EDITORIAL STAFF
EDITOR-IN-CHIEF
Maryam Tabatabai
PharmD
INTERIM EXECUTIVE EDITOR
Olivia Pane
PharmD, CDCES
DEPUTY EDITORS
Jessica Czechowski
PharmD
Carole Kerzic
RPh
Devon Trumbower
PharmD, BCPS
BIOSIMILAR UPDATES
COVID-19 NOTABLES
WEIGHT MANAGEMENT CORNER
DRUG INFORMATION HAPPENINGS & HIGHLIGHTS
PIPELINE NEWS
RECENT FDA APPROVALS
The US FDA has approved two new adeno-associated virus (AAV) vector-based gene therapies; one for Duchenne muscular dystrophy (DMD) and one for hemophilia A. Delandistrogene moxeparvovec-rokl (Elevidys®) is the first gene therapy approved for the treatment of pediatric patients ages 4 through 5 years with DMD and a confirmed mutation in the DMD gene. This agent facilitates production of Elevidys micro-dystrophin, a protein containing select domains of the dystrophin protein found in normal muscle cells. Elevidys is administered by an HCP as a single-dose IV infusion. The recommended dosage is 1.33 x 1014 vector genomes (vg)/kg or 10 mL/kg. The product is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene due to risk of immune-mediated myositis. Elevidys was granted Accelerated Approval based on data from the ongoing SRP-9001-102 (n=41) and SRP-9001-103 (n=20) studies, both of which showed that treatment with Elevidys resulted in statistically significant increases in the surrogate endpoint of Elevidys micro-dystrophin expression in select patients 4 through 5 years of age. Clinical benefit of this agent, including motor function improvement, has not been established.
Valoctocogene roxaparvovec-rvox (Roctavian™) is the first gene therapy approved for the treatment of adults with severe hemophilia A (congenital factor VIII [FVIII] deficiency with FVIII activity < 1 IU/dL) without preexisting antibodies to AAV serotype 5 detected by an FDA-approved test. This gene therapy is administered by an HCP as a one-time IV infusion with a recommended dose of 6 x 1013 vg/kg. Product is available at a concentration of 2 x 1013 vg/mL in a vial containing not less than 8 mL extractable volume. Roctavian contains a viral vector which carries a gene for FVIII; this gene is expressed in the liver to increase FVIII levels and to subsequently reduce the risk of uncontrolled bleeding. The drug carries contraindications for active infection, stage 3 or 4 hepatic fibrosis or cirrhosis, and hypersensitivity to mannitol. Approval was based on the phase 3 GENEr8-1 study in which 112 adult males with hemophilia A received Roctavian therapy and were followed for at least 3 years; results showed that the mean annualized bleeding rate decreased from 5.4 bleeds per year at baseline to 2.6 bleeds per year with Roctavian therapy.
Several biosimilar products to the TNF blocker adalimumab (Humira®) have launched, per manufacturer press releases. Commercially available products include adalimumabadbm ( Cyltezo ® ), adalimumab-bwwd ( Hadlima ™), adalimumab-fkjp (Hulio®), adalimumab-adaz (Hyrimoz®), adalimumab-aacf (Idacio®), adalimumab-aaty (Yuflyma®), and adalimumab-aqvh (Yusimry™). All products are available as low-concentration formulations, except Hyrimoz and Yuflyma. Hadlima, Hyrimoz, and Yuflyma are available as high-concentration formulations. All of these products are citrate-free, with the exception of low-concentration Hadlima. Of these new biosimilars, Cyltezo is the only product that is interchangeable with Humira. Notably, the citrate-free biosimilar adalimumabatto (Amjevita™) launched earlier in 2023.
Adalimumab-bwwd (Hadlima) was recently approved for the treatment of moderate to severe HS in adults. Adalimumab-adbm ( Cyltezo ) and adalimumab-atto (Amjevita) both received FDA approval for the treatment of non-infectious intermediate, posterior, and panuveitis in adults.
The FDA’s VRBPAC voted unanimously in favor of including the XBB.1.5 lineage of the Omicron variant in COVID-19 vaccines for the upcoming fall 2023 season. Manufacturers who will be updating their vaccines have been advised to produce vaccines with a monovalent XBB.1.5 composition.
Novo Nordisk has announced a shortage of liraglutide (Saxenda®) 6 mg/mL pens through the end of 2023 due to increased demand.
The American Society of Anesthesiologists (ASA) released a statement suggesting that patients who are undergoing anesthesia withhold GLP-1RA therapy (e.g., semaglutide, dulaglutide) before elective surgery. This suggestion is based on reports of regurgitation and aspiration of food during anesthesia, likely due to delayed gastric emptying associated with GLP-1RA use. According to the ASA, daily GLP-1RAs should be held on the day of surgery, and weekly GLP-1RAs should be held 1 week before surgery.
• Lecanemab-irmb (Leqembi®) has been converted from Accelerated Approval to full approval for the treatment of Alzheimer’s disease, making it the first amyloid beta-directed antibody to be converted to traditional approval for this indication. This decision was based on results from the phase 3 confirmatory CLARITY AD trial which showed significant slowing of decline in the Clinical Dementia Rating – Sum of Boxes score from baseline to 18 months with Leqembi versus placebo.
• Cipla has issued a voluntary nationwide recall of 6 lots of albuterol sulfate inhalation aerosol, 90 mcg (200 metered inhalation), to the consumer level due to a container defect resulting in failure to deliver the recommended dose. No related adverse events have been reported.
• The Harvard Drug Group has issued a voluntary nationwide recall of 1 lot of dronabinol 2.5 mg capsules and 1 lot of ziprasidone 20 mg capsules to the consumer level due to a label mix-up between the two products. The manufacturer is notifying all direct accounts that were impacted via mail and is arranging for all recalled product to be returned.
• Linaclotide (Linzess®) has been approved as the first treatment for functional constipation (FC) in pediatric patients 6 to 17 years of age. The recommended dose is 72 mcg orally once daily.
• The agency has approved talazoparib (Talzenna®) in combination with enzalutamide (Xtandi®) for the treatment of adults with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer. The recommended dose of talazoparib for this new indication is 0.5 mg orally once daily, taken in combination with enzalutamide 160 mg orally once daily, until disease progression or unacceptable toxicity. Talazoparib capsule strengths of 0.1 mg and 0.35 mg have been approved to accommodate dose reductions.
• Blinatumomab (Blincyto®) has been converted from Accelerated Approval to full approval for the treatment of adult and pediatric patients with CD19-positive B-cell precursor ALL in first or second complete remission with minimal residual disease ≥ 0.1%.
• The FDA has approved norgestrel (Opill®) 0.075 mg tablets for a prescription to OTC switch, making it the first daily oral contraceptive available in the US without a prescription. Consumers will be able to purchase Opill at pharmacies, stores, and online in various package sizes providing a 1-, 2-, 3-, or 6-months’ supply starting in early 1Q 2024.
• The CDC has released a statement which endorses ACIP recommendations for use of RSV vaccines (e.g., Arexvy, Abrysvo™) in patients ≥ 60 years of age after consultation with an HCP.
• The FDA has approved several influenza vaccines for the 2023-2024 season, including the Fluzone® , Fluzone® High-Dose, Flublok®, Afluria®, Fluad®, FluMist®, Flucelvax®, and FluLaval quadrivalent vaccines, and the Afluria trivalent vaccine.
• The North American Menopause Society (NAMS) published a 2023 update to its recommendations for nonhormonal management of menopause-associated vasomotor symptoms. Per NAMS, nonhormonal medications with level 1 evidence include SSRIs, SNRIs, gabapentin, and fezolinetant.
• The USPSTF published a final statement which recommends depression screening for all adults, including those who are pregnant and postpartum (Grade B), and anxiety disorder screening for adults < 65 years of age (Grade B). Evidence is insufficient to recommend for or against suicide risk screening for adults and anxiety disorder screening for adults ≥ 65 years of age.
• IM • Viral vaccine
• SC
• Anti-B cell maturation antigen (BCMA) antibody
• Oral
• Gamma-aminobutyric acid (GABA) modulator
• IV
• Dismutase mimetic
• Oral
• Retinoic acid receptor gamma (RARγ) agonist
mucositis (severe, radiotherapy-induced, in patients with head & neck cancer)
avacincaptad pegol Iveric Bio
pozelimab Regeneron
bevacizumab-vikg Outlook
• Intravitreal
• Complement C5 inhibitor Geographic atrophy secondary to age-related macular degeneration (AMD)
• IV, SC
• Complement C5 inhibitor
• Intravitreal
• Vascular endothelial growth factor (VEGF) inhibitor
CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and severe protein-losing enteropathy (CHAPLE) syndrome
colchicine (Lodoco®)
Agepha
efgartigimod alfa/ hyaluronidase (Vyvgart® Hytrulo) Argenyx
ritlecitinib (Litfulo™)
Pfizer
• 505(b)(2) NDA approval 06/16/2023; Priority Review
• Indicated to reduce the risk of MI, stroke, coronary revascularization, and CV death in adult patients with established atherosclerotic disease or with multiple risk factors for CV disease
• Alkaloid
• Oral tablet: 0.5 mg
• Recommended dosage is 0.5 mg orally once daily
• Product availability is expected in 2H 2023
• BLA approval 06/20/2023; Orphan Drug
• Indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are AChR antibody positive
• Combination neonatal Fc receptor blocker and endoglycosidase
• Injection: 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase per 5.6 mL (180 mg/2,000 units/mL) in a single-dose vial
• Recommended dosage for adults is 1,008 mg/11,200 units (5.6 mL) administered SC by an HCP over 30 to 90 seconds once weekly for 4 weeks, with subsequent treatment cycles based on clinical evaluation
• Safety of initiating subsequent cycles sooner than 50 days from the start of the previous treatment cycle has not been established
• Product is currently available
• NDA approval 06/23/2023; Breakthrough Therapy; Standard Review
• Indicated for the treatment of severe alopecia areata in adults and adolescents ≥ 12 years of age
• Kinase inhibitor
• Oral capsule: 50 mg
• Recommended minimum dosage is 50 mg orally once daily; evaluation is recommended for TB, viral hepatitis, ALC, and up-to-date immunizations prior to initiating treatment
• Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine, or other potent immunosuppressants
• Boxed warnings for serious infections, mortality, malignancy, MACE, and thrombosis
rozanolixizumab-noli (Rystiggo®) UCB
donislecel-jujn (Lantidra) CellTrans
• BLA approval 06/26/2023; Orphan Drug; Priority Review
• Indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are AChR or MuSK antibody positive
• Neonatal Fc receptor blocker
• Injection: 280 mg/2 mL (140 mg/mL) in a single-dose vial
• Recommended dosage is weight-based and HCP-administered, starting at 420 mg (3 mL) for those < 50 kg and up to 840 mg (6 mL) for those ≥ 100 kg as a SC infusion once weekly for 6 weeks
• Safety of initiating subsequent cycles sooner than 63 days from the start of the previous treatment cycle has not been established
• Product availability is expected by Q3 2023
• BLA approval 06/28/2023; Orphan Drug; Standard Review
• Indicated for the treatment of adults with T1DM who are unable to approach target HbA1c because of current repeated episodes of severe hypoglycemia despite intensive diabetes management and education; for use in conjunction with concomitant immunosuppression
• Allogeneic pancreatic islet cellular therapy
• Cell suspension: equivalent islet number (EIN) (maximum of 10 cc of estimated packed islet tissue with not more than 1 x 106 EIN)
• NDA approval 07/24/2023; Standard Review
• Indicated for the treatment of Demodex blepharitis
• Recommended minimum dosage is 5,000 EIN per kg patient body weight for initial IV infusion (transplant) into the hepatic portal vein only; 4,500 EIN/kg for subsequent infusions (same recipient) within 1 year of the previous infusion or within 1 year of losing independence from exogenous insulin lotilaner (Xdemvy™) Tarsus
• Ectoparasiticide (anti-parasitic)
• Ophthalmic solution: lotilaner 0.25% (2.5 mg/mL)
• Recommended dosage is 1 drop in each eye twice daily (approximately 12 hours apart) for 6 weeks
• Product availability is expected by the end of August 2023
505(b)(2) = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.
Glossary:
AChR anti-acetylcholine receptor
ACIP Advisory Committee on Immunization
Practices
ALC absolute lymphocyte count
ALL acute lymphoblastic leukemia
BLA Biologics License Application
CDC Centers for Disease Control and Prevention
CD19 cluster of differentiation 19
CD3 cluster of differentiation 3
CD55 complement decay-accelerating factor
COVID-19 Coronavirus Disease 2019
CV cardiovascular
FDA Food and Drug Administration
GLP-1RA glucagon-like peptide 1 receptor agonist
H half
HbA1c hemoglobin A1c
HCP healthcare professional
HS hidradenitis suppurativa
IU international units
IV intravenous
JAK Janus kinase
MACE major adverse cardiac events
MI myocardial infarction
MuSK antimuscle-specific tyrosine kinase
NDA New Drug Application
OTC over-the-counter
Q quarter
RSV respiratory syncytial virus
SC subcutaneous
SNRI serotonin and norepinephrine reuptake inhibitor
SSRI selective serotonin reuptake inhibitor
T1DM type 1 diabetes mellitus
TB tuberculosis
TNF tumor necrosis factor
US United States
USPSTF United States Preventive Services Task Force
VRBPAC Vaccines and Related Biological Products Advisory Committee
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.
