The U.S. Food and Drug Administration (FDA) has approved Hympavzi (marstacimab-hncq) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients (12 years of age and older) with hemophilia A without factor VIII inhibitors or hemophilia B without factor IX inhibitors.
Ann Farrell, M.D., Director of the Division of Non-Malignant Hematology in the FDA’s Center for Drug Evaluation and Research, stated, “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. This new type of treatment underscores the FDA’s commitment to advance the development of innovative, safe and effective therapies.”
Hemophilia A and hemophilia B are genetic bleeding disorders caused by a dysfunction or deficiency of coagulation factor VIII (FVIII) or IX (FIX), respectively. Patients with these hemophilias are unable to clot properly and may bleed for a longer time than normal after injury or surgery. They may also have spontaneous bleeding in muscles, joints, and organs, which can be life-threatening. These bleeding episodes are typically managed by either on-demand, episodic treatment or prophylaxis using products containing FVIII or FIX, or a product that mimics a factor.
Mechanism of Action
Hympavzi represents a novel approach to hemophilia treatment. Instead of replacing missing clotting factors, it reduces the activity of tissue factor pathway inhibitor, a naturally occurring anticoagulation protein. By inhibiting this protein, Hympavzi increases thrombin generation, which is critical for effective blood clotting. This mechanism is expected to reduce or prevent the frequency of bleeding episodes.
Clinical Trial Data
The approval of Hympavzi is based on an open-label, multi-center study involving 116 adult and pediatric male patients with severe hemophilia A or B, all without inhibitors. The study evaluated the efficacy of Hympavzi in reducing annualized bleeding rates. During the first six months, patients received either on-demand (33 patients) or prophylactic (83 patients) factor replacement therapy. Subsequently, they were transitioned to Hympavzi prophylaxis for 12 months.
Key findings from the study include:
- In patients initially receiving on-demand factor replacement, the estimated annualized bleeding rate was 38, compared to 3.2 during Hympavzi treatment, demonstrating the superiority of Hympavzi.
- In patients initially receiving prophylactic factor replacement, the estimated annualized bleeding rate was 7.85, which decreased to 5.08 during Hympavzi prophylaxis, indicating similar bleeding rates.
Safety and Adverse Events
The prescribing information for Hympavzi includes warnings and precautions regarding thromboembolic events, hypersensitivity, and embryofetal toxicity. The most common side effects reported were injection site reactions, headache, and itching (pruritus).
Regulatory Information
The FDA granted Hympavzi Orphan Drug designation. The approval was granted to Pfizer Inc.
