Fitusiran reviewed for hemophilia A, B, with or without inhibitors

Sanofi's Altuviiio, fitusiran results were presented at recent ISTH congress

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Note: This article was updated June 26, 2024, to clarify that the analysis of fitusiran in surgery was conducted in patients receiving prophylactic treatment with the therapy.

The U.S. Food and Drug Administration (FDA) is reviewing a request to approve fitusiran, an under-the-skin injection therapy, as a treatment for adults and adolescents with hemophilia A or hemophilia B, with or without inhibitors.

A decision is expected by March 28, 2025, according to fitusiran’s developer Sanofi.

“We look forward to working in partnership with regulatory agencies to keep bringing novel options to those living with hemophilia,” Dietmar Berger, MD, PhD, chief medical officer and global head of development at Sanofi, said in a company press release. Fitusiran also is being considered in China and Brazil.

Hemophilia is caused by deficiencies in proteins that help blood to clot, specifically clotting factor VIII (FVIII) in hemophilia A and factor IX (FIX) in hemophilia B.

Standard treatment involves replacement therapies, wherein a version of the missing protein is administered to maintain clotting factor levels high enough to prevent and control bleeding episodes. But some patients may develop neutralizing antibodies, called inhibitors, that target the delivered clotting factor, preventing it from working as intended and reducing replacement therapies’ effectiveness.

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Switch to Fitusiran Reduced Bleed Rates in Hem A and B

Fitusiran’s use in 60 surgeries analyzed

Fitusiran is designed to lower levels of the protein antithrombin, which normally acts as a quality-control mechanism to prevent unnecessary clotting. By reducing antithrombin, the therapy should reduce bleeding risk in people with hemophilia, regardless of the type they have or the presence of inhibitors.

The therapy has been tested in hemophilia patients in half a dozen Phase 3 clinical trials, all part of the ATLAS clinical development program. Some are still ongoing and Sanofi recently shared new clinical data at this year’s congress of the International Society on Thrombosis and Haemostasis (ISTH) in Bangkok.

Using ATLAS data, researchers analyzed patient outcomes in terms of bleed management in major surgeries while on fitusiran prophylaxis. The results were shared in the presentation “Surgical experience in people with hemophilia A or B with and without inhibitors receiving fitusiran.”

The analysis included data from 60 major surgeries performed as part of fitusiran’s clinical development program up until June 2023. Most had followed bleed management guidelines and nearly half were conducted in patients with inhibitors.

No notable safety concerns were seen and fitusiran’s effectiveness at controlling blood loss was rated as excellent in more than 90% of the operations. Outcomes were slightly less favorable when surgeons didn’t follow proper bleed management guidelines, said the researchers, who emphasized their importance for hemophilia patients.

The researchers said “major surgeries can be safely and effectively conducted during fitusiran prophylaxis when BMG [bleed management guidelines] are followed, irrespective of inhibitor status.”

Analyzing Altuviiio

In another presentation at ISTH, Sanofi showcased new data from the Phase 3 XTEND-ed extension study (NCT04644575), which is monitoring the long-term outcomes of people with hemophilia A given prophylactic (preventive) once-weekly treatment with the approved replacement therapy Altuviiio (efanesoctocog alfa).

The study’s main arm enrolled people with hemophilia A who’d participated in previous Altuviiio trials, including the Phase 3 XTEND-1 trial (NCT04161495) and the Phase 3 XTEND-Kids trial (NCT04759131).

Interim data from adults and adolescents who participated in XTEND-1 before enrolling in XTEND-ed were shared in “First Interim Analysis of Clinical Outcomes in Adults and Adolescents With Severe Hemophilia A Receiving Efanesoctocog Alfa Prophylaxis in XTEND-ed, a Phase 3 Long-term Extension Study.” Interim data from children younger than 12 who participated in XTEND-Kids were detailed in “Long-term Outcomes With Efanesoctocog Alfa Prophylaxis for Previously Treated Children With Severe Hemophilia A, an Interim Analysis of the Phase 3 XTEND-ed Study.

Results from adults and adolescents showed the mean annualized bleed rate was 0.72 bleeds per year for patients who received preventive treatment with Altuviiio in XTEND-1 and 0.42 bleeds a year for those who had received on-demand treatment with Altuviiio, followed by a preventive regimen in XTEND-1.

Interim data from children younger than 12 were similar, with a mean annualized bleed rate of 0.7 bleeds a year. Across patients of all ages, none developed inhibitors, and no new safety issues were noted.

In the separate presentation “Interim Analysis of Joint Outcomes in Adult and Adolescent Patients with Severe Hemophilia A Receiving Efanesoctocog Alfa During the Phase 3 XTEND-ed Long-Term Extension Study,” researchers analyzed measures of joint health in XTEND-ed. Across various measures used, scores were either unchanged (stable) or improved after patients received treatment for a year in the extension study, results that indicate “once-weekly prophylaxis with [Altuviiio] is associated with improvement or maintenance of joint health in adults and adolescents.”

A fourth presentation titled “Perioperative Management with Efanesoctocog Alfa in Adults, Adolescents, and Children with Severe Hemophilia A in the Phase 3 XTEND Clinical Program,” detailed the outcomes of 49 major surgeries in 41 patients where Altuviiio was used for bleed control in XTEND-ed and earlier trials. The therapy’s efficacy was rated as excellent in 43 of the procedures.

“These data reinforce why it’s critical to have treatment options like Altuviiio and fitusiran that deliver effective outcomes in multiple scenarios and that can be used throughout a person’s life,” Berger said.