FDA approves concizumab-mtci for hemophilia A/B without inhibitors in patients 12 years and older

On July 31, 2025, the FDA approved concizumab-mtci (Alhemo; Novo Nordisk) injection as a once-daily prophylactic treatment to prevent or reduce bleeding episodes in patients 12 years and older with hemophilia A or B (HA/HB) without inhibitors, according to an announcement from Novo Nordisk. The approval is based on results from the phase 3 explorer8 trial and extends the previous December 2024 approval of the therapy for use in patients with inhibitors.

Many patients with HA or HB without inhibitors currently receive intravenous prophylactic therapies. The new approval offers a subcutaneous injection alternative in the form of a prefilled pen. According to the company, concizumab-mtci is the first subcutaneous injectable pen option of its kind for patients with or without inhibitors.

“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 Anna Windle, PhD, senior vice president, clinical development, medical and regulatory affairs, Novo Nordisk. “By building on the initial indication for Alhemo for those with hemophilia with inhibitors—an especially significant development in hemophilia B where challenges still exist despite advanced treatment options—Novo Nordisk continues its 35+ year legacy in rare bleeding disorders to continue to help address the unmet needs of this community.”

Concizumab-mtci is a tissue factor pathway inhibitor (TFPI) antagonist. It improves thrombin generation by inhibiting TFPI, thereby supporting blood clot formation in patients with hemophilia regardless of inhibitor status.

“For people living with hemophilia, it is important to continually monitor and discuss bleed control with their health care professional,” said Allison P. Wheeler, MD, scientific director, Washington Center for Bleeding Disorders, Seattle, Washington. “With today’s approval of Alhemo for hemophilia A or B without inhibitors, more people living with these rare blood disorders now have a daily prophylaxis option that may help decrease their bleeding rates.”

The FDA decision is based on data from the phase 3 explorer8 trial, which enrolled 156 males 12 years and older with hemophilia A or B without inhibitors. Participants were randomly assigned 1:2 to receive either no prophylaxis (on-demand factor VIII or IX replacement) or concizumab-mtci prophylaxis. The primary outcome measured was the annualized bleeding rate (ABR).

The explorer8 trial evaluated patients over a median duration of 24.1 weeks in the no-prophylaxis group and 32.1 weeks in the concizumab-mtci group. Efficacy was assessed separately for patients with hemophilia A and B after all participants completed their respective treatment periods.

For patients with hemophilia B, concizumab-mtci reduced ABR by 79% compared with no prophylaxis (ABR ratio: 0.21; 95% CI: 0.10-0.45; P <.0001). For patients with hemophilia A, ABR was reduced by 86% (ABR ratio: 0.14; 95% CI: 0.07-0.29; P <.0001). Average ABR among patients with HB receiving concizumab-mtci was 3.1 (range: 1.9-5.0), compared with 14.8 (8.1-26.9) in those not receiving prophylaxis. Median ABR was 1.6 (0.0-4.8) vs 14.9 (3.3-22.1), respectively. In patients with HA, average ABR was 2.7 (1.6-4.6) for the treatment group and 19.3 (11.3-33.0) for controls. Median ABR was 2.9 (0.0-5.2) vs 19.6 (17.3-30.4), respectively.

The most common adverse reactions reported in 5% or more of patients treated with concizumab-mtci were injection site reactions and headache, each occurring in 7% of participants.

The concizumab-mtci pen is offered in prefilled, premixed formulations of 60 mg/1.5 mL, 150 mg/1.5 mL, and 300 mg/3 mL, administered via 32-gauge, 4-mm subcutaneous needles. The treatment is initiated with a loading dose of 1 mg/kg followed by daily maintenance dosing of 0.2 mg/kg, with potential adjustments based on plasma concentration levels measured after 4 weeks.

Concizumab-mtci is not indicated for individuals younger than 12 years or for those undergoing immune tolerance induction therapy. The therapy is not known to induce or enhance the development of direct inhibitors to factor VIII or IX.

With this expanded indication, concizumab-mtci may offer an additional option for prophylaxis and individualized management for patients living with hemophilia A or B, regardless of inhibitor status.

Reference:

FDA approves Alhemo as once-daily prophylactic treatment to prevent or reduce the frequency of bleeding episodes for adults and children 12 years of age and older with hemophilia A or B (HA/HB) without inhibitors. News release. Novo Nordisk. July 31, 2025. Accessed July 31, 2025. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=916409