The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for efanesoctocog alfa (BIVV001) for the treatment of hemophilia A.

Efanesoctocog alfa is a novel recombinant factor VIII (FVIII) therapy designed to extend protection from bleeds by breaking the von Willebrand factor ceiling, which imposes a half-life limitation on current FVIII treatments.

The multicenter, open-label, nonrandomized, interventional XTEND-1 study (ClinicalTrials.gov Identifier: NCT04161495) evaluated the efficacy and safety of efanesoctocog alfa in 159 patients 12 years of age and older with severe hemophilia A previously treated with factor VIII replacement therapy.

The study included 2 parallel treatment arms: the prophylaxis Arm A (n=133), where patients received a weekly prophylactic 50 IU/kg dose of efanesoctocog alfa intravenously (IV) for 52 weeks; and the on-demand Arm B (n=26), where patients received a weekly on-demand 50 IU/kg dose of efanesoctocog alfa IV for 26 weeks followed by weekly prophylaxis for 26 weeks.

The primary endpoint was the annualized bleeding rate (ABR) in Arm A. The key secondary endpoint was the intra-patient comparison of ABR during the efanesoctocog alfa weekly prophylaxis treatment period vs the historical prophylaxis ABR for some of the patients in Arm A who participated in a prior observational study using currently marketed factor VIII replacement therapies.

Results showed that weekly prophylactic treatment with efanesoctocog alfa resulted in clinically meaningful prevention of bleeds over 52 weeks; the median ABR was 0 with a mean ABR of 0.71. Moreover, once-weekly efanesoctocog alfa was found to be superior to prior prophylactic FVIII replacement therapy, demonstrating a statistically significant reduction in ABR based on intra-patient comparison (P <.001). 

Findings also showed that 96.7% of bleeds resolved with 1 injection of efanesoctocog alfa, with 94.9% of responses rated as excellent or good. Significant improvements in physical health (P =.0001), pain (P =.0276), and joint health (P =.0101) were also associated with efanesoctocog alfa prophylaxis. The most common treatment-emergent adverse events reported were headache, arthralgia, fall, and back pain.

“The results from the pivotal XTEND-1 phase 3 study demonstrate efanesoctocog alfa’s ability to reduce annualized bleeding rates, which supports its potential as a therapy with best-in-disease efficacy,” said Dietmar Berger, MD, PhD Global Head of Development and Chief Medical Officer at Sanofi.

The FDA is expected to make a decision on the application on February 28, 2023.

References

  1. Press Release: FDA grants priority review to efanesoctocog alfa for people with hemophilia A. News release. Sanofi – Aventis Groupe. Accessed August 30, 2022. https://www.globenewswire.com/news-release/2022/08/30/2506359/0/en/Press-Release-FDA-grants-priority-review-to-efanesoctocog-alfa-for-people-with-hemophilia-A.html
  2. von Drygalski A, Chowdary P, Kulkarni R, et al. Efficacy, safety, and pharmacokinetics of once-weekly efanesoctocog alfa (BIVV001) prophylaxis in previously treated patients with severe hemophilia A: results from the phase 3 XTEND-1 study. International Society on Thrombosis and Haemostasis 2022 Virtual Congress [abstract LB 01.4]. Accessed August 30, 2022.