Marstacimab Gets FDA Nod for Hemophilia A or B Without Inhibitors

The FDA approved marstacimab (Hympavzi) for routine prophylaxis to prevent or reduce bleeding episodes in adults and adolescents ages 12 years and older with hemophilia A without factor VIII inhibitors or hemophilia B without factor IX inhibitors, the agency said Friday.

Marstacimab targets the Kunitz 2 domain of tissue factor pathway inhibitor (TFPI), a natural anticoagulation protein that functions to prevent the formation of blood clots and restore hemostasis. It is the first anti-TFPI approved in the U.S. for the treatment of hemophilia A or B.

“Today’s approval of Hympavzi provides patients with hemophilia a new treatment option that is the first of its kind to work by targeting a protein in the blood clotting process,” said Ann Farrell, MD, director of the Division of Non-Malignant Hematology in the FDA’s Center for Drug Evaluation and Research. “This new type of treatment underscores the FDA’s commitment to advance the development of innovative, safe, and effective therapies.”

The FDA’s decision was based on the phase III BASIS trial of 116 adult and pediatric male patients with either severe hemophilia A or severe hemophilia B, both without inhibitors, who had received usual care with replacement factor either on-demand (33 patients) or as prophylaxis (83 patients) during an observational period. These patients then received marstacimab prophylaxis for 12 months.

Of those who had received treatment on-demand, the annualized bleeding rate (ABR) for treated bleeds fell from a mean of 38 during the observational period to 3.2 after treatment with marstacimab, representing a 91.6% reduction in mean ABR during the 12-month active treatment period.

Among those who had received routine prophylaxis as usual care, the ABR fell from a mean of 7.85 during the observational period to 5.08 after treatment with marstacimab, translating into a 35.2% reduction in mean ABR.

“The approval of Hympavzi is a meaningful advancement for people living with hemophilia A or B without inhibitors for bleed prevention, with a generally manageable safety profile and a straightforward once-weekly subcutaneous administration,” said Suchitra Acharya, MD, director of Northwell Health Hemostasis and Thrombosis Center, Cohen Children’s Medical Center, in New Hyde Park, New York, in a news release from Pfizer, the drug’s developer.

“Hympavzi aims to reduce the current treatment burden by meeting an important need for these patients, including many who have required frequent, time-consuming intravenous treatment infusion regimens,” added Acharya, who was a co-investigator in the BASIS trial.

Marstacimab comes with warnings and precautions about thromboembolic events, hypersensitivity and embryofetal toxicity. Common side effects include injection site reactions, headache, and itching.

Pfizer said the drug is the first once-weekly subcutaneous prophylactic treatment approved for eligible people living with hemophilia B and the first to be administered via a pre-filled pen or syringe for eligible people living with hemophilia A or B in the U.S.