FDA, ASH Experts Review Newly Approved Therapies in Hemophilia

Each year, the FDA approves a slew of new treatments for rare diseases. In rare hematologic conditions such as hemophilia A or B, the landscape of available treatment options has rapidly expanded in recent years, with major approvals in 2025 that stand to transform the treatment paradigm for patients with these diseases.

At the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, hematology experts and regulators from the FDA held a joint symposium to review new frontiers in rare hematology based on the novel drugs approved in 2025. A major theme of the discussion was the shift from replacement to reinvention, with many new therapies gradually moving away from factor replacement as a treatment for these hematologic conditions to more optimal alternatives.¹

A New Treatment Landscape in Hemophilia A and B

Fitusiran

Fitusiran (Qfitlia; Alnylam Pharmaceuticals, Sanofi), a first-in-class antithrombin-targeting small interfering RNA drug (siRNA), was approved by the FDA in March 2025. It is indicated for the prophylactic treatment of adult and pediatric patients aged 12 years and older with hemophilia A or B regardless of their inhibitor status. As a non-factor replacement therapy, it inhibits natural anti-coagulants to increase thrombin generation.^1,2

During the session, Alison Moliterno, MD, a medical officer in the division of nonmalignant hematology at the FDA, explained the efficacy and safety data behind fitusiran’s approval.

Efficacy and Safety

In the landmark ATLAS constellation of studies, which featured males with severe hemophilia A or B with or without inhibitor use, fitusiran was found to be more effective at than on-demand treatment with factor concentrates at reducing mean annualized bleeding rate (ABR). Importantly, efficacy in these trials was reported in patients with and without inhibitor use. Moliterno explained that initial thrombotic adverse events led to a dosing modification, allowing for a range of maintained anti-thrombin activity between 15% and 35% based on a patient’s individual circumstances, rather than a flat dose.¹

A boxed warning is featured on the product for acute and recurrent gallbladder disease, along with the risk of thrombosis. The warnings are intended to make prescribers aware of these risks so they can make a better decision about whether fitusiran is right for their patient and so signs and symptoms can be identified early on in treatment. Despite these warnings, Moliterno emphasized the transformative potential of fitusiran in patients with hemophilia.¹

“Fitusiran represents a new therapeutic option for patients with hemophilia with or without inhibitors and expands the treatment landscape for hemophilia,” Moliterno said in her conclusion.¹

Concizumab

Concizumab (Alhemo; Novo Nordisk) is a subcutaneous, anti-tissue factor pathway inhibitor (TFPI) antagonist. The humanized monoclonal antibody blocks TFPI, which leads to thrombin generation independent of the intrinsic pathway. It was first approved by the FDA in December 2024 for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients aged 12 and older with hemophilia A or hemophilia B with inhibitors. Its indication later expanded to include patients with hemophilia A or B without inhibitor use.^1,3,4

Andrew Dmytrijuk, MD, a senior medical reviewer in the division of nonmalignant hematology at the FDA, provided an overview of concizumab’s efficacy and safety, primarily derived from the Explorer7 (NCT04083781) and Explorer8 (NCT04082429) clinical trials.¹

Efficacy and Safety

Each respective Explorer trial evaluated the efficacy and safety of concizumab in patients with hemophilia A and B. Explorer7 primarily evaluated patients who rely on inhibitors. In the trial, 133 patients were randomized to receive no prophylaxis or concizumab prophylaxis, with efficacy determined through comparing the number of treated bleeding episodes between each group. Dmytrijuk reported an 86% reduction in treated spontaneous and traumatic bleeding episodes with concizumab use.^1,3

In Explorer8, investigators randomized patients from a noninhibitor population. In total, 148 were randomized to receive either concizumab or on-demand treatment. A statistically meaningful reduction in annualized bleeding rate of 79% for patients with hemophilia B and 86% for patients with hemophilia A was observed.^1,4

Dymtrijuk highlighted the low risk of thromboembolic events reported among patients treated with concizumab. He noted that events were reported in only 1.9% of patients and “occurred in patients with multiple risk factors for thromboembolism, including the use of high doses for prolonged treatment with factor product and aging.” The robust efficacy shown in the clinical trials for concizumab allowed Dymtrijuk and his FDA colleagues to deem the product “an important addition to available treatment regimens for patients with hemophilia A or B with or without inhibitors.”¹

Clinical Considerations

With these new options now available for patients with hemophilia, many patients may feel motivated to alter their treatment regimens and switch from traditional factor replacement to a less burdensome and possibly more effective alternative. Anjali Sharathkumar, MBBS, MD, MS, professor of pediatrics at the University of Iowa, discussed the key clinical considerations for health care providers regarding fitusiran and concizumab for their practices.¹

Above all else, Sharathkumar expressed gratitude for the myriad new treatment options available and underscored the profound change that these treatments represent for patients. Overall, they represent a major paradigm shift away from traditional factor replacement and instead focus on thrombin generation.¹

“As someone who was trained in a place where prior options were our only choice, I feel very overwhelmed and grateful that our patients will now have so many treatment options,” Sharathkumar said during the session.¹

A major consideration that Sharathkumar cautioned was recognizing that changing treatments from factor replacement to non-factor replacement “is not just a product switch, but a hemostatic switch” that moves a patient’s coagulation balance towards a tendency for thrombosis. Each product contains their own trade-offs and considerations that patients and clinicians must consider. For example, Sharathkumar cited the very good bleed control and improved adherence with concizumab and fitusiran but noted that there are risks worth keeping in mind that are not associated with traditional factor replacement, such as thrombosis, liver toxicity, and reactions with antidrug antibodies.¹

She also explained key candidate selection criteria that are important when considering these novel therapies. These include considering a patient’s goal, their activity levels, accompanying comorbidities, safety given a patient’s clinical presentation, and recognition of possible gaps in bleed control, such as breakthrough and perioperative bleeding. Sharathkumar explained that patients must be prepared for their “new normal,” which includes educating them on new lab monitoring, ensuring they monitor bleeds as usual, and describing signs of thrombosis. She also encouraged clinicians to set up a cadence where a patient calls them before every factor infusion.¹

“Ask 3 questions: Why are you switching the patient in the first place? How do I do this switch safely? And how do I prepare the patient for their ‘new normal’?” Sharathkumar explained. Ultimately, she cites the importance of continued shared decision-making between the patient and clinician to ensure successful outcomes with rebalancing therapies for hemophilia.¹

“I clearly think that rebalancing therapies are a game changer,” Sharathkumar concluded.¹

REFERENCES

1. Whyte-Stewart D, Moliterno A, Dmytrijuk A, et al. ASH-FDA joint symposium on newly approved therapies I: new frontiers in rare hematology – from replacement to reinvention. Presented: 67^th American Society of Hematology Annual Meeting and Exposition; December 8, 2025; Orlando, FL; Hyatt Regency Ballroom S. Accessed via ASH Virtual Platform December 8, 2025.

2. Halpern L. FDA approves fitusiran for prophylactic hemophilia A, B treatment regardless of inhibitor status. Pharmacy Times. Published March 28, 2025. Accessed December 8, 2025. https://www.pharmacytimes.com/view/fda-approves-fitusiran-for-prophylactic-hemophilia-a-b-treatment-regardless-of-inhibitor-status

3. Gerlach A. FDA approves concizumab-mtci to prevent, reduce bleeding in patients with hemophilia A or B. Pharmacy Times. Published December 23, 2024. Accessed December 8, 2025. https://www.pharmacytimes.com/view/fda-approves-concizumab-mtci-to-prevent-reduce-bleeding-in-patients-with-hemophilia-a-or-b

4. Halpern L. FDA expands approval of concizumab-mtci to include hemophilia A, B without inhibitor use. Pharmacy Times. Published August 1, 2025. Accessed December 8, 2025. https://www.pharmacytimes.com/view/fda-expands-approval-of-concizumab-mtci-to-include-hemophilia-a-b-without-inhibitor-use