FDA Approves First-in-Class Factor VIII Therapy for Hemophilia A

The US Food and Drug Administration (FDA) has approved once-weekly antihemophilic factor (Recombinant), Fc-VWF-XTEN Fusion Protein-ehtl (ALTUVIIIO™), a first-in-class, high sustained factor VIII replacement therapy for adults and children with hemophilia A.¹

Co-developed by Sanofi and Sobi, the therapy is the first-and-only treatment that delivers normal to near-normal factor activity levels and significant reductions in bleeds with once-weekly dosing, according to the news release.

“This approval marks an important clinical advancement for the hemophilia community because we have an option that can achieve higher levels of factor activity with a single simplified weekly dose,” said Lynn Malec, MD, Medical Director of Comprehensive Center for Bleeding Disorders and Associate Investigator at The Versiti Blood Research Institute in the release. “By maintaining high levels of factor activity throughout the week, patients can be confident in the bleed protection ALTUVIIIO offers.”

Previously referred to as efanesoctocog alfa, the therapy is indicated for routine prophylaxis and on-demand treatment to control bleeding episodes, as well as perioperative management for adults and children with hemophilia A. Its FDA approval was based on recently published data from the pivotal XTEND-1 phase 3 study.

Results from the study suggest once-weekly therapy prophylaxis met the primary endpoint and provided significant bleed protection for people with severe hemophilia A. Data showed a mean annual bleeding rate of 0.70 (95% confidence interval [CI], 0.5 - 1.0) and a median rate of 0.0.

In addition, the therapy met the key second endpoint with a significant reduction of 77% in annual bleeding rate versus prior factor prophylaxis based on an intra-patient comparison (95% CI, 58% - 87%) and prevention of joint bleeds. The release cited treatment provided 100% resolution of target joints and mean factor VIII activity greater than 40% for most of the week and greater than 10% at Day 7.

The study results additionally indicate the agent was well-tolerated and inhibitor development to factor VIII was not detected, although the release noted it is possible following administration of the therapy.

Interim data from the ongoing XTEND-Kids trial showed that children younger than 12 years receiving once-weekly therapy for 26 weeks (n = 23) experienced a mean annual bleeding rate of 0.5 (95% CI, 0.2 - 1.3) and a median rate of 0. Full results are anticipated at a future medical meeting, according to the company.

In the release, Paul Hudson, CEO of Sanofi, noted the therapy’s approval may allow patients and physicians to rethink living with hemophilia.

“The high sustained factor activity levels that can be achieved with ALTUVIIIO have the potential to change the hemophilia landscape,” Hudson said. “For the first time, with a once-weekly dose, powerful bleed protection is a reality for patients.”

The application for the therapy was evaluated by the FDA under Priority Review and it was previously granted Breakthrough Therapy designation in May 2022, Fast Track designation in February 2021, and Orphan Drug designation in August 2017.

References

1. FDA approves once-weekly ALTUVIIIO™, a new class of factor VIII therapy for hemophilia A that offers significant bleed protection. Sanofi Press room. https://www.news.sanofi.us/2023-02-23-FDA-approves-once-weekly-ALTUVIIIO-TM-,-a-new-class-of-factor-VIII-therapy-for-hemophilia-A-that-offers-significant-bleed-protection. Published February 23, 2023.