FDA Approves First Non-Factor, Once-Weekly Treatment for Hemophilia A and B

On October 11, the FDA approved marstacimab-hncq, the first non-factor, once-weekly treatment for hemophilia B. This new therapy is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients aged 12 years and older with hemophilia A without factor VIII inhibitors, or hemophilia B without factor IX inhibitors.

“Today’s approval … 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,” Ann Farrell, MD, director of the Division of Non-Malignant Hematology in the FDA’s Center for Drug Evaluation and Research, said in a press release. “This new type of treatment underscores the FDA’s commitment to advance the development of innovative, safe, and effective therapies.”

Hemophilia A and B are genetic disorders that impair the body’s ability to form blood clots due to deficiencies in clotting factors VIII (FVIII) and IX (FIX), respectively. Patients with these disorders experience prolonged bleeding after injuries or surgeries, and may suffer spontaneous bleeding episodes, which can be life-threatening. Until now, treatment has involved episodic or prophylactic replacement of FVIII or FIX or the use of products that mimic these factors.

Marstacimab-hncq introduces a novel approach by reducing the activity of a naturally occurring anticoagulation protein called tissue factor pathway inhibitor (TFPI), which increases thrombin generation—an enzyme essential for blood clotting. By enhancing thrombin production, marstacimab-hncq is expected to reduce the frequency of bleeding episodes.

The FDA approval was supported by an open-label, multi-center study involving 116 male patients with severe hemophilia A or B, without inhibitors. The study evaluated the efficacy of marstacimab-hncq by comparing the annualized bleeding rates (ABR) in patients receiving on-demand or prophylactic factor replacement with those receiving marstacimab-hncq. In patients initially on on-demand treatment, the ABR was significantly reduced from 38 to 3.2 after switching to marstacimab-hncq. In patients who had been receiving prophylactic factor replacement, marstacimab-hncq maintained similar bleeding rates, with the ABR decreasing from 7.85 to 5.08.

Marstacimab-hncq comes with warnings and precautions regarding potential thromboembolic events, hypersensitivity reactions, and embryofetal toxicity. The most common side effects are injection site reactions, headache, and itching.

Reference:

FDA approves new treatment for hemophilia A or B. News release. US Food and Drug Administration; October 11, 2024. Accessed October 22, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-hemophilia-or-b