FDA Approves Concizumab-mtci for Prophylaxis in Hemophilia A and B
On December 20, the FDA approved concizumab-mtci for routine prophylaxis to prevent or reduce bleeding episodes in adults and pediatric patients aged 12 years and older with hemophilia A or hemophilia B who have developed inhibitors. This approval provides a new treatment option for a high-risk population with limited alternatives.
Hemophilia A and B are rare genetic bleeding disorders caused by a deficiency in clotting factors VIII and IX, respectively. These disorders lead to prolonged bleeding episodes, which can occur spontaneously or after trauma, surgery, or injury. Hemophilia A accounts for 80-85% of cases, while hemophilia B is less common.
A major complication arises when patients develop inhibitors—antibodies that neutralize the effectiveness of replacement clotting factors. This occurs in approximately 30% of patients with hemophilia A and 5-15% of those with hemophilia B, making traditional replacement therapy ineffective and necessitating alternative treatment strategies.
Concizumab-mtci is a monoclonal antibody designed to address these challenges. By targeting tissue factor pathway inhibitor (TFPI), the drug promotes clot formation independently of factors VIII or IX, bypassing the inhibitor effect. Concizumab-mtci is administered via daily subcutaneous injection, offering a more manageable regimen compared with some traditional therapies.
The approval of concizumab-mtci is supported by robust data from a phase 3 multinational, open-label trial (NCT04083781) involving 133 men with hemophilia A or B and inhibitors. The trial compared patients receiving concizumab-mtci prophylaxis with those without prophylaxis.
The results demonstrated an 86% reduction in annualized bleeding rates (ABR) in the treatment group compared to the no-prophylaxis group, with an estimated ABR ratio of 0.14 (95% CI, 0.07 - 0.29; P <.001).
Concizumab-mtci was well tolerated in clinical trials, with the most commonly reported adverse events being injection site reactions and urticaria, affecting at least 5% of patients. Hypersensitivity reactions such as erythema, rash, itching, and abdominal pain were also observed. Patients with a history of serious hypersensitivity to concizumab-mtci or its components should not use the drug. Additionally, the therapy may increase the risk of blood clots, and patients should be monitored closely for thrombotic events.
Reference
FDA approves drug to prevent or reduce the frequency of bleeding episodes for patients with hemophilia A with inhibitors or hemophilia B with inhibitors. US Food and Drug Administration. December 20, 2024. Accessed December 23, 2024. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-prevent-or-reduce-frequency-bleeding-episodes-patients-hemophilia-inhibitors-or.