The US Food and Drug Administration (FDA) has approved Novo Nordisk’s Alhemo (concizumab‑mtci) injection for once‑daily prophylaxis in adults and adolescents aged 12 years and older with hemophilia A or B (HA/HB) without inhibitors.
This decision builds on the drug’s December 2024 approval for patients with inhibitors, marking a significant expansion of treatment options for the hemophilia community.
“The FDA approval of an expanded indication for Alhemo marks a meaningful step forward for people with hemophilia A or B without inhibitors who are looking for a new prophylaxis treatment option,” said Dr Anna Windle, Senior Vice President, Clinical Development, Medical & Regulatory Affairs, Novo Nordisk.
Following the news, Novo Nordisk’s stock was up by 4.16% on the market trading on 1 August, compared to the market close on the previous day. The Danish company’s stock closed at $48.19, up 2.38% compared to the market close on 31 July.
Understanding Hemophilia and the Treatment Gap
Hemophilia is a rare inherited bleeding disorder affecting around 800,000 people worldwide and roughly 32,000 in the US. It is caused by missing or defective clotting factors, factor VIII in hemophilia A and factor IX in hemophilia B. Without these proteins, the body cannot form stable blood clots, leading to prolonged or spontaneous bleeding episodes.
The current standard‑of‑care for severe cases is prophylactic factor replacement therapy delivered intravenously. However, patients may develop inhibitors, antibodies that neutralize infused clotting factors, rendering standard therapy ineffective. Approximately 30% of those with severe hemophilia A and 5–10% of those with severe hemophilia B develop inhibitors. Even without inhibitors, patients face treatment burdens and the risk of breakthrough bleeds.
Alhemo is a monoclonal antibody that targets tissue factor pathway inhibitor (TFPI), a protein that limits blood clot formation. By inhibiting TFPI, Alhemo enhances factor Xa generation in the early stages of coagulation, improving thrombin production and promoting stable clot formation.
The drug is supplied in prefilled pens for once‑daily subcutaneous injection and can be stored at room temperature for up to 28 days after first use. Recommended administration begins with a loading dose of 1 mg/kg on day one, followed by a daily maintenance dose of 0.2 mg/kg, adjusted as needed based on plasma drug concentration after four weeks.
Explorer8 Trial: Design and Results
The FDA’s expanded approval is based on results from the pivotal Phase III explorer8 study (NCT04082429), which evaluated the safety and efficacy of Alhemo in 156 male patients aged 12 and older with severe HA or moderate‑to‑severe HB without inhibitors.
Participants were divided into two treatment arms: Arm 1 was no prophylaxis (on-demand factor replacement therapy), and Arm 2 was Alhemo prophylaxis. Randomization was in a 1:2 ratio, stratified by hemophilia type and prior bleed frequency. Additional groups included patients from earlier trials.
Key findings showed an 86% reduction in ABR for Hemophilia A and 79% for Hemophilia B. Average and median ABR values underscored this benefit: in hemophilia B, mean and median ABRs dropped to 3.1 and 1.6, respectively, compared with 14.8 and 14.9 for patients without prophylaxis; in hemophilia A, mean and median ABRs fell to 2.7 and 2.9, compared with 19.3 and 19.6 in the control group.
Median treatment durations were 24.1 weeks for the no‑prophylaxis arm and 32.1 weeks for the Alhemo arm. The most common adverse events (≥5% of patients) were injection site reactions (7%) and headaches (7%).
These findings reinforce earlier trial evidence showing that targeting TFPI can meaningfully reduce bleeding rates in hemophilia patients regardless of inhibitor status.
Novo Nordisk notes that the once-daily subcutaneous delivery offers an alternative to the frequent intravenous infusions many patients endure. This could help address treatment fatigue, improve adherence, and reduce missed doses, factors that significantly affect bleed prevention.
“For people living with hemophilia, it is important to continually monitor and discuss bleed control with their healthcare professional,” said Dr Allison P. Wheeler, Scientific Director, Washington Center for Bleeding Disorders. “With today’s approval, more people now have a daily prophylaxis option that may help decrease their bleeding rates.”
