NOVEMBER 2023
CLINICAL
ALERT
Your Monthly Source for Drug Information Highlights EDITORIAL STAFF EDITOR-IN-CHIEF Maryam Tabatabai PharmD EXECUTIVE EDITOR Anna Schreck Bird PharmD DEPUTY EDITORS Carole Kerzic RPh Olivia Pane PharmD, CDCES
TRENDING TOPICS WEIGHT MANAGEMENT CORNER COVID-19 NOTABLES BIOSIMILAR UPDATES DRUG INFORMATION HAPPENINGS & HIGHLIGHTS PIPELINE NEWS RECENT FDA APPROVALS
TRENDING TOPICS HOT TOPIC – STEM CELL THERAPY FOR ALS
BIOSIMILAR CORNER: UPDATES
An advisory committee (ad com) to the FDA reviewed the BLA for Brainstorm Cell Therapeutics’ investigational mesenchymal stem cell therapy, debamestrocel (NurOwn®), for the treatment of amyotrophic lateral sclerosis (ALS). The ad com voted that there was not substantial evidence to demonstrate efficacy for the treatment of mild to moderate ALS. Although the FDA is not required to follow the ad com’s recommendations, their findings are generally considered during the review process. The FDA’s decision is expected by 12/08/2023.
Adalimumab-afzb (Abrilada™) has been designated by the FDA as an interchangeable biosimilar to the corresponding presentations of adalimumab (Humira®): 10 mg/0.2 mL and 20 mg/0.4 mL prefilled syringe; 40 mg/0.8 mL prefilled glass syringe, prefilled pen, and SDV. This interchangeable designation applies to all indications: RA, JIA, PsA, AS, CD, UC, PsO, HS, and UV. Ranibizumabnuna (Byooviz™) for intravitreal injection has also been designated by the FDA as an interchangeable biosimilar to the corresponding presentation of ranibizumab injection (Lucentis®) for the following indications: neovascular (wet) AMD, macular edema following RVO, and mCNV.
SPECIALTY DRUG UPDATE The FDA has approved a single-dose prefilled syringe and single-dose prefilled pen of vedolizumab (Entyvio®) in the strength of 108 mg/0.68 mL for SC self-injection for maintenance therapy in adults with moderately to severely active UC. Previously, vedolizumab was only available for IV injection. The IV route of administration is indicated for UC and CD. Secukinumab (Cosentyx®) has received FDA approval as the first IV formulation IL-17A antagonist for the treatment of adults with active PsA, AS, and non-radiographic axial spondyloarthritis with objective signs of inflammation. Previously, it was only indicated for SC administration. IV product is given monthly by an HCP over 30 minutes.
WEIGHT MANAGEMENT CORNER A research letter published in JAMA reported on data from a cohort study including new users of GLP-1 receptor agonists semaglutide (n=613) and liraglutide (n=4,144) and active comparator bupropion/naltrexone (n=654). They found that use of GLP-1 receptor agonists was associated with increased risk of pancreatitis, gastroparesis, and bowel obstruction, but not biliary disease, compared with bupropion/naltrexone. Novo Nordisk has announced early cessation of the randomized, double-blind, placebo-controlled, superiority FLOW trial (n=3,534) based on interim efficacy results. FLOW compared semaglutide 1 mg SC weekly to placebo as adjunct to standard of care in patients with T2DM and CKD for prevention of renal impairment progression and risk of renal and CV mortality. 2 | NOVEMBER 2023
RSV SPOTLIGHT The CDC released a Health Advisory with interim recommendations on nirsevimab (Beyfortus™) for the 2023–2024 RSV season due to limited supply. Prioritize nirsevimab 100 mg doses for infants at highest risk for severe RSV disease: < 6 months old, American Indian and Alaska Native infants < 8 months old, and infants 6 to < 8 months old with underlying conditions. Two 50 mg doses should not be used for infants weighing ≥ 5 kg (≥ 11 lbs) to preserve supply for infants weighing < 5 kg (< 11 lbs). The 50 mg dose recommendations remain unchanged.
COVID-19: NOTABLE DEVELOPMENTS The FDA has amended the EUA for Novavax COVID-19 Vaccine, Adjuvanted for use in individuals ≥ 12 years of age to include the 2023–2024 formula. Those ≥ 12 years of age previously vaccinated with a COVID-19 vaccine who have not already received a recently updated mRNA COVID-19 vaccine can receive 1 dose; unvaccinated individuals would receive 2 doses. The CDC has stopped distributing COVID-19 vaccination cards. Patients who require a copy of their full vaccination record should contact their state health department’s immunization information system. HHS launched the Bridge Access Program to allow for free COVID-19 vaccination for uninsured and underinsured adults. The temporary program, administered through the CDC, will end in December 2024. Please refer to the COVID-19 disclaimer at the end of this publication.
DRUG INFORMATION HAPPENINGS & HIGHLIGHTS • KVK-Tech has voluntarily recalled 1 lot of betaxolol tablets, USP 10 mg, to the consumer level following an oxycodone HCl tablet (5 mg) being found on the packaging line. The manufacturer has not received reports of a foreign tablet in any betaxolol bottles. • The FDA has approved the Empaveli® Injector, a singleuse, on-body SC device for self-administration of pegcetacoplan (Empaveli) into the abdomen over 30 to 60 minutes. Pegcetacoplan is indicated for adults with paroxysmal nocturnal hemoglobinuria and can also be administered with an infusion pump. • The FDA has issued a warning to patients and HCPs regarding potential risks associated with use of compounded ketamine products (including oral formulations) for the treatment of psychiatric disorders. Ketamine is not FDA-approved for any psychiatric disorder as it has not been established as safe nor effective for these uses. • Scynexis has voluntarily recalled 2 lots of ibrexafungerp (Brexafemme®) tablets to the consumer level due to potential cross contamination with a non-antibacterial beta-lactam drug substance in the active ingredient used to manufacture the product. The potential cross contamination could result in hypersensitivity reactions (e.g., swelling, rash, urticaria, anaphylaxis).
• Takeda is taking steps to voluntarily withdraw mobocertinib (Exkivity®) based on data from the phase 3 EXCLAIM-2 confirmatory trial which did not meet the primary endpoint. It is indicated for adults with EGFR Exon20 insertion mutation-positive locally advanced or metastatic NSCLC whose disease has progressed on or after platinum-based chemotherapy. • Results from a multi-clinic, prospective study evaluating an autism screening digital application (app) (SenseToKnow app) administered at pediatric well-child visits to 475 children 17 to 36 months of age showed high diagnostic accuracy (sensitivity, 87.8%; specificity, 80.8%; negative predictive value, 97.8%; positive predictive value, 40.6%). A total of 49 of the toddlers were subsequently diagnosed with autism and 98 were diagnosed with developmental delay without autism. A high level of accuracy for classification of autism versus neurotypical development was demonstrated (AUC, 0.9; CI, 0.87 to 0.93). Comparable sensitivity performance was seen across subgroups with the app that uses video and touch data. • Vistapharm issued a recall of 1 lot of the antiulcer drug sucralfate oral suspension, 1 g/10 mL, to the consumer level following Bacillus cereus contamination. Microbial contamination could lead to disseminated, life-threatening infections (e.g., endocarditis, necrotizing soft tissue infections) in immunocompromised patients.
DRUG INFORMATION HAPPENINGS • The ACP has published version 2 of the clinical guidelines on outpatient treatment of confirmed COVID-19. • The CDC published an MMWR on the interim effectiveness of 2023 Southern Hemisphere influenza vaccines in preventing influenza-associated hospitalization from March 2023 to July 2023; the vaccines decreased the risk of influenza-associated hospitalizations by 52%. • The FDA launched a pilot program to aid in the development of treatments for rare diseases. • ICER published a Special Report on apixaban (Eliquis®) and rivaroxaban (Xarelto®) for nonvalvular atrial fibrillation (NVAF). The report was submitted to CMS as a component of Medicare drug price negotiations. • ICER has released 2023 updates to its Value Assessment Framework document that includes final updates for the procedures and methodology that will be used to develop future ICER assessments.
PIPELINE NEWS UPCOMING PRESCRIPTION DRUG/BIOSIMILAR USER FEE ACT (PDUFA/BsUFA) DATES DRUG NAME MANUFACTURER
FORMULATION THERAPEUTIC CLASS
PROPOSED CLINICAL USE
ANTICIPATED FDA DECISION
chikungunya monovalent, live attenuated vaccine Valneva
• IM • Viral vaccine
Chikungunya virus immunization
November 2023
taurolidine/heparin Cormedix
• IV • Antimicrobial/anticoagulant
Reduction of catheterrelated bloodstream infections (CRBSIs) related to chronic hemodialysis
11/15/2023
TAK-755 Takeda
• IV • Enzyme replacement
Congenital thrombotic thrombocytopenic purpura (cTTP)
11/16/2023
vonoprazan Phathom
• Oral • Potassium-competitive acid
Erosive gastroesophageal reflux disease
11/17/2023
reproxalap Aldeyra
• Ophthalmic • Aldehyde inhibitor
Dry eye disease
11/23/2023
nirogacestat Springworks/GlaxoSmithKline
• Oral • Gamma secretase inhibitor
Desmoid tumors
11/27/2023
repotrectinib Bristol-Myers Squibb
• Oral • Anaplastic lymphoma kinase
NSCLC (ROS1-positive, metastatic, previously treated with one ROS1 tyrosine kinase inhibitor and who have not received prior platinumbased chemotherapy)
11/27/2023
fruquintinib Takeda
• Oral • Vascular endothelial growth
Colorectal cancer (refractory, metastatic, ≥ 2nd-line)
11/30/2023
4 | NOVEMBER 2023
blocker
(ALK) inhibitor; Tropomyosin receptor kinase (TRK) inhibitor
factor receptor (VEGFR) inhibitor
RECENT FDA APPROVALS DRUG NAME MANUFACTURER
DESCRIPTION
New Drugs nedosiran (Rivfloza™) Novo Nordisk
• NDA approval 09/29/2023; Orphan Drug, Standard Review • Indicated to lower urinary oxalate levels in children ≥ 9 years of age and adults
tocilizumab-bavi (Tofidence™) Biogen
• BLA approval 09/29/2023; 1st biosimilar to tocilizumab (Actemra®) • Indicated for the treatment of: » Adults with moderately to severely active RA who have had an inadequate
with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function (e.g., eGFR ≥ 30 mL/min/1.73 m2) • Lactate dehydrogenase A (LDHA)-directed small interfering RNA • Solution for injection: 160 mg/mL in 80 mg (0.5 mL) SDV and 128 mg (0.8 mL) and 160 mg (1 mL) single-dose pre-filled syringes • Recommended dosage is given SC once per month by an HCP, caregiver, or patient depending on the formulation and the patient’s age; dose is based on patient’s age and body weight » Patients ≥ 12 years of age: 128 mg once monthly if < 50 kg or 160 mg once monthly if ≥ 50 kg » Children 9 to 11 years of age: 3.3 mg/kg once monthly (not to exceed 128 mg) if < 50 kg or 160 mg once monthly if ≥ 50 kg • Product availability is expected in early 2024
response to ≥ 1 disease-modifying anti-rheumatic drugs (DMARDs)
» Patients ≥ 2 years of age with active polyarticular JIA (PJIA) or active systemic
JIA (SJIA)
• Interleukin-6 (IL-6) receptor antagonist • Solution for injection: 80 mg/4 mL, 200 mg/10 mL, 400 mg/20 mL in SDVs for
further dilution prior to IV infusion by an HCP • Recommended starting dosage for adults with RA when used in combination with DMARDs or as monotherapy is 4 mg/kg every 4 weeks followed by an increase to 8 mg/kg every 4 weeks based on clinical response (doses > 800 mg per infusion are not recommended) • For pediatric patients with PJIA and SJIA, dosing is weight-based every 2 weeks (SJIA) or every 4 weeks (PJIA) • Boxed warning for risk of serious infections
RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER etrasimod (Velsipity™) Pfizer
DESCRIPTION • NDA approval 10/12/2023; Standard Review • Indicated for the treatment of moderately to severely active UC in adults • Sphingosine 1-phosphate (S1P) receptor modulator • Oral tablet: 2 mg • Recommended dosage is 2 mg orally once daily; recent CBC (including lymphocyte
count), ECG, transaminase and bilirubin levels, ophthalmic evaluation, and skin examination are recommended prior to initiating etrasimod
bimekizumab-bkzx (Bimzelx®) UCB
• BLA approval 10/17/2023; Standard Review • Indicated for the treatment of moderate to severe PsO in adults who are
candidates for systemic therapy or phototherapy
• Humanized interleukin-17A and F antagonist • Injection: 160 mg/mL solution in a single-dose prefilled syringe or single-dose
prefilled autoinjector
• Recommended dosage is 320 mg (two 160 mg injections) by SC injection at
weeks 0, 4, 8, 12, and 16, then every 8 weeks thereafter; for patients weighing ≥ 120 kg, consider a dose of 320 mg every 4 weeks after week 16; patients can self-inject after training in injection technique and can administer into the thighs, abdomen, or back of upper arm • Prior to initiation, evaluate liver enzymes, alkaline phosphatase and bilirubin as well as screen patients for tuberculosis infection and ensure all age-appropriate vaccinations have been completed • Product availability is expected in November 2023 pilocarpine HCl (Qlosi™) Orasis
• NDA approval 10/17/2023; Standard Review • Indicated for the treatment of presbyopia in adults • Cholinergic agonist • Ophthalmic solution: 0.4% (4 mg/mL) in single-patient-use vial • Recommended dosage is 1 drop in each eye and can be repeated a 2nd time
after 2 to 3 hours for an effect up to 8 hours; it can be used on a daily basis, or as needed, up to two-times each day • Product availability is expected in the 1H of 2024 tenapanor (Xphozah®) Ardelyx
6 | NOVEMBER 2023
• NDA approval 10/17/2023; Standard Review • Indicated to reduce serum phosphorus in adults with CKD on dialysis as add-on
therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy • Sodium hydrogen exchanger 3 (NHE3) inhibitor • Oral tablet: 10 mg, 20 mg, 30 mg • Recommended dosage is 30 mg twice daily before the morning and evening meals; monitor serum phosphorus and adjust the dose as needed to manage gastrointestinal tolerability • Product availability is expected in November 2023
RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER zilucoplan (Zilbrysq®) UCB
DESCRIPTION • NDA approval 10/17/2023; Orphan Drug, Standard Review • Indicated for the treatment of generalized myasthenia gravis (gMG) in adults
who are anti-acetylcholine receptor (AChR) antibody positive
• Complement inhibitor • Solution for injection: 16.6 mg/0.416 mL, 23 mg/0.574 mL, 32.4 mg/0.81 mL
single-dose prefilled syringes
• Recommended dosage is given SC based on patient’s body weight ranging from
16.6 mg once daily to 32.4 mg once daily; patients can self-inject after training in injection technique and can administer into the abdomen, thighs, or back of the upper arms with rotation of injection sites for each administration • Baseline lipase and amylase levels are recommended prior to initiation as well as meningococcal vaccination ≥ 2 weeks before the 1st dose • Boxed warning for serious meningococcal infections; only available through Zilbrysq REMS sitagliptin (Zituvio™) Zydus
• 505(b)(2) NDA approval 10/18/2023; Standard Review • Indicated as an adjunct to diet and exercise to improve glycemic control in
adults with T2DM
• Not recommended in patients with type 1 diabetes mellitus; not studied in
patients with a history of pancreatitis • Dipeptidyl peptidase-4 (DPP-4) inhibitor • Oral tablet: 25 mg, 50 mg, 100 mg • Recommended dosage is 100 mg once daily with or without food clindamycin phosphate/ adapalene/benzoyl peroxide (Cabtreo™) Bausch Health
• 505(b)(2) NDA approval 10/20/2023; Standard Review • Indicated for the topical treatment of acne vulgaris in patients ≥ 12 years of age • Combination of a lincosamide antibacterial, a retinoid, and benzoyl peroxide • Topical gel: clindamycin 1.2%, adapalene 0.15%, and benzoyl peroxide 3.1% • Recommended dosage is to apply a thin layer to affected skin once daily • Product availability is expected in the 1Q of 2024
infliximab-dyyb (Zymfentra®) Celltrion
• BLA approval 10/20/2023; Standard Review; not a biosimilar to IV-administered
Remicade® (infliximab) • Indicated for the maintenance treatment of adults with moderately to severely active UC or CD, following treatment with an IV-administered infliximab product • Tumor necrosis factor (TNF) blocker • Injection: 120 mg/mL in a single-dose prefilled syringe and pen • Recommended dosage for maintenance treatment is 120 mg SC once every 2 weeks beginning at or after week 10 of infliximab therapy; patients and caregivers may self-inject following proper training; administered into the front of the thigh, abdomen, or outer area of upper arm • Boxed warnings for serious infections and malignancy
RECENT FDA APPROVALS continued DRUG NAME MANUFACTURER oxaprozin (Coxanto™) Solubiomix
DESCRIPTION • 505(b)(2) NDA approval 10/20/2023; Standard Review • Indicated for the relief of the signs and symptoms of osteoarthritis (OA), RA, and
juvenile rheumatoid arthritis (JRA)
• Non-steroidal anti-inflammatory drug (NSAID) • Oral capsule: 300 mg • Recommended dosage for OA and RA is 1,200 mg (4 capsules) once a day; for JRA, the
recommended dosage is 600 mg (2 capsules) once daily in patients weighing 22 kg to 31 kg, 900 mg (3 capsules) once daily in patients 32 kg to 54 kg, and 1,200 mg (4 capsules) once daily in patients ≥ 55 kg • Boxed warnings for risk of serious CV and gastrointestinal events vamorolone (Agamree®) Santhera
• NDA approval 10/26/2023; Orphan Drug, Standard Review • Indicated for the treatment of patients ≥ 2 years of age with Duchenne muscular
dystrophy (DMD)
• Corticosteroid • Oral suspension: 40 mg/mL • Recommended dosage is 6 mg/kg once daily (maximum daily dosage of 300 mg
for patients weighing > 50 kg); some patients may respond to a 2 mg/kg/day dose • Product availability is expected in the 1Q of 2024 505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant. Glossary: ACP American College of Physicians ALS amyotrophic lateral sclerosis AMD age-related macular degeneration AS ankylosing spondylitis AUC area under the curve BLA Biologics License Application CBC complete blood count CD Crohn’s disease CDC Centers for Disease Control and Prevention CI confidence interval CKD chronic kidney disease CMS Centers for Medicare and Medicaid Services COVID-19 Coronavirus Disease 2019 CV cardiovascular ECG electrocardiogram EGFR epidermal growth factor receptor eGFR estimated glomerular filtration rate EUA Emergency Use Authorization FDA Food and Drug Administration GLP-1 glucagon-like peptide 1
H half HCl hydrochloride HCP healthcare professional HHS US Department of Health and Human Services HS hidradenitis suppurativa ICER Institute for Clinical and Economic Review IL-17A interleukin-17A IM intramuscular IV intravenous JAMA The Journal of the American Medical Association JIA juvenile idiopathic arthritis kg kilogram lbs pounds mCNV myopic choroidal neovascularization MMWR Morbidity and Mortality Weekly Report mRNA messenger ribonucleic acid NDA New Drug Application
NIH National Institutes of Health NSCLC non-small cell lung cancer PsA psoriatic arthritis PsO plaque psoriasis Q quarter RA rheumatoid arthritis REMS Risk Evaluation and Mitigation Strategy RNA ribonucleic acid ROS1 ROS proto-oncogene 1, receptor tyrosine kinase RSV respiratory syncytial virus RVO retinal vein occlusion SC subcutaneous SDV single-dose vial T2DM type 2 diabetes mellitus UC ulcerative colitis US United States USP US Pharmacopeia UV uveitis WHO World Health Organization
COVID-19 Disclaimer: For the most current COVID-19 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. Disclaimer: The content in this publication is not a substitute for professional medical advice. For questions regarding any medical condition or if you need medical advice, please contact your healthcare provider. © 2023. Magellan Rx Management, a Prime Therapeutics LLC company. All rights reserved.