Efanesoctocog alfa — an agent that provides high sustained factor VIII activity by overcoming the von Willebrand factor–imposed half-life ceiling — provided clear clinical benefits in a phase 3 trial. Bleeding prevention was improved over prophylactic factor VIII regimens used before the study. Once-weekly doses resulted in normal to near-normal factor VIII activity and improvements in physical health, pain, and joint health.
The study assessed the efficacy, safety, and pharmacokinetics of efanesoctocog alfa for prophylaxis and treatment of bleeding episodes in previously treated patients 12 years of age or older with severe hemophilia A. Patients in group A received regularly scheduled doses of efanesoctocog alfa 50 IU/kg once weekly for 52 weeks. Those in group B received on-demand efanesoctocog alfa for 26 weeks, followed by once-weekly prophylaxis with efanesoctocog alfa for 26 weeks.
Based on a primary endpoint of the mean annualized bleeding rate in group A, the investigators found: “In group A (133 patients), the median annualized bleeding rate was 0 (interquartile range, 0 to 1.04), and the estimated mean annualized bleeding rate was 0.71 (95% confidence interval [CI], 0.52 to 0.97). The mean annualized bleeding rate decreased from 2.96 (95% CI, 2.00 to 4.37) to 0.69 (95% CI, 0.43 to 1.11), a finding that showed superiority over prestudy factor VIII prophylaxis (P <0.001). A total of 26 patients were enrolled in group B. In the overall population, nearly all bleeding episodes (97%) resolved with one injection of efanesoctocog alfa. Weekly prophylaxis with efanesoctocog alfa provided mean factor VIII activity of more than 40 IU per deciliter for the majority of the week and of 15 IU per deciliter at day 7. Prophylaxis with efanesoctocog alfa for 52 weeks (group A) improved physical health (P <0.001), pain intensity (P = 0.03), and joint health (P = 0.01). In the overall study population, efanesoctocog alfa had an acceptable side-effect profile, and the development of inhibitors to factor VIII was not detected.”
Editorial: “A major advantage of efanesoctocog alfa over the currently available factor VIII mimetic therapy and the hemostatic rebalancing therapies that are still being evaluated in clinical trials is its value as a true factor VIII replacement that can be used to treat acute bleeding and can be measured by standard laboratory assays to allow for monitoring and dose adjustments when needed,” writes an editorialist. “In addition, when efanesoctocog alfa is given once weekly, near-normal factor VIII levels can persist for approximately 4 days. Although trials of factor VIII gene therapy are showing prolonged production of factor VIII, results to date suggest that factor VIII production in most patients gradually declines over the course of a few years to levels similar to the trough levels seen with weekly efanesoctocog alfa. In a crowded field of transformative therapies for hemophilia, efanesoctocog alfa stands out as a winner — a major therapeutic advance that achieves highly protective factor VIII levels with a once-weekly infusion.”