FDA Approves Concizumab for Hemophilia A or B with Inhibitors

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has approved concizumab-mtci (Alhemo) injection as a once-daily prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children aged ≥12 years with hemophilia A or B with inhibitors.¹

Announced by Novo Nordisk, on December 20, 2024, concizumab is a tissue factor pathway inhibitor (TFPI) antagonist dosed in a prefilled, premixed pen for subcutaneous injection, rather than an intravenous infusion, marking it a first-of-its-kind treatment for hemophilia A or B with inhibitors.

“The approval of [concizumab] – a first-of-its-kind, prophylaxis, subcutaneous injection pen for adults and children 12 years and older with hemophilia A and B with inhibitors — provides a much-needed alternative to the current standard of care in hemophilia B with inhibitors, while offering patients with hemophilia A with inhibitors more treatment options, ultimately providing more patients with inhibitors the opportunity to personalize their care and address current treatment gaps,” Amy Shapiro, MD, chief executive officer and co-medical director at the Indiana Hemophilia & Thrombosis Center, Inc., said in a statement.¹

Regulatory approval was awarded based on positive results from the pivotal Phase 3 explorer7 trial, assessing the efficacy and safety of concizumab for the prevention of daily bleeds in the adult and pediatric populations living with hemophilia A or B with inhibitors. The trial’s primary objective was the number of treated spontaneous and traumatic bleeding episodes measured by the annual bleeding rate (ABR).

Reported results revealed an 86% reduction in ABR in patients randomized to concizumab prophylaxis, compared with no prophylaxis (ABR ratio, 0.14; 95% CI, 0.07 - 0.29; P <.001). Among those on concizumab prophylaxis, the estimated mean ABR was 1.7, compared with 11.8 for those without prophylaxis.

The overall mean ABR was identified as 0 for treated spontaneous and traumatic bleeds, compared with 9.8 ABR in patients with no prophylaxis. A secondary efficacy endpoint showed 64% of patients randomized to concizumab prophylaxis experienced no treated spontaneous and traumatic bleeds in the first 24 weeks versus 11% with no prophylaxis.

Safety outcomes reported the most common adverse reactions (≥5%) after concizumab prophylaxis were injection site reactions (18%) and uriticaria (6%). Serious adverse reactions observed in the trial were renal infarct and hypersensitivity reactions.

Approximately 30% of the population living with severe hemophilia A and 5–10% of those with severe hemophilia A develop inhibitors, challenging the treatment potential.² Therapies often improve the lives of patients with hemophilia, but those with hemophilia B with inhibitors continue to experience a burden given the relative lack of prophylactic options to prevent bleeding.

Designed to block TFPI, concizumab improves thrombin production when other clotting factors are missing or deficient in the presence of inhibitors. Given these unmet needs in hemophilia B with inhibitors, the FDA initially granted Breakthrough Therapy designation for concizumab in hemophilia B with inhibitors.³

“The approval of [concizumab] signifies a remarkable achievement in prophylactic hemophilia treatment for individuals with inhibitors aged 12 years and older who, in some cases, currently have few options,” Anna Windle, senior vice president of clinical development at Novo Nordisk, said in a statement.¹ “As the first treatment of its kind for this population, [concizumab] represents a significant step in helping to address the unmet needs to patients with hemophilia with inhibitors, highlighting Novo Nordisk’s commitment to patient-centric innovations in rare diseases.”

References

1. _{FDA approves Alhemo® injection 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 with inhibitors. Novo Nordisk. December 20, 2024. Accessed December 23, 2024. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=915084.}
2. _{Meeks SL, Batsuli G. Hemophilia and inhibitors: current treatment options and potential new therapeutic approaches. Hematology Am Soc Hematol Educ Program. 2016;2016(1):657-662. doi:10.1182/asheducation-2016.1.657}
3. _{Center for Drug Evaluation and Research. FDA approves drug for patients with hemophilia A or hemophilia B. U.S. Food and Drug Administration. December 20, 2024. Accessed December 23, 2024. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-prevent-or-reduce-frequency-bleeding-episodes-patients-hemophilia-inhibitors-or.}