, and 10 mg • Recommended starting dosage is 2.5 mg orally once daily with food; double the dose approximately every 2 weeks to achieve the target maintenance dose of 10 mg once daily, as tolerated • Boxed warning regarding embryo-fetal toxicity • Product availability is expected in February 2021

cabotegravir (Vocabria) Viiv

• NDA approval 01/21/2021; Fast Track; Priority Review • Indicated in combination with rilpivirine (Edurant®), for short-term treatment of human immunodeficiency virus 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a stable antiretroviral (ARV) regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine, for use as: » an oral lead-in to evaluate tolerability of cabotegravir prior to initiation of cabotegravir/rilpivirine ER injection (Cabenuva) » an oral therapy for patients who will miss planned injection dosing of cabotegravir/ rilpivirine ER injection • HIV-1 integrase strand transfer inhibitor (INSTI) • Tablet: 30 mg • Recommended dosage is 30 mg orally once daily for approximately 1 month (≥ 28 days) taken in combination with 25 mg rilpivirine orally once daily at about the same time each day with a meal

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 cabotegravir ER and rilpivirine ER (Cabenuva) Viiv

• NDA approval 01/21/2021; Fast Track; Priority Review • Indicated as a complete regimen for the treatment of HIV-1 infection in adults to replace a current ARV regimen in patients who are virologically suppressed (HIV-1 RNA < 50 copies/mL) on a stable ARV regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine • HIV-1 INSTI and HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) • Injection (co-packaged): » 400 mg/600 mg kit: cabotegravir ER (400 mg/2 mL) injectable suspension plus rilpivirine ER (600 mg/2 mL) injectable suspension » 600 mg/900 mg kit: cabotegravir ER (600 mg/3 mL) injectable suspension plus rilpivirine ER (900 mg/3 mL) injectable suspension • Recommended starting dose is 600 mg cabotegravir and 900 mg rilpivirine on the last day of oral lead-in; continuation injections should be initiated 1 month after initiation of injections at a dose of 400 mg cabotegravir and 600 mg rilpivirine monthly; each injection should be administered at a separate gluteal injection site, ≥ 2 cm apart • Before starting therapy with the long-acting injectable combination, oral administration of cabotegravir and rilpivirine should be given for approximately 1 month (lead-in) to evaluate the tolerability of each therapy

voclosporin (Lupkynis™) Aurinia

• NDA approval 01/22/2021; Fast Track; Priority Review • Indicated for use in combination with a background immunosuppressive therapy regimen for the treatment of adults with active lupus nephritis • Not recommended in combination with cyclophosphamide, as safety and efficacy of this combination have not been established • Calcineurin inhibitor • Capsule: 7.9 mg • Recommended starting dose is 23.7 mg orally twice daily swallowed whole on an empty stomach, in combination with mycophenolate mofetil and corticosteroids; adjust dose based on estimated glomerular filtration rate (eGFR); voclosporin should not be started if eGFR is ≤ 45 mL/min/1.73 m2 unless the benefit exceeds the risk; if therapeutic benefit has not been demonstrated by 24 weeks, consider discontinuation; safety and efficacy have not been established past 1 year • Boxed warnings for malignancies and serious infections

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.

References:

cdc.gov

6 | FEBRUARY 2021

fda.gov

hhs.gov

nih.gov © 2021, Magellan Health. All rights reserved.