MRx Clinical Alert - February 2022

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

TRENDING TOPICS CMS PROPOSED COVERAGE OF ADUHELM™ The CMS has released a proposed draft National Coverage Determination (NCD) decision memorandum stating that Medicare coverage would be provided for FDAapproved monoclonal antibodies targeting amyloid for Alzheimer’s disease only for patients who are enrolled in a qualifying randomized, controlled clinical trial. Coverage provided in this manner is termed Coverage with Evidence Development (CED). This NCD would apply to Biogen’s amyloid beta-directed antibody aducanumab-avwa (Aduhelm), granted Accelerated Approval for the treatment of Alzheimer’s disease, initiated in patients with mild cognitive impairment (MCI) 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 than were studied. A recent brain MRI is required before starting therapy, and titration is required to the recommended maintenance dosage of 10 mg/kg administered as an IV infusion over approximately 1 hour every 4 weeks. Additional MRIs are required before the 7th and 12th infusions to monitor for amyloid-related imaging abnormalities-edema (ARIA-E) and ARIA-hemosiderin deposition (ARIA-H) which may require dose adjustments. CMS will make a final decision on the proposed NCD in April 2022. If the NCD is finalized, CMS will review clinical studies to determine if criteria from the NCD are met and will list CMS-approved clinical studies on the CMS coverage website. NIH-sponsored clinical studies would also be included in the proposed NCD. These trials are required to be conducted in a hospital-based outpatient setting.

BEHAVIORAL HEALTH CORNER: DENTAL ISSUES WITH BUPRENORPHINE The FDA has issued a Drug Safety Communication on dental issues (e.g., tooth decay, cavities, oral infections, and loss of teeth) with transmucosal buprenorphine formulations 2 | FEBRUARY 2022

dissolved in the mouth, following identification of 305 cases (121 serious cases). These problems have occurred both in patients with and without a history of prior dental issues. Based on these findings, buprenorphine tablets and films dissolved under the tongue or placed against the inside of the cheek will carry a new warning regarding these risks. Users of these products should be referred for dental care and have regular checkups. Buprenorphine is used for opioid use disorder (OUD) and pain; it is also available as a transdermal patch and injection, but these products do not currently carry dental concerns.

COVID-19: NOTABLE DEVELOPMENTS The FDA has granted approval to the Moderna COVID-19 vaccine (Spikevax™) for prevention of COVID-19 in those ≥ 18 years old; this vaccine has been available under EUA. The Agency has expanded the approved indication for the IV antiviral remdesivir (Veklury®) to include use in certain non-hospitalized adults and pediatric patients for the treatment of mild-to-moderate COVID-19 disease. The FDA has shortened the time between completion of a primary series with the Moderna COVID-19 vaccine and receipt of a booster dose to ≥ 5 months for individuals ≥ 18 years old. This aligns with the time interval after completion of the primary vaccine series with a PfizerBiontech COVID-19 vaccine and receipt of a booster for individuals ≥ 12 years old. The CDC also recommends that both mRNA boosters can be given ≥ 5 months following completion of the primary series. The US government has updated its official website providing locations of publicly available COVID-19 therapeutics (Evusheld™, molnupiravir, Paxlovid™). The White House is requiring insurance companies and health plans to cover 8 free OTC at-home COVID-19 tests per covered individual per month, and each residence in the US can order 4 free at-home COVID-19 tests. A meeting of the FDA’s VRBPAC will be held on February 15th to evaluate the EUA submission for use of the Pfizer-Biontech COVID-19 vaccine in children 6 months to 4 years old. Please refer to the COVID-19 disclaimer at the end of the publication.


HAPPENINGS & HIGHLIGHTS • For the week ending January 22, 2022, the CDC reported that influenza activity remained stable this week, while overall levels of respiratory illness decreased; activity varies by region. One jurisdiction reported very high influenza-like illness (ILI) activity, 11 high, 6 moderate, 10 low, 25 minimal, and 2 with insufficient data. As of December 7, 2021, no current shortages are being reported for antiviral medications. • Taro issued a voluntary recall of 1 lot of Clobetasol Propionate Ointment USP, 0.05% (NDC 51672-125903) packaged in 60 g tubes, to the consumer level (lot AC13786; expiration Dec. 2022) due to the presence of Ralstonia pickettii bacteria which was found by routine testing. This bacteria is present in the environment (soil, water) and is unlikely to lead to localized or systemic infections in healthy individuals, but an infection may occur in individuals who are immunocompromised or whose skin is not intact, leading to systemic infection. • Padagis has issued a voluntary recall to the consumer/ user level of 3 lots of Nitroglycerin Lingual Spray (NDC 45802-0210-02); the product is being recalled due to a complaint that the drug may not dispense from the spray bottle. This recall applies only to the 12 g spray bottle (not the 4.9 g spray bottle).

• The FDA has approved an Rx to OTC switch for alcaftadine (Lastacaft®). The product contains the same 0.25% alcaftadine strength and is now approved for OTC use in adults and children ≥ 2 years old. It is indicated for temporary relief of itchy eyes due to pollen, ragweed, grass, animal hair, and dander. The dosage is 1 drop in the affected eye(s) once daily. • Viona has voluntarily recalled 23 lots of Metformin HCl Extended-Release Tablets, USP 750 mg to the consumer level due to detection of an NDMA impurity, following an out-of-specification result observed for the product. • Secura Bio announced plans to withdraw panobinostat (Farydak®) from the US market. The drug received Accelerated Approval for use in combination with bortezomib and dexamethasone for patients with multiple myeloma who have received ≥ 2 prior regimens, including bortezomib and an immunomodulatory agent. Secura stated that the withdrawal is because it is not possible to complete the mandatory post-approval clinical studies to confirm clinical benefit. Additionally, Secura has also voluntarily withdrawn the indication (Accelerated Approval) of duvelisib (Copiktra®) for the treatment of patients with relapsed or refractory follicular lymphoma after ≥ 2 prior systemic therapies.

DRUG INFORMATION HAPPENINGS • The American Academy of Neurology (AAN) has published a practice guideline update on oral and topical therapies for the treatment of painful diabetic polyneuropathy. • The American Diabetes Association (ADA) has released their 2022 Standards of Medical Care in Diabetes; the 2022 version includes changes in the areas of diabetes screening, first-line therapy, pregnancy, and technology. • The American Heart Association (AHA) has published a scientific statement on comprehensive management of CV risk factors for adults with type 2 diabetes mellitus. • The living WHO guideline on drugs for COVID-19 has been updated.







sutimlimab Sanofi

• IV • Complement inhibitor

Cold agglutinin diseaserelated hemolysis


mitapivat Agios

• Oral • Pyruvate kinase activator

Pyruvate kinase deficiency


dextroamphetamine Hisamitsu

• Transdermal • CNS stimulant

Attention-deficit hyperactivity disorder


bardoxolone methyl Reata

• Oral • Nrf2 pathway activator

Alport syndrome-related chronic kidney disease


immune globulin (human) 10% Green Cross

• IV • Immunoglobulins (IgG)

Primary humoral immunodeficiency


ciltacabtagene autoleucel Janssen

• IV • Cellular immunotherapy/ CAR-T immunotherapy

Multiple myeloma (relapsed/ refractory)


episalvan Amryt

• Topical • Keratinocyte activator

Epidermolysis bullosa


lenacapavir Gilead

• Oral, SC • HIV capsid inhibitor

HIV-1 infection treatment (multidrug-resistant)


pacritinib CTI Biopharma

• Oral • Janus kinase (JAK) inhibitor



treprostinil DPI (Tyvaso® DPI) United Therapeutics

• Inhaled • Prostaglandin vasodilator

Pulmonary arterial hypertension; Idiopathic pulmonary fibrosis-associated pulmonary hypertension

Feb 2022

4 | FEBRUARY 2022




New Drugs levoketoconazole (Recorlev®) Strongbridge

• 505(b)(2) NDA approval 12/30/2021; Orphan Drug, Standard Review • Indicated for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative • Not approved for the treatment of fungal infections • Cortisol synthesis inhibitor • Oral tablet: 150 mg • Recommended dosage is 150 mg twice daily with or without food; titrate by 150 mg daily, no more frequently than every 2 to 3 weeks based on 24-hour urine-free cortisol levels and patient tolerability; dosage can be decreased to 150 mg once daily, if needed for tolerability; maximum recommended dosage is 1,200 mg daily, administered as 600 mg twice daily • Boxed Warnings for hepatotoxicity and QT prolongation • Product availability is expected in 1Q 2022

daridorexant (Quviviq™) Idorsia

• NDA approval 01/07/2022; Standard Review • Indicated for treatment of adults with insomnia characterized by difficulties with sleep onset and/or sleep maintenance • Orexin receptor antagonist • Oral tablet: 25 mg, 50 mg • Recommended dosage is 25 mg to 50 mg once per night taken 30 minutes before going to bed with ≥ 7 hours remaining prior to planned awakening; time to sleep onset may be delayed if taken with or soon after a meal; in moderate hepatic impairment, the maximum recommended dosage is 25 mg once per night • FDA has recommended designation as a controlled substance; schedule pending by the DEA • Product availability is expected in May 2022

olopatadine HCl and mometasone furoate (Ryaltris™) Glenmark

• 505(b)(2) NDA approval 01/13/2022; Priority Review • Indicated for the treatment of symptoms of seasonal allergic rhinitis in adult and pediatric patients ≥ 12 years old • Combination of histamine-1 (H1) receptor inhibitor and a corticosteroid • Nasal spray: 665 mcg olopatadine HCl and 25 mcg mometasone furoate per spray • Recommended dosage is 2 sprays in each nostril twice daily; should be primed before first use by releasing 6 sprays as well as when it has not been used for ≥ 14 days by releasing 2 sprays or releasing sprays until a fine mist is generated

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.



New Drugs continued abrocitinib (Cibinqo™) Pfizer

• NDA approval 01/14/2022; Priority Review • Indicated for the treatment of adults with refractory, moderate-to-severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable • Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants • JAK inhibitor • Oral tablet: 50 mg, 100 mg, 200 mg • Recommended dosage is 100 mg once daily » For those patients who are not responding to 100 mg once daily, recommended dosage is 200 mg once daily » For patients with moderate renal impairment or who are CYP2C19 poor metabolizers, recommended dosage is 50 mg once daily, or 100 mg once daily for those patients who are not responding to 50 mg once daily • Boxed Warnings for serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis • Product availability is expected in the coming weeks

daptomycin (Dapzura RT™) Baxter

• 505(b)(2) NDA approval 01/25/2022; Standard Review • Indicated for the treatment of: (1) complicated skin and skin structure infections (cSSSI) in adults and pediatric patients 1 to 17 years old, (2) Staphylococcus aureus bacteremia in adults including those with right-sided infective endocarditis, and (3) S. aureus bacteremia in pediatric patients 1 to 17 years old • Not indicated for treatment of pneumonia or left-sided infective endocarditis due to S. aureus, and not recommended for pediatric patients < 1 year old due to the risk of potential muscular, neuromuscular, and nervous system effects • Lipopeptide antibacterial • Injection: 500 mg lyophilized powder for reconstitution in an SDV • Recommended dosage depends on patient age, body weight, and indication; administered by slow IV push (over 2 minutes) in adults or IV infusion in adults and pediatric patients

tebentafusp-tebn (Kimmtrak®) Immunocore

• BLA approval 01/25/2022; Assessment Aid, Breakthrough Therapy, Orphan Drug, Priority Review, Project Orbis, Real-Time Oncology Review (RTOR) • Indicated for the treatment of HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma • Bispecific gp100 peptide-HLA-directed CD3 T cell engager • Injection: 100 mcg/0.5 mL solution in an SDV • Recommended dosage is 20 mcg via IV infusion over 15 to 20 minutes on day 1, 30 mcg IV on day 8, 68 mcg IV on day 15, and 68 mcg IV once every week thereafter • Boxed Warning for cytokine release syndrome

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.

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Glossary: CAR-T chimeric antigen receptor T cell CDC Centers for Disease Control and Prevention CMS Centers for Medicare & Medicaid Services

IV intravenous

Rx prescription

DEA Drug Enforcement Administration

MRI magnetic resonance imaging

SC subcutaneous

DPI dry powder for inhalation

mRNA messenger ribonucleic acid

SDV single-dose vial

NDC National Drug Code

US United States

NDMA N-nitrosodimethylamine

USP United States Pharmacopeia

NIH National Institutes of Health

VRBPAC Vaccines and Related Biological Products Advisory Committee

EUA Emergency Use Authorization FDA Food and Drug Administration

CNS central nervous system COVID-19 Coronavirus Disease 2019

HCl hydrochloride HIV human immunodeficiency virus HIV-1 human immunodeficiency virus 1

CV cardiovascular


CYP cytochrome P450

Nrf2 nuclear factor erythroid 2– related factor 2 OTC over-the-counter

WHO World Health Organization

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. 7 | FEBRUARY 2022

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