JUNE 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
COVID-19 NOTABLES
PIPELINE NEWS
RECENT FDA APPROVALS
DEPUTY EDITORS Jessica Czechowski PharmD Lara Frick PharmD, BCPS, BCPP Carole Kerzic RPh Leslie Pittman PharmD
DRUG INFORMATION HAPPENINGS & HIGHLIGHTS
TRENDING TOPICS NEW TYPE 2 DIABETES DRUG: MOUNJARO™
COVID-19: NOTABLE DEVELOPMENTS
A new injectable medication, tirzepatide (Mounjaro), has received approval as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). Tirzepatide is a novel agent that is an agonist at both the glucagon-like peptide-1 (GLP-1) receptor and glucose-dependent insulinotropic polypeptide (GIP) receptor. GLP-1 and GIP are natural incretin hormones involved in glycemic control, and activation of these hormones’ receptors reduces glucose levels, decreases food intake, and reduces body weight in patients with T2DM through enhancement of insulin secretion and reduction of glucagon.
The FDA has announced tentative upcoming VRBPAC meetings for the month of June. The meetings will be livestreamed and available via a webcast.
Tirzepatide is supplied as a single-dose pen in the strengths of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg for once-weekly SC injection. The starting dosage is 2.5 mg once weekly, increased to 5 mg after 4 weeks; if further glycemic control is required, the dose can be increased in 2.5 mg increments every 4 weeks to a maximum of 15 mg once weekly. Tirzepatide is not indicated for use in patients with type 1 diabetes mellitus and has not been studied in patients with a history of pancreatitis. Tirzepatide carries a boxed warning for the risk of thyroid c-cell tumors.
The Pfizer/Biontech COVID-19 vaccine EUA has been amended to authorize a single booster dose for children 5 to 11 years old ≥ 5 months following completion of the primary vaccine series. The FDA has limited the authorized use of the Janssen COVID-19 vaccine due to the risk for thrombosis with thrombocytopenia syndrome (TTS), a syndrome of rare and potentially life-threatening blood clots in combination with low levels of blood platelets that occurs within 1 to 2 weeks after vaccination. As a result, the authorized use of the Janssen COVID-19 vaccine has been limited to individuals ≥ 18 years old 1) for whom other authorized/approved COVID-19 vaccines are not accessible or clinically appropriate and 2) in those who otherwise would not receive a COVID-19 vaccine. Moderna has submitted an EUA for its COVID-19 vaccine for use in children 6 months to < 6 years of age as a 25 mcg two-dose primary series. The FDA has expanded the approval of the COVID-19 treatment remdesivir (Veklury®) to include certain pediatric patients ≥ 28 days of age weighing ≥ 3 kg with positive results of direct SARS-CoV-2 viral testing. The FDA has granted emergency use to the first COVID-19 diagnostic test that utilizes breath samples to detect SARS-CoV-2 infection. The federal government is increasing availability of oral antivirals for COVID-19. Please refer to the COVID-19 disclaimer at the end of the publication.
The efficacy and safety of tirzepatide was evaluated in 5 phase 3 trials either alone or in combination with other diabetes medications. Tirzepatide 5 mg, 10 mg, and 15 mg were compared to placebo, the GLP-1 receptor agonist semaglutide (Ozempic®, 1 mg), and long-acting insulin analogs (insulin glargine and insulin degludec). Tirzepatide 15 mg resulted in a reduction in HbA1c 0.5% greater than semaglutide, 0.9% greater than insulin degludec, and 1% greater than insulin glargine. The HbA1c reduction with 15 mg tirzepatide as monotherapy was 1.6% greater than placebo and 1.5% greater than placebo when given in combination with a long-acting insulin. The average weight loss with 15 mg tirzepatide ranged from 12 pounds more than with semaglutide to 29 pounds more than with insulin degludec. 2 | JUNE 2022
» June 7th – Novavax COVID-19 vaccine EUA request to prevent COVID-19 in recipients ≥ 18 years old » June 14th – Moderna EUA request for 6 to 17 years old » June 15th – Moderna (6 months to 5 years old) and Pfizer/Biontech (6 months to 4 years old) EUA requests » June 28th – Modification of SARS-CoV-2 strain composition for COVID-19 vaccines discussion
DRUG INFORMATION
HAPPENINGS & HIGHLIGHTS • The FDA has announced its confidence in manufacturers’ ability to now provide varenicline (Chantix®) supply with the N-nitroso-varenicline impurity ≤ 37 ng/day (acceptable intake limit). The shortage of varenicline has resolved. • Pfizer has voluntarily recalled 5 lots of Accupril® (quinapril HCl) tablets to the patient level due to the presence of N-nitroso-quinapril above the acceptable daily intake level. The lots were distributed from December 2019 to April 2022. • TG Therapeutics has voluntarily withdrawn umbralisib (Ukoniq®) from sale in the US. Umbralisib received Accelerated Approval in February 2021 for the indications of adults with marginal zone lymphoma (MZL) who have received ≥ 1 prior anti-CD20-based regimen and adults with follicular lymphoma (FL) who have received ≥ 3 prior systemic therapies. The discontinuation follows TG Therapeutics’s decision to withdraw its pending application for the combination of umbralisib and ublituximab based on updated overall survival data from the UNITY-CLL phase 3 trial.
• The FDA has approved a new indication for baricitinib (Olumiant®) for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or ECMO. It is also indicated for certain adults with moderately- to severely-active rheumatoid arthritis. The recommended dosage for COVID-19 is 4 mg once daily for up to 14 days. A 4 mg tablet strength was also approved to correspond with the new indication. Approval marks the first FDA-approved immunomodulatory therapy for COVID-19. • A new dosage regimen has been approved for nivolumab (Opdivo®) 360 mg every 3 weeks in combination with ipilimumab (Yervoy®) 1 mg/kg every 6 weeks. This new regimen is for the approved indication of metastatic non-small cell lung cancer expressing PD-L1 (≥ 1%) as determined by an FDAapproved test, with no EGFR or ALK genomic tumor aberrations, as first-line treatment. Previously, the dose for nivolumab was 3 mg/kg every 2 weeks for this indication.
DRUG INFORMATION HAPPENINGS • The FDA has released an update on nirmatrelvir and ritonavir (Paxlovid™) for HCPs. • Clinical practice guideline recommendations have been published in The BMJ on the use of PCSK9 inhibitors and ezetimibe for reduction of cardiovascular (CV) events. • The Institute for Clinical and Economic Review (ICER) has published a Final Evidence Report on the clinical effectiveness and value of the following COVID-19 outpatient treatments: molnupiravir, Paxlovid, and fluvoxamine. • The US Preventive Services Task Force (USPSTF) has issued a final recommendation statement on use of aspirin to prevent cardiovascular disease (CVD). For adults ≥ 60 years, initiating low-dose aspirin use for the primary prevention of CVD is recommended against (Grade D). For adults aged 40 to 59 years with a ≥ 10% ten-year cardiovascular disease (CVD) risk, the decision to initiate low-dose aspirin use for the primary prevention of CVD should be individualized, as the net benefit in this group is small; those not at an increased bleeding risk and willing to take it daily are more likely to receive a benefit (Grade C).
PIPELINE
NEWS
UPCOMING PRESCRIPTION DRUG/BIOSIMILAR USER FEE ACT (PDUFA/BsUFA) DATES DRUG NAME MANUFACTURER
FORMULATION THERAPEUTIC CLASS
PROPOSED CLINICAL USE
ANTICIPATED FDA APPROVAL
spesolimab Boehringer Ingelheim
• IV, SC • Interleukin-36 receptor (IL-36R) antagonist
Generalized pustular psoriasis flares
Jun–Jul 2022
sodium phenylbutyrate Acer
• Oral • Nitrogen-binding agent
Urea cycle disorders
06/03/2022
sodium phenylbutyrate/ taurursodiol Amylyx
• Oral • Nitrogen-binding agent / BCL2-associated X protein (Bax) inhibitor
Amyotrophic lateral sclerosis
06/29/2022
4 | JUNE 2022
RECENT FDA
APPROVALS DRUG NAME MANUFACTURER
DESCRIPTION
New Drugs benzoyl peroxide (Epsolay®) Sol-Gel/Galderma
oteseconazole (Vivjoa™) Mycovia
• • • • •
505(b)(2) NDA approval 04/22/2022; Standard Review Indicated for the treatment of inflammatory lesions of rosacea in adults Oxidizing agent Topical cream: 5% in a 50 gram pump Recommended dosage is to apply a pea-sized amount once daily to clean and dry skin as a thin layer to each area of the face (forehead, chin, nose, each cheek)
• NDA approval 04/26/2022; Fast Track, Priority Review, Qualified Infectious
Disease Product
• Indicated to reduce the incidence of recurrent vulvovaginal candidiasis (RVVC)
in females with a history of RVVC who are NOT of reproductive potential
• Azole antifungal • Oral capsule: 150 mg • Two recommended dosage regimens: » Oteseconazole 600 mg as a single dose on day 1, then oteseconazole 450 mg
as a single dose on day 2, and then oteseconazole 150 mg every 7 days for 11 weeks beginning on day 14; administer all doses orally with food » Oral fluconazole (not supplied with product) 150 mg on days 1, 4, and 7, then oteseconazole 150 mg once daily for 7 days on days 14 through 20, then oteseconazole 150 mg every 7 days for 11 weeks (starting on day 28); administer all oteseconazole doses orally with food • Product availability is expected in 2Q 2022 mavacamten (Camzyos™) Bristol-Myers Squibb
• NDA approval 04/28/2022; Breakthrough Therapy, Orphan Drug, Standard
Review
• Indicated for the treatment of adults with symptomatic New York Heart
• • •
•
Association (NYHA) class II to III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms Cardiac myosin inhibitor Oral capsule: 2.5 mg, 5 mg, 10 mg, 15 mg Dosage must be individualized based on clinical status and echocardiographic assessment of patient response; recommended starting dosage of 5 mg once daily with titration to doses of 2.5 mg, 5 mg, 10 mg, or 15 mg once daily; initiation phase of ≥ 12 weeks with dosing adjustments every 4 weeks, as appropriate; maintenance phase adjustments may occur every 12 weeks; see PI for details Boxed warning for risk of heart failure; only available through REMS program
RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER
DESCRIPTION
New Drugs continued trientine tetrahydrochloride (Cuvrior™) Orphalan
• 505(b)(2) NDA approval 04/28/2022; Orphan Drug, Standard Review • Indicated for the treatment of adult patients with stable Wilson’s disease who are de-coppered and tolerant to penicillamine • Copper chelator • Oral tablet: 300 mg, functionally scored; not substitutable for other trientine formulations on a mg-to-mg basis • Recommended daily dosage is 300 mg to 3,000 mg (maximum dose) in 2 divided doses (the higher dose, if applicable, should be taken as the first daily dose) on an empty stomach; see PI for detailed dosage recommendations when switching from penicillamine • Product availability is expected by early 2023
vonoprazan/amoxicillin (Voquezna™ Dual Pak™) Phathom
• 505(b)(2) NDA approval 05/03/2022; Priority Review, Qualified Infectious Disease Product • Indicated for the treatment of Helicobacter pylori infection in adults; should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria to reduce the development of drug-resistant bacteria and maintain the effectiveness • Combination of a potassium-competitive acid blocker and a penicillin class antibacterial • 14-day carton containing 28 vonoprazan 20 mg oral tablets co-packaged with 84 amoxicillin 500 mg oral capsules: each day contains 2 vonoprazan 20 mg tablets and 6 amoxicillin 500 mg capsules • Recommended daily dosage is vonoprazan 20 mg twice daily (morning and evening) and amoxicillin 1,000 mg (2 capsules) three times a day (morning, mid-day, and evening) with or without food for 14 days • Product availability is expected in 3Q 2022
vonoprazan/amoxicillin/ clarithromycin (Voquezna™ Triple Pak™) Phathom
• 505(b)(2) NDA approval 05/03/2022; Priority Review, Qualified Infectious Disease Product • Indicated for the treatment of H. pylori infection in adults; should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria to reduce the development of drug-resistant bacteria and maintain the effectiveness • Combination of a potassium-competitive acid blocker, a penicillin class antibacterial, and a macrolide antibacterial • 14-day carton containing 28 vonoprazan 20 mg oral tablets co-packaged with 56 amoxicillin 500 mg oral capsules and 28 clarithromycin 500 mg oral tablets: each day contains 2 vonoprazan 20 mg tablets, 4 amoxicillin 500 mg capsules, and 2 clarithromycin 500 mg tablets • Recommended daily dosage is vonoprazan 20 mg twice daily (12 hours apart), amoxicillin 1,000 mg (2 capsules) twice daily (12 hours apart), and clarithromycin 500 mg twice daily (12 hours apart) with or without food for 14 days • Product availability is expected in 3Q 2022
6 | JUNE 2022
RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER
DESCRIPTION
New Drugs continued edaravone (Radicava ORS®) Mitsubishi Tanabe
• • • • •
NDA approval 05/12/2022; Fast Track, Orphan Drug, Priority Review Indicated for the treatment of amyotrophic lateral sclerosis (ALS) Antioxidant Oral suspension: 105 mg/5 mL in a multi-dose amber glass bottle Recommended dosage is 105 mg orally (or via feeding tube) in the morning after overnight fasting; food should not be consumed for 1 hour following administration but water is permissible; initially administered as a 14-day treatment cycle, followed by a 14-day drug-free period; subsequent treatment cycles are for 10 days out of 14-day periods, followed by 14 days drug-free
tapinarof (Vtama®) Dermavant
• • • • • •
NDA approval 05/23/2022; Standard Review Indicated for the topical treatment of plaque psoriasis in adults Aryl hydrocarbon receptor agonist Topical cream: 1% in a 60 gram laminated tube Recommended dosage is to apply as a thin layer to affected areas once daily Product availability is expected in June 2022
treprostinil (Tyvaso DPI™) United Therapeutics
• NDA approval 05/23/2022; Orphan Drug, Priority Review • Indicated for the treatment of (1) pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability (studies establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH [56%] or PAH associated with connective tissue diseases [33%]); and (2) pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability (study establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia [45%] inclusive of idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema [25%], and WHO Group 3 connective tissue disease [22%]) • Prostacyclin mimetic • Inhalation powder: single-dose plastic cartridges containing 16, 32, 48, or 64 mcg of treprostinil as a dry powder formulation to be administered with the Tyvaso DPI inhaler • Recommended dosage is to administer as 4 separate treatment sessions each day approximately 4 hours apart, during waking hours, beginning with a dose of 16 mcg/session and increasing by an additional 16 mcg/session at approximately 1 to 2 week intervals as tolerated to a maintenance dose range of 48 mcg to 64 mcg/session 4 times daily; administer using a single inhalation per cartridge • Product availability is expected in June 2022
505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.
7 | JUNE 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: ALK anaplastic lymphoma kinase
HbA1c hemoglobin A1c
Q quarter
BLA Biologics License Application
HCl hydrochloride
REMS Risk Evaluation and Mitigation Strategy
BMJ British Medical Journal
HCP healthcare professional
CDC Centers for Disease Control and Prevention
IV intravenous
SARS-CoV-2 severe acute respiratory syndrome coronavirus 2
COVID-19 Coronavirus Disease 2019
NDA New Drug Application
ECMO extracorporeal membrane oxygenation
NIH National Institutes of Health
EGFR epidermal growth factor receptor
PCSK9 proprotein convertase subtilisin/kexin 9
EUA Emergency Use Authorization
PD-L1 programmed death-ligand 1
FDA Food and Drug Administration
PI prescribing information
References: fda.gov
whitehouse.gov
8 | JUNE 2022
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SC subcutaneous US United States VRBPAC Vaccines and Related Biological Products Advisory Committee WHO World Health Organization