Efanesoctocog Alfa prevents bleeding and improves QoL in patients with severe Hemophilia A: NEJM

The treatment improved joint health, pain and physical health and provided normal to near-normal factor VIII activity.

Efanesoctocog alfa is known to provide high sustained factor VIII activity through overcoming the von Willebrand factor–imposed half-life ceiling. There is no clarity on the safety, efficacy, and pharmacokinetics of efanesoctocog alfa for treating and preventing bleeding episodes in previously treated patients with severe hemophilia A.

Annette von Drygalski, University of California in San Diego, and associates conducted a phase 3 study comprising patients with severe hemophilia A aged 12 and older. In group A, patients were assigned to once-weekly prophylaxis with efanesoctocog alfa for 52 weeks, 50 IU per kilogram of body weight. In group B, patients received on-demand efanesoctocog alfa treatment for 26 weeks, followed by once-weekly prophylaxis with efanesoctocog alfa for 26 weeks.

In group A, the mean annualized bleeding rate was determined (primary endpoint); an intrapatient comparison was made between the annualized bleeding rate during prophylaxis in group A and the rate during prestudy factor VIII prophylaxis (key secondary endpoint). Additional endpoints included safety, bleeding episodes, pharmacokinetics, changes in pain, joint health, and physical health.

The researchers reported the following findings:

• In group A comprising 133 patients, the median annualized bleeding rate was 0, and the estimated mean annualized bleeding rate was 0.71.
• There was a reduction in the mean annualized bleeding rate from 2.96 to 0.69, a finding that showed superiority over prestudy factor VIII prophylaxis.
• Group B comprised a total of 26 patients. One injection of efanesoctocog alfa in the overall population nearly resolved all bleeding episodes (97%).
• Efanesoctocog alfa's weekly prophylaxis provided mean factor VIII activity of above 40 IU per deciliter for most of the week and 15 IU per deciliter on day 7.
• Fifty-two weeks of prophylaxis with efanesoctocog alfa (group A) improved physical health, pain intensity, and joint health.
• Efanesoctocog alfa showed an acceptable side-effect profile in the overall study population, and there was no detection of the development of inhibitors to factor VIII.

"Our findings show that once-weekly efanesoctocog alfa, through maintaining high sustained factor VIII activity, provided substantial improvements in quality of life and clinical outcomes for patients with severe hemophilia A," the researchers conclude.

Reference:

Annette von Drygalski et al, Efanesoctocog Alfa Prophylaxis for Patients with Severe Hemophilia A, New England Journal of Medicine (2023). DOI: 10.1056/NEJMoa2209226