FDA approves once-weekly efanesoctocog alfa, a new class of high-sustained factor VIII therapy for haemophilia A.

Efanesoctocog alfa is the first and only haemophilia A treatment that provides patients with normal to near-normal factor VIII activity levels for a significant part of the week with once-weekly dosing, resulting in superior protection from bleeds compared to existing factor VIII prophylaxis.

Haemophilia A is a rare, genetic disorder in which the ability of a person's blood to clot is impaired due to a lack of factor VIII. Haemophilia A occurs in about one in 5,000 male births annually, and more rarely in females. People with haemophilia can experience bleeding episodes that can cause pain, irreversible joint damage and life-threatening haemorrhages. Despite advancements in treatment made in recent years, a large unmet medical need still exists and requires further improvement in the standard of care.

"This approval marks an important clinical advancement for the haemophilia community because we have an option that can achieve higher levels of factor activity with a single weekly dose," said Lynn Malec, MD, Medical Director of Comprehensive Center for Bleeding Disorders and Associate Investigator at Versiti Blood Research Institute, and Associate Professor of Medicine and Pediatrics at The Medical College of Wisconsin, US. "By maintaining high levels of factor activity throughout the week, patients can be confident in the bleed protection efanesoctocog alfa offers."

The FDA approval is primarily based on data from the pivotal XTEND-1 phase III study recently published in The New England Journal of Medicine ( previously cited). Once-weekly efanesoctocog alfa met the primary endpoint, providing significant improvements in bleed protection for people with severe haemophilia A with median and mean annualised bleeding rates (ABR) of 0.00 (interquartile range: 0.00-1.04) and 0.71 (95% confidence interval: 0.52-0.97), respectively. Efanesoctocog alfa met the key secondary endpoint with a significant reduction of 77% in ABR versus prior factor prophylaxis based on an intra-patient comparison. Efanesoctocog alfa prophylaxis with 50IU/kg/week provided mean factor VIII activity greater than 40% for the majority of the week with a trough activity of 15% on day seven, and these levels were associated with a low bleed risk.

Additional data showed prevention of joint bleeds with a median annualised joint bleeding rate of 0 (Q1, Q3: 0.0, 1.0). Treatment with efanesoctocog alfa provided 100% resolution of target joints, which are joints that have recurrent bleeds (e.g., knee, ankle, or elbow). In adults and adolescents, efanesoctocog alfa had a favourable safety profile and there were no signs of factor VIII inhibitor development..

Efanesoctocog alfa is expected to be commercially available in the US starting in the second quarter of 2023 and will be marketed as Altuviiio in Sanofi territories including the US.

Regulatory submission in the EU will follow the availability of final data from the XTEND-Kids paediatric study in the first half of 2023. The European Commission granted orphan designation in June 2019.