FDA Expands Approval of Concizumab-mtci to Include Hemophilia A, B Without Inhibitor Use

The FDA has expanded the approval of once-daily concizumab-mtci (Alhemo; Novo Nordisk) injection to include patients aged 12 and older with hemophilia A or B (HA/HB) without inhibitors, allowing for prophylaxis to prevent or reduce the frequency of bleeding episodes in a larger hemophilia population. The approval, announced in a news release from Novo Nordisk, will reduce the burden for patients who do not use inhibitors and instead rely on intravenous replacement therapies.^1,2

Patients with hemophilia A or B who rely on inhibitors to manage their condition are in particular need of new treatment options. | Image Credit: © MercyTran - stock.adobe.com

"The FDA approval of an expanded indication for [concizumab] marks a meaningful step forward for people with hemophilia A or B without inhibitors who are looking for a new prophylaxis treatment option," Anna Windle, PhD, senior vice president of clinical development in medical and regulatory affairs at Novo Nordisk, said in the news release.¹

New Trial Results Indicate Reduced Bleeding Without Inhibitor Use

Results from the phase 3 explorer8 clinical (NCT04082429) trial bolstered concizumab towards its approval for the noninhibitor population. Through measuring annualized bleeding rate (ABR), the investigators of explorer8 aimed to compare the number of treated spontaneous and traumatic bleeding episodes in patients with HA/HB without inhibitors receiving concizumab prophylaxis versus no prophylaxis, in the form of on-demand factor VIII/factor IX treatment.^1,3

A total of 148 patients were randomly assigned to receive either concizumab or on-demand treatment. The authors observed a statistically meaningful reduction in ABR of 79% for patients with HB (ABR ratio: 0.21 [95% CI, 0.10–0.45]; P < .0001) and 86% for patients with HA (ABR ratio: 0.14 [95% CI, 0.07–0.29]; P < .0001).^1,3

Furthermore, there were notable reductions observed in average and median ABRs, which gave further credence to concizumab’s efficacy in this population. For patients with HB, the authors reported an average ABR of 3.1 and a median ABR of 1.6, compared with 14.8 and 14.9, respectively; and for patients with HA, there was an average ABR of 2.7 and a median ABR of 2.9 compared with 19.3 and 19.6, respectively.^1,3

Regarding safety, the most frequently observed adverse events in the trial were SARS-CoV-2 infection, an increase in fibrin D-dimers, and upper respiratory tract infection. In a positive development—and aligning with past research on concizumab—most adverse events were mild to moderate in nature, with an unlikely relation to concizumab treatment. Other common reports included those of injection site pain and headache, though these were manageable.^1,3

Concizumab Now Effective Option For Both Inhibitor and Non-Inhibitor Patients With Hemophilia A or B

Previously, concizumab was evaluated in the explorer7 clinical trial (NCT04083781), specifically for patients with HA using factor VIII inhibitors or HB using factor IX inhibitors. In the trial, patients receiving concizumab experienced a significant reduction in median ABR, with a positive safety profile. Based on these trial results, the FDA approved concizumab for patients with HA/HB who use inhibitors in December 2024.^1,2

The new indication will provide individuals who rely on intravenous infusions to manage their condition a novel subcutaneous option. Concizumab is provided as a prefilled, premixed pen for injection in either 60 mg/1.5 mL, 150 mg/1.5 mL, or 300 mg/3 mL doses through 32-gauge, 4 mm needles. Now, pharmacists will have an option that they can universally provide to patients with hemophilia, both with and without inhibitor use.¹

Concizumab is designed to inhibit the tissue factor pathway inhibitor, thereby heightening factor Xa production during coagulation. This improves thrombin generation and the formation of clots in patients with HA/HB with or without inhibitors. Importantly, concizumab’s therapeutic effects avoid influence from inhibitory antibodies of factor VIII or factor IX, ensuring that patients who may be transitioning treatments or still partly relying on infusions do not experience disruptions in care.¹

"For people living with hemophilia, it is important to continually monitor and discuss bleed control with their healthcare professional," Allison P. Wheeler, MD, scientific director of the Washington Center for Bleeding Disorders, said in the news release. “With today's approval of [concizumab] 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."¹

REFERENCES

1. Novo Nordisk. 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. PRNewswire. Published July 31, 2025. Accessed August 1, 2025. https://www.prnewswire.com/news-releases/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-hahb-without-inhibitors-302519177.html

2. Gerlach A. FDA Approves Concizumab-mtci to Prevent, Reduce Bleeding in Patients With Hemophilia A or B. PharmacyTimes. Published December 23, 2024. Accessed August 1, 2025. https://www.pharmacytimes.com/view/fda-approves-concizumab-mtci-to-prevent-reduce-bleeding-in-patients-with-hemophilia-a-or-b

3. Chowdary P, Angchaisuksiri P, Apte S, et al. Concizumab prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial. The Lancet Hematol. 2024;11(12):E891-E904. doi:10.1016/S2352-3026(24)00307-7