MAY 2022
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 NOTABLES
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 CMS: FINAL COVERAGE OF ADUHELM™
BEHAVIORAL HEALTH CORNER: IGALMI™
The CMS has issued a final Medicare National Coverage Determination (NCD) memorandum providing coverage criteria for FDA-approved monoclonal antibodies (mAbs) directed against amyloid for treating Alzheimer’s disease (AD). The NCD is for use of these agents in patients with a clinical diagnosis of mild cognitive impairment (MCI) due to AD or mild AD dementia, both confirmed with the presence of amyloid beta pathology consistent with AD. The intent of the CMS NCD is to provide a predictable pathway that allows Medicare coverage for any anti-amyloid mAb that meets the finalized coverage criteria.
The FDA has approved a new formulation of dexmedetomidine (Igalmi), a film for sublingual or buccal use. The alpha2-adrenergic receptor agonist is indicated in adults for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder. Dosing is based on the agitation severity, and a reduced dosage is recommended for those with hepatic impairment or who are ≥ 65 years old. The film requires administration under the supervision of an HCP, and vital signs and alertness should be monitored following administration to prevent falls and syncope. If agitation continues after the first dose, up to 2 additional doses can be given ≥ 2 hours apart; safety and effectiveness have not been established beyond 24 hours from the first dose.
Anti-amyloid mAbs that are FDA-approved for AD based upon efficacy from a surrogate endpoint (e.g., amyloid reduction) and are considered likely to result in a clinical benefit may be covered in an RCT conducted under an investigational new drug application (IND). In contrast, anti-amyloid mAbs that are FDA-approved for AD based on efficacy from a direct measure of clinical benefit may be covered in CMS-approved prospective comparative studies; data from these studies may be collected in a registry. Additional criteria are detailed for CMS-approved studies (e.g., diverse population representative of the population with MCI due to AD or mild AD dementia, neurocognitive evaluation, multidisciplinary dementia team, optimal medical management). CMS-approved studies are also required to address certain questions (e.g., improvement of health outcomes). Coverage provided in this manner is termed Coverage with Evidence Development. Biogen’s aducanumab-avwa (Aduhelm) is an amyloid beta-directed antibody granted Accelerated Approval for the treatment of AD; the indication states treatment should be initiated in patients with MCI or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. The Accelerated Approval was based on the surrogate endpoint of reduction in amyloid beta plaques, and continued approval may require demonstration of benefit in confirmatory clinical trials. 2 | MAY 2022
COVID-19: NOTABLE DEVELOPMENTS The FDA’s VRBPAC discussed considerations for strain composition decisions for future SARS-CoV-2 vaccines as well as considerations for the use of additional COVID-19 vaccine booster doses. ACIP also met to discuss similar considerations. Sotrovimab is no longer authorized for treating COVID-19 in any US region due to increased levels of Omicron BA.2 subvariant cases. The NIH COVID-19 treatment guidelines have been updated with sotrovimab no longer recommended to treat COVID-19 due to substantially reduced in vitro activity against this subvariant that is dominant in the US. The CDC has published an MMWR; the data supports that in adults who received the Janssen vaccine as the primary COVID-19 series, preference should be for receipt of a heterologous mRNA vaccine booster dose ≥ 2 months later. An MMWR has shown that in persons with prior infection, receipt of a COVID-19 mRNA vaccination resulted in reduced hospitalization (vaccine effectiveness was 35% after dose 2, 68% after booster dose) during the Omicronpredominant period. Please refer to the COVID-19 disclaimer at the end of the publication.
DRUG INFORMATION
HAPPENINGS & HIGHLIGHTS • Adamis has announced a voluntary recall of 4 lots of Symjepi™ (epinephrine) injection 0.15 mg (NDC 78670-0131-02) and 0.3 mg (NDC 78670-0130-02) single-dose prefilled syringes. The recall is to the consumer level and is due to the potential for the needle to clog, preventing delivery of epinephrine. • The FDA has approved an extension of the expiration dating from 24 months to 36 months for the immune globulins Asceniv™ and Bivigam® when stored at 2°C to 8°C; the extension applies to all existing product lots currently in the supply chain and to future production in all vial sizes. • Pfizer has announced a voluntary recall to the consumer level of certain lots of Accuretic™ (quinapril HCl/hydrochlorothiazide) tablets and authorized generics by Greenstone. The recall is due to a nitrosamine impurity higher than the acceptable daily limit, N-nitroso-quinapril. • Sandoz has voluntarily recalled 13 lots of Orphenadrine Citrate 100 mg ER tablets to the consumer level. The recall is due to a nitrosamine impurity above the acceptable daily limit.
• A new maintenance dosage of semaglutide (Ozempic®), 2 mg SC once weekly, has been approved. Previously, the maximum recommended dosage was 1 mg once weekly. Along with the new dosage regimen, a new strength, 8 mg/3 mL (2.68 mg/mL) in a new singlepatient-use pen that delivers 2 mg per injection will be available. • The FDA has approved a partial prescription to OTC switch for Perrigo’s mometasone furoate monohydrate 50 mcg (Nasonex® 24HR Allergy). OTC use of the product is for temporary relief of symptoms of hay fever or other upper respiratory allergies (nasal congestion, sneezing, runny nose, itchy nose) in ages ≥ 2 years old. Product availability is expected later in 2022. • Mylan issued a voluntary recall of 1 batch of Insulin Glargine-yfgn Injection, 100 units/mL (U-100) (NDC 49502-0393-80, batch BF21002800), packaged in a 10 mL vial inside a carton due to the potential for the label to be missing on some vials. Notably, the recall is for the unbranded Insulin Glargine-yfgn vial (not the branded Semglee™ vial).
DRUG INFORMATION HAPPENINGS • The American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) has published 2022 guidelines for the management of heart failure. • The American College of Rheumatology (ACR) and American Association of Hip and Knee Surgeons (AAHKS) have released a guideline summary of updated recommendations for drug therapy in patients with rheumatic disease undergoing elective total hip arthroplasty or total knee arthroplasty. • The Institute for Clinical and Economic Review (ICER) has published a White Paper on Orphan Drugs. • The ICER has published an Evidence Report on the effectiveness and value of trilaciclib (Cosela™) and plinabulin (investigational) for the prevention of chemotherapy-induced neutropenia and other myelosuppressive effects.
PIPELINE
NEWS
UPCOMING PRESCRIPTION DRUG/BIOSIMILAR USER FEE ACT (PDUFA/BsUFA) DATES DRUG NAME MANUFACTURER
FORMULATION THERAPEUTIC CLASS
PROPOSED CLINICAL USE
ANTICIPATED FDA APPROVAL
faricimab-svoa (Vabysmo®) Genentech
• Intravitreal • Angiopoietin-2 inhibitor/ vascular endothelial growth factor (VEGF) inhibitor
Diabetic retinopathy
May 2022
edaravone Mitsubishi Tanabe
• Oral • Neuroprotective agent
Amyotrophic lateral sclerosis
05/12/2022
cantharidin Verrica
• Topical • Blistering agent
Molluscum contagiosum
05/24/2022
tapinarof Roivant
• Topical • Non-steroidal antiinflammatory drug
Plaque psoriasis (mild to severe)
05/26/2022
ipilimumab (Yervoy®) Bristol-Myers Squibb
• IV • Cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody
Esophageal squamous cell carcinoma (1st-line, with nivolumab)
05/27/2022
miglustat Amicus
• Oral • Cipaglucosidase alfa stabilizer
Pompe disease (in combination with cipaglucosidase alfa)
05/29/2022
tirzepatide Eli Lilly
• SC • GLP-1 receptor agonist/ glucose-dependent insulinotropic polypeptide (GIP) receptor agonist
Type 2 diabetes mellitus
05/30/2022
4 | MAY 2022
RECENT FDA
APPROVALS DRUG NAME MANUFACTURER
DESCRIPTION
New Drugs testosterone undecanoate (Tlando™) Antares
• 505(b)(2) NDA approval 03/28/2022; Standard Review • Indicated for testosterone replacement therapy in adult males for conditions
abacavir/dolutegravir/ lamivudine (Triumeq PD™) Viiv
• NDA approval 03/30/2022; Priority Review • Indicated for the treatment of HIV-1 infection in pediatric patients weighing
associated with a deficiency or absence of endogenous testosterone Safety and efficacy in males < 18 years old have not been established Androgen Oral capsule: 112.5 mg Recommended dosage is 225 mg twice daily with food; serum testosterone should be monitored after starting therapy to guide treatment; before starting therapy, confirm the diagnosis of hypogonadism by ensuring that serum testosterone levels have been assessed in the morning on ≥ 2 separate days and that these levels are below the normal range • Schedule III controlled substance • Boxed warning for blood pressure increases • Product availability is expected in 2Q 2022 • • • •
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≥ 10 kg Triumeq PD alone is not recommended in patients with resistance-associated integrase substitutions or clinically suspected INSTI resistance because the dose of dolutegravir is insufficient in these subpopulations Combination of 2 nucleoside analogue reverse transcriptase inhibitors (abacavir, lamivudine) and an INSTI (dolutegravir) Tablet for oral suspension: 60 mg abacavir/5 mg dolutegravir/30 mg lamivudine; Triumeq PD tablets for oral suspension should not be interchanged with Triumeq tablets on a mg-per-mg basis due to differences in the PK profiles of the dolutegravir component Recommended dosage in pediatric patients is based on the patient’s body weight: 10 kg to < 14 kg: 4 tablets once daily; 14 kg to < 20 kg: 5 tablets once daily; 20 kg to < 25 kg: 6 tablets once daily; fully disperse the tablets in 20 mL of drinking water in the supplied cup by swirling until no lumps remain; administer within 30 minutes of mixing with or without food; Triumeq PD is recommended in pediatric patients weighing 10 kg to < 25 kg and should not be used in adults; it may lead to suboptimal dosing for patients weighing ≥ 25 kg Boxed warnings for hypersensitivity reactions and exacerbations of hepatitis B
RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER
DESCRIPTION
New Drugs continued alpelisib (Vijoice®) Novartis
• NDA approval 04/05/2022; Accelerated Approval, Assessment Aid, Orphan Drug, Priority Review, Real-Time Oncology Review • Indicated for the treatment of adult and pediatric patients ≥ 2 years old with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy; continued approval may require demonstration of benefit in confirmatory clinical trials • Kinase inhibitor • Oral tablet: 50 mg, 125 mg, 200 mg; alpelisib is also available as tablets from Novartis under the trade name Piqray® • Recommended dosage is 50 mg once daily with food in pediatric patients and 250 mg once daily with food in adults
bevacizumab-maly (Alymsys®) Amneal
• BLA approval 04/13/2022; Standard Review; biosimilar to bevacizumab (Avastin®) • Indicated for the treatment of: » Metastatic colorectal cancer (mCRC), in combination with IV fluorouracil-based chemotherapy for 1st- or 2nd-line treatment » mCRC, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidineoxaliplatin-based chemotherapy for 2nd-line treatment in patients who have progressed on a 1st-line bevacizumab product-containing regimen » Unresectable, locally advanced, recurrent or metastatic non-squamous nonsmall cell lung cancer, in combination with carboplatin and paclitaxel for 1stline treatment » Recurrent glioblastoma in adults » Metastatic renal cell carcinoma in combination with interferon alfa » Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin, or paclitaxel and topotecan » Epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinumresistant recurrent disease in patients who received no more than 2 prior chemotherapy regimens • It is not indicated for the adjuvant treatment of colon cancer • VEGF inhibitor • Solution for injection: 100 mg/4 mL and 400 mg/16 mL in SDVs • Recommended dosage is weight- and indication-based administered as an IV infusion
505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.
6 | MAY 2022
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
HIV-1 human immunodeficiency virus type 1
PK pharmacokinetic
BLA Biologics License Application
INSTI integrase strand transfer inhibitor
Q quarter
IV intravenous
RCT randomized controlled trial
MMWR Morbidity and Mortality Weekly Report
SARS-CoV-2 severe acute respiratory syndrome coronavirus 2
CDC Centers for Disease Control and Prevention CMS Centers for Medicare & Medicaid Services COVID-19 Coronavirus Disease 2019 ER extended release
mRNA messenger ribonucleic acid NDA New Drug Application NDC National Drug Code
FDA Food and Drug Administration
NIH National Institutes of Health
GLP-1 glucagon-like peptide-1
OTC over-the-counter
HCl hydrochloride
PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
HCP healthcare professional
References: cdc.gov
cms.gov
fda.gov
nih.gov
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SC subcutaneous SDV single-dose vial US United States VRBPAC Vaccines and Related Biological Products Advisory Committee WHO World Health Organization