Alhemo Approved for Hemophilia with Inhibitors

The US Food and Drug Administration (FDA) approved Novo Nordisk’s Alhemo^® (concizumab-mtci) on Dec. 20, 2024. Used 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 with factor VIII inhibitors or hemophilia B with factor IX inhibitors, it is the first treatment to be injected subcutaneously (SC) once daily based on weight and plasma concentration levels in this population. A tissue factor pathway inhibitor (TFPI) antagonist, Alhemo reduces the activity of TFPI, a protein that keeps blood from clotting and increases the availability of thrombin. There is a risk of thromboembolic events with treatment. Full prescribing information may be found here.

At a Glance

• Brand Drug: Alhemo^® (concizumab-mtci)
• Manufacturer: Novo Nordisk
• Date Approved: Dec. 20, 2024
• Indication:  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 (congenital factor VIII deficiency) with FVIII inhibitors and hemophilia B (congenital factor IX deficiency) with FIX inhibitors
• Dosage Forms Available: Single-patient-use prefilled pen available in 60mg/1.5mL (40mg/mL), 150mg/1.5mL (100mg/mL), and 300mg/3mL (100mg/mL)
• Launch Date: Unknown at this time
• Estimated Annual Cost: Not available at this time.
• FDA Designation: Breakthrough Therapy. Orphan Drug. Priority Review.
• Hemophilia, which includes several inherited bleeding disorders, results from genetic mutations. Hemophilia A is caused by insufficient activity of coagulation factor VIII, while hemophilia B results from deficiencies of factor IX. Either form of the condition involves excessive bleeding episodes that cause intense pain, permanent joint damage, and potentially life-threatening hemorrhages.
• Hemophilia A is the more common type of the condition, affecting around 25,000 patients – mostly boys and men – in the US. Up to 7,500 American patients, also including a few females, are estimated to have hemophilia B. The average patient age is about 24 years old, and approximately 40% of patients have severe forms of hemophilia.
• Treatment for hemophilia involves replacing the missing clotting factor via intravenous (IV) infusion; however, the body may produce an immune response to the clotting factors, inhibitors, causing the clotting factors not to work. As many as 35% of patients who have severe hemophilia A, but less than 5% of those who have severe hemophilia B, develop inhibitors.
• The pivotal phase III trial supporting this approval showed an 86% reduction in annualized bleed rate in patients receiving Alhemo prophylaxis compared to no prophylaxis (p<0.001). Injection site reactions and urticaria were the most common adverse events reported.
• To treat hemophilia with inhibitors, some patients inject high doses of their usual clotting factor or use a bypassing agent (BPA), such as activated prothrombin complex concentrate (aPCC). Two recombinant activated factor VII products, NovoSeven^® RT (coagulation factor VIIa [recombinant] and Sevenfact^® (coagulation factor VIIa [recombinant]-jncw) also treat either type of hemophilia that has developed inhibitors. Both are used after bleeds have started and either may need several doses – given at intervals of as little as two hours apart.
• Another anti-TFPI, Pfizer’s Hympavzi^® (marstacimab), was approved in October for the treatment of people with severe hemophilia A or B, without inhibitors. Novo Nordisk’s NN-7769 (Mim8) is a bi-specific monoclonal antibody that targets activated factor IX (FIXa) and factor X (FX) (similar to Hemlibra) that is in Phase III development to prevent bleeding episodes in patients with hemophilia A. It’s administered as a SC injection once weekly or once monthly. Approval is possible in 2025. There are additional gene therapies for hemophilia A and hemophilia B that could reach the market in 2025.