Weekly Efanesoctocog Alfa Improves Bleeding Prevention, Patient Health in Hemophilia A

Annette von Drygalski, MD, PharmD

According to recent research, once-weekly efanesoctocog alfa provided superior bleeding prevention to prestudy prophylaxis, normal to near-normal factor VIII activity, and improvements in physical health, pain, and joint health.

The phase 3 data suggested that efanesoctocog alfa may be a safe and effective treatment option for patients with severe hemophilia A, and could provide better outcomes than current treatment options.

Current treatment options for hemophilia A include prophylactic factor VIII replacement therapy to prevent bleeding episodes, or on-demand therapy, which is administered when bleeding occurs. Individuals with the rare genetic disorder lack the protein factor VIII, which is necessary for normal clotting.

Without enough factor VIII, bleeding can occur spontaneously or after injury, and can lead to serious complications such as joint damage, chronic pain, and life-threatening bleeding.

Phase 3 Study Examines Bleeding Rate

Efanesoctocog alfa works by providing sustained factor VIII activity. Unlike other factor VIII replacement therapies, efanesoctocog alfa is designed to overcome the von Willebrand factor–imposed half-life ceiling, meaning it can provide higher and more sustained levels of factor VIII activity than other treatments.

To evaluate the safety and efficacy of efanesoctocog alfa, Annette von Drygalski, MD, PharmD, Division of Hematology and Oncology, Department of Medicine, University of California, San Diego, and a team of investigators, conducted a phase 3 study involving 159 patients 12 years and older with severe hemophilia A from 48 centers across 19 countries.

The investigation included 2 groups of patients: group A received once-weekly prophylaxis with efanesoctocog alfa (50 IU per kilogram of body weight) for 52 weeks, while group B received on-demand treatment with efanesoctocog alfa for 26 weeks, followed by once-weekly prophylaxis with efanesoctocog alfa for 26 weeks.

The primary endpoint was the mean annualized bleeding rate in group A, and the key secondary end point was an intrapatient comparison of the annualized bleeding rate during prophylaxis in group A with the rate during prestudy factor VIII prophylaxis.

Efanesoctocog Alfa Outperforms Prestudy Factor VIII Prophylaxis

Results showed that in group A, the median annualized bleeding rate was 0, and the estimated mean annualized bleeding rate was 0.71. The mean annualized bleeding rate decreased from 2.96 to 0.69, a finding that exhibited superiority over prestudy factor VIII prophylaxis.

Additionally, efanesoctocog alfa demonstrated an acceptable side-effect profile, and the development of inhibitors to factor VIII was not observed. 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, pain intensity, and joint health.

“Significant improvements in physical health, pain, and joint health were shown. Furthermore, 80% (group A) and 85% (group B) of patients had zero spontaneous bleeding episodes during the prophylaxis periods,” investigators wrote. “When bleeding events did occur, a single injection of 50 IU per kilogram of efanesoctocog alfa provided effective resolution for 97% of such events.”

References:

1. von Drygalski A, CHowdry P, Kulkarni R, et al. Efanesoctocog Alfa Prophylaxis for Patients with Severe Hemophilia A. N Engl J Med 2023; 388:310-318. DOI: 10.1056/NEJMoa2209226