FDA Updates for the Week of Sept. 25, 2023

FDA Approves New Pompe Therapy

The FDA has approved a two-component therapy — Pombiliti (cipaglucosidase alfa-atga) with Opfolda (miglustat) — to treat adults living with late-onset Pompe disease. It is indicated for those who are not improving on enzyme replacement therapy.

Late-onset Pompe disease is a rare, debilitating, and life-threatening disease that is caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). Reduced levels of GAA lead to the accumulation of glycogen in muscle cells. Disease severity ranges across a spectrum, with skeletal muscle weakness and progressive respiratory involvement being the most common.

Developed by Amicus Therapeutics, Pombiliti is a recombinant human acid alpha-glucosidase (rhGAA) enzyme that is designed for increased uptake into muscle cells where it can help break down glycogen. Opfolda is designed to stabilize the enzyme in the blood. It is available immediately and will have an annual price of $650,000 for a patient weighing about 70 kg. This is a combined price for both products, company executives said. Company executives in an investor call that the price is below current enzyme replacement product, and executives said they will not raise price beyond the Consumer Price Index.

FDA Approves Extended-Release Therapy for Major Depression

The FDA has approved Exxua (gepirone) extended-release tablets to treat adults with major depressive disorder (MDD). Exxua is expected to be available in early 2024.

Major depressive disorder is characterized by low mood, inability to feel pleasure, feelings of worthlessness, and impairment of important functioning. In severe cases, MDD can result in suicide.

Developed by Fabre-Kramer Pharmaceuticals, Exxua is a first-in-class of antidepressant that targets the serotonin 1A receptor, a key regulator of mood and emotion. A spokesperson for Fabre-Kramer said final pricing has not been determined yet but Exxua will be competitive with other branded antidepressants. The company expects formulary placement to also be consistent with newer branded antidepressants, such as Auvelity (dextromethorphan-bupropion), which was approved in August 2022. (Auvelity has a retail price according to GoodRx of about $1,000 for 60 tablets, and it appears that payers may require step therapy and/or prior authorization.)

FDA Sets Review Date for Odronextamab to Treat Blood Cancers

The FDA has granted priority review for Regeneron’s biologics license application (BLA) for odronextamab to treat adult patients with relapsed/refractory follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL). The target action date for the FDA decision is March 31, 2024.

Follicular lymphoma and diffuse large B-cell lymphoma are the two most common subtypes of B-cell non-Hodgkin lymphoma. FL is a slow-growing subtype, and although many patients are responsive to initial treatment, about 20% are expected to relapse within two years. DLBCL is an aggressive subtype, with up to 50% of high-risk patients experiencing progression after first-line treatment.

Odronextamab is an investigational CD20xCD3 bispecific antibody designed to target both CD20 on cancer cells and CD3-expressing T cells.

The BLA was supported by data from a phase 1 and pivotal phase 2 trial (ELM-1 and ELM-2). Results from these studies investigating odronextamab in both FL and DLBCL were presented last year at the American Society of Hematology Annual Meeting.

FDA Approves Drop for Drug-Induced Dilation of the Pupils

The FDA has approved Ryzumvi (phentolamine ophthalmic solution) to treat drug-induced dilation of the pupils. Developed by Viatris and Ocuphire Pharma, Ryzumi is indicated for patients who have received adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) for dilation. It is expected to be available in the first half of 2024. Company officials are not revealing a price at this time, and a company spokesperson pricing information will be available at the time of launch.

Ryzumi, previously called Nyxol by Ocuphire, is a preservative-free formulation of phentolamine that inhibits the contraction of the smooth muscle of the iris.

FDA Grants Priority Review for Sotatercept in Pulmonary Arterial Hypertension

The FDA has accepted for priority review Merck’s biologics license application (BLA) for sotatercept to treat adult patients with pulmonary arterial hypertension (PAH). The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of March 26, 2024.

Pulmonary arterial hypertension is a rare, progressive and life-threatening disease in which blood vessels in the lungs narrow, causing strain on the heart. About 40,000 people in the United States are living with PAH. The five-year mortality rate is about 43%.

PAH is caused by the growth of cells in the arterial walls in the lung, leading to narrowing and abnormal constriction. Sotatercept is a first-in-class activin signaling inhibitor. In preclinical models, it has been shown to modulate vascular cell proliferation, reversing vascular and right ventricle remodeling.

The submission is based on the results of the STELLAR phase 3 trial. Data were presented earlier this year at the American College of Cardiology meeting and published in the New England Journal of Medicine.

FDA Assigns Review Date for Dupixent in Young Children with Eosinophilic Esophagitis

The FDA has accepted for priority review Sanofi’s supplemental biologics license application (sBLA) for Dupixent (dupilumab) to treat children 1 to 11 years of age with eosinophilic esophagitis (EoE). The target action date for the FDA decision is Jan. 31, 2024.

Eosinophilic esophagitis is an inflammatory disease that damages the esophagus. In children, common symptoms include heart burn, vomiting, abdominal discomfort, trouble swallowing, food refusal and failure to thrive.

Dupixent, developed by Regeneron Pharmaceuticals and Sanofi, was approved in May 2022 for patients 12 years and older with eosinophilic esophagitis. Dupixent is a fully human monoclonal antibody that inhibits the signaling of the IL-4 and IL-13 pathways. The sBLA is supported by data from the phase 3 EoE KIDS trial.

Dupixent is also approved to treat moderate-to-severe atopic dermatitis, moderate-to-severe asthma, chronic rhinosinusitis with nasal polyposis and the rare skin disease prurigo nodularis.