Hemophilia is a rare genetic bleeding disorder that affects the body's ability to form blood clots, a process necessary to prevent or stop bleeding. The standard treatment for hemophilia A and B is replacement therapy, which involves administering the missing clotting factor through intravenous infusions of Factor VIII or Factor IX concentrates, depending on whether it is hemophilia A or B, respectively. However, in some cases, the body can develop inhibitors as an immune response to the administered clotting factors, making replacement therapy ineffective and limiting the available treatment options. It is currently estimated that up to 30% of people with severe hemophilia A and 5-10% with severe hemophilia B develop inhibitors. In this context, the impact of the disease on daily life is significant: 75% of people living with moderate or severe hemophilia report that pain affects their daily life, and more than 50% experience multiple spontaneous bleeds over a six-month period.
Now, a medication approved by ANMAT (National Administration of Drugs, Medical Devices and Medical Technology) is available for the routine prophylaxis of hemorrhages in people with hemophilia A and B over 12 years of age who have inhibitors. It is concizumab, a monoclonal antibody administered subcutaneously once a day.
Unlike traditional treatments that replace the missing Factor VIII or IX, this medication blocks a protein in the hemostatic system called TFPI, which normally inhibits the procoagulant process. Its mechanism of action, independent of Factors VIII and IX, allows it to act even in the presence of inhibitors, promoting sustained clot formation.
"The availability of concizumab represents a new way to treat this disease. Until now, this group of patients lacked an effective and safe prophylactic treatment," said Dr. Gabriela Sciuccatti, a pediatric hematologist and former head of the Hematology Service at the Hospital Garrahan.
"The development of inhibitors directly impacts quality of life and treatment complexity, so the possibility of incorporating a non-replacement therapy like concizumab (anti-TFPI) changes the clinical scenario," she added. "This allows us to think about more customized and adapted schemes for the different profiles of people with hemophilia," the specialist concluded.
ANMAT's approval was based on data from the phase 3 explorer7 study, designed to evaluate the drug's efficacy and safety profile in people living with hemophilia A or B with inhibitors. The results showed an 86% reduction in spontaneous and traumatic bleeds in those who received prophylaxis with this medication, with a median estimated Annualized Bleeding Rate (ABR) of 1.7 compared to 11.8 without prophylaxis. The overall median ABR with concizumab was zero, compared to 9.8 without prophylaxis.
The drug's safety and tolerability profile in this study remained within expected parameters, while the drug itself is presented in a prefilled pen, portable and ready to use, allowing for rapid and simple subcutaneous administration, with the aim of alleviating the burden associated with intravenous infusions.
