Sanofi and Sobi Announce Positive Topline Results from Pivotal Phase 3 Trial of Efanesoctocog Alfa in Severe Hemophilia A

On March 10, Sanofi and Sobi jointly announced that efanesoctocog alfa (BIVV001), a long-acting hemophilia A therapy co-developed by the two companies, achieved positive topline results in a pivotal Phase 3 clinical trial for treating severe hemophilia A patients aged 12 and above. The study met its primary endpoint, demonstrating clinically meaningful reduction in bleeding among severe hemophilia A patients receiving once-weekly preventive treatment with efanesoctocog alfa. Additionally, compared with previous preventive treatments using Factor VIII (FVIII), efanesoctocog alfa showed superiority in preventing bleeding.

Hemophilia A is a hereditary disease caused by mutations in the gene encoding FVIII, resulting in the absence of FVIII. The current common treatment for hemophilia A is regular infusion of FVIII; however, patients typically require 3-4 infusions per week, causing significant inconvenience to their lives.

The half-life of natural FVIII in the blood is only about 12 hours because it forms a complex by binding with von Willebrand factor (VWF) in the blood. Although the binding of VWF enhances the stability of FVIII in the blood, the degradation rate of VWF itself also sets an upper limit on the retention time of FVIII in the blood, as FVIII bound to VWF is simultaneously degraded when VWF is broken down.

BIVV001 is designed to link FVIII with a VWF fragment, forming a complex that does not bind with natural VWF in the blood, thereby overcoming the half-life ceiling set by VWF. It aims to enable hemophilia A patients to achieve near-normal FVIII activity levels for most of the week following a single injection.

▲Schematic diagram of BIVV001 (Image source: Reference [2])

This open-label, non-randomized Phase 3 clinical trial was conducted in 159 patients aged 12 years and older with severe hemophilia A who had previously received factor VIII replacement therapy. The trial results showed that in patients receiving once-weekly preventive treatment with efanesoctocog alfa, the median annualized bleeding rate (ABR) over 52 weeks was 0, with a mean ABR of 0.71. In terms of safety, efanesoctocog alfa was well-tolerated, with no inhibitors against factor VIII detected. The most common treatment-emergent adverse events were headache, arthralgia, falls, and back pain.

References:

[1] Efanesoctocog alfa met primary and key secondary endpoints in pivotal study in hemophilia A, demonstrating superiority to prior factor prophylaxis treatment. Retrieved March 9, 2022, from https://www.globenewswire.com/news-release/2022/03/09/2399557/0/en/Efanesoctocog-alfa-met-primary-and-key-secondary-endpoints-in-pivotal-study-in-hemophilia-A-demonstrating-superiority-to-prior-factor-prophylaxis-treatment.html

[2] Konkle et al., (2020). BIVV001 Fusion Protein as Factor VIII Replacement Therapy for Hemophilia A. NEJM, DOI: 10.1056/NEJMoa2002699

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