Efanesoctocog Alfa Shows Promise for Severe Hemophilia A Therapy

Replacement with factor VIII concentrates remains the standard of care for hemophilia A but requires frequent infusions and imposes a significant therapy burden. Efforts to extend factor VIII half-life though factor VIII modification are under way to reduce the therapy burden.

Researchers evaluated the safety, efficacy, and pharmacokinetics of efanesoctocog alfa, an investigational molecule composed of recombinant factor VIII protein with additional modifications — a von Willebrand D'D3 fragment and Fc portion of IgG — that extend its half-life up to 5 days. In the multinational, open-label, phase 3 trial, previously treated patients with severe hemophilia A (≥150 factor VIII exposure days) ages 12 years and older received either once weekly prophylaxis with intravenous efanesoctocog alfa (50 IU per kg) for 52 weeks (group A, n=133) or on-demand efanesoctocog alfa for 26 weeks followed by once-weekly prophylaxis for 26 weeks (group B, n= 26).

The mean annualized bleeding rate (ABR) in group A — the primary endpoint — was 0.71. Patients in group A had a significant reduction in mean ABR from 2.96 pre-study to 0.69 post-study. The median ABR was 0 (interquartile range, 0 to 1.04). There were 362 bleeding episodes, most in group B, and 97% resolved with one dose of efanesoctocog alfa. With weekly prophylaxis, mean factor VIII activity was >40 IU/dL for roughly 4 days and was 15 IU/dL at day 7.

Patients in group A also experienced significantly improved physical health, pain intensity, and joint health. In the overall study population, efanesoctocog alfa had an acceptable side-effect profile, and no patients developed factor VIII inhibitors.