The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the approval of Alhemo (concizumab) for the treatment of hemophilia A and B in patients 12 years and older with inhibitors. Developed by Novo Nordisk, Alhemo is poised to become the first once-daily subcutaneous prophylactic treatment option for this patient population in the European Union, offering a new approach to managing this rare bleeding disorder.
Mechanism of Action and Clinical Significance
Alhemo is a monoclonal antibody designed to block tissue factor pathway inhibitor (TFPI), a protein that inhibits blood clot formation. By blocking TFPI, concizumab ensures the production of thrombin, which is essential for blood clotting and preventing bleeding episodes. This mechanism is particularly beneficial for hemophilia patients who have developed inhibitors, antibodies that render traditional clotting factor replacement therapies ineffective. It is estimated that inhibitors develop in up to 30% of individuals with severe hemophilia A and 5-10% of those with severe hemophilia B.
Stephanie Seremetis, chief medical officer for hemophilia at Novo Nordisk, stated, "The positive opinion from the CHMP for Alhemo is a major milestone for patients. If approved, Alhemo would be an important addition to our growing hemophilia portfolio as it offers the potential of everyday prophylaxis to prevent bleeds for people living with hemophilia who have developed the complication of inhibitors."
Efficacy Data from the explorer7 Study
The CHMP's positive opinion was supported by data from the Phase 3 explorer7 study, which evaluated the efficacy and safety of Alhemo in individuals with hemophilia A or B with inhibitors. The study's primary analysis compared the annualized bleeding rate (ABR) between patients receiving concizumab prophylaxis and those receiving no prophylaxis. Results demonstrated an 86% reduction in treated spontaneous and traumatic bleeds with concizumab prophylaxis, with a mean ABR of 1.7 compared to 11.8 with no prophylaxis. The overall median ABR with concizumab was zero, compared to 9.8 with no prophylaxis. The safety and tolerability profile of concizumab in this study was within the expected range.
Convenient Administration and Patient Benefits
Alhemo is designed for convenient subcutaneous administration using a pre-filled, multi-use, portable pen that can be stored at room temperature for up to four weeks. This user-friendly design aims to reduce the treatment burden associated with regular intravenous infusions, potentially improving patient adherence and quality of life. "It could alleviate the physical, emotional, and overall treatment burden for people living with hemophilia... This could enable patients to have greater confidence in the pursuit of daily activities, which is especially important for people living with hemophilia B with inhibitors, who currently have very limited treatment options," added Seremetis.
Regulatory Timeline and Market Landscape
Novo Nordisk anticipates a final decision from the European Commission within approximately two months. Alhemo is already approved in Australia, Switzerland, and Japan for certain hemophilia A and B patient populations. In the United States, an application for concizumab is under review by the FDA, with resubmission completed in July 2024. If approved, Alhemo will compete with existing therapies like Roche's Hemlibra (emicizumab) and potentially Pfizer’s Hympavzi (marstacimab), offering a new option for hemophilia management, particularly for patients with inhibitors.
