FDA Approves Fitusiran for Reducing Bleeds in Patients With Hemophilia A/B

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Fitusiran (Qfitlia; Sanofi) was approved by the FDA as a subcutaneous prophylaxis for patients with hemophilia A or B with or without factor VIII or IX inhibitors.¹ The interference RNA therapeutic demonstrated low bleed rates across patient subgroups with as few as 6 injections a year in the phase 3 trials submitted with the new drug application.

“Today’s approval of Qfitlia is significant for patients with hemophilia because it can be administered less frequently than other existing options,” Tanya Wroblewski, MD, deputy director of the Division of Non-Malignant Hematology in the FDA’s Center for Drug Evaluation and Research, said in a statement.¹ “This new treatment option highlights our continued efforts to improve the lives of patients with hemophilia.”

The ATLAS research is comprised of a series of trials that have yielded years of long-term, comprehensive data on safety and efficacy.

Data from the phase 3 ATLAS-A/B (NCT03417245) and ATLAS-INH (NCT03417102) studies showed significant reductions in annualized bleeding rates (ABR) with once-monthly subcutaneous fitusiran prophylaxis (80 mg) compared with on-demand clotting factor concentrates (CFCs) and bypassing agents (BPAs).² Across both studies, fitusiran prophylaxis achieved a 90% reduction in ABR (95% CI, 84.1-93.6; P < .0001), indicating a statistically significant and clinically meaningful improvement in bleeding episodes and quality of life.

In the ATLAS-INH study, 25 of 38 (66%) participants with inhibitors experienced zero bleeds with fitusiran, compared with just 1 of 19 (5%) in the on-demand BPA group. Similarly, the ATLAS-A/B study found that 40 of 79 (51%) participants without inhibitors receiving fitusiran experienced no bleeding episodes, compared with 2 of 40 (5%) in the on-demand CFC group.

The ATLAS OLE (NCT03754790) trial, a phase 3 open-label extension study that examined reduced dosing, demonstrated that an antithrombin-based dose regimen (AT-DR) effectively rebalanced hemostasis and enhanced thrombin generation in individuals with severe hemophilia A or B, with or without inhibitors.³ Adjusting from the original 80 mg monthly regimen, the optimized dosing strategy targeted antithrombin activity levels of 15% to 35%, reducing thrombotic risk.

Among 213 participants on AT-DR, with 78% receiving doses every 2 months, the treatment was well tolerated and significantly reduced bleeding episodes. Integrated efficacy analyses confirmed AT-DR’s superiority over on-demand CFCs and BPAs, achieving up to a 73% reduction in ABR while offering comparable protection to CFC prophylaxis. With as few as 6 injections per year, AT-DR presents a promising, less burdensome treatment option.

“Current treatment options can make people with hemophilia feel they need to choose between effective bleed control and convenient dosing schedules, leading to trade-offs when it comes to disease management," Phil Gattone
president and CEO, National Bleeding Disorders Foundation, said in a statement.⁴ "Qfitlia takes a novel approach to providing protection for people living with hemophilia while reducing the frequency of dosing for patients and their families.”

Common side effects are viral infection, common cold symptoms, and bacterial infection.

Fitusiran has a boxed warning for thrombotic events and gallbladder disease, as well as a warning about liver toxicity and the need to monitor liver blood tests at baseline and monthly for at least 6 months after initiating therapy.¹

The fitusiran approval comes just months after the FDA approved concizumab-mtci (Alhemo; Novo Nordisk) as the first subcutaneous prophylaxis for hemophilia A and B with inhibitors.⁵

Additional reporting by Laura Joszt, MA.

References

1. FDA approves novel treatment for hemophilia A or B, with or without factor inhibitors. FDA. News release. March 28, 2025. Accessed March 28, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-treatment-hemophilia-or-b-or-without-factor-inhibitors

2. Two fitusiran Phase 3 studies published in The Lancet and The Lancet Haematology highlight potential to address unmet needs across all types of hemophilia. News release. Sanofi. April 4, 2023. Accessed March 27, 2025. https://www.sanofi.com/en/media-room/press-releases/2023/2023-04-04-05-00-00-2640246

3. Young G, Kavakli K, Klamroth R, et al. Safety and efficacy of a fitusiran antithrombin-based dose regimen in people with hemophilia A or B: the ATLAS-OLE study. Blood. Published online March 7, 2025. doi:10.1182/blood.2024027008

4. Press release: Qfitlia approved as the first therapy in the US to treat hemophilia A or B with or without inhibitors. Sanofi. News release. March 28, 2025. Accessed March 28, 2025. https://www.sanofi.com/en/media-room/press-releases/2025/2025-03-28-20-07-38-3051637

5. Grossi G. First subcutaneous prophylaxis for hemophilia A and B with inhibitors approved by FDA. AJMC®. December 23, 2024. Accessed March 28, 2025. https://www.ajmc.com/view/first-subcutaneous-prophylaxis-for-hemophilia-a-and-b-with-inhibitors-approved-by-fda