Once-Weekly Therapy Prevents Bleeding in Patients With Severe Hemophilia A

A once-weekly prophylactic treatment with an investigational recombinant factor VIII therapy led to normal or near-normal factor VIII activity levels in patients with severe hemophilia A, according to results from a phase 3 study published in the New England Journal of Medicine.

Efanesoctocog alfa (Sanofi, Sobi) is the first investigational factor VIII therapy that has been shown to break through the von Willebrand factor (VWF) ceiling, which imposes a half-life limitation on current factor VIII therapies.

In the XTEND-1 trial, patients 12 years of age or older with severe hemophilia A received either once-weekly prophylaxis with efanesoctocog alfa (50 IU per kilogram of body weight) for 52 weeks (group A) or on-demand treatment with efanesoctocog alfa for 26 weeks, followed by once-weekly prophylaxis with efanesoctocog alfa for 26 weeks (group B). The primary end point was the mean annualized bleeding rate in group A. 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.

Among 133 patients 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, which a finding that showed superiority over prestudy factor VIII prophylaxis; 80% of patients had no episodes of spontaneous bleeding. Among 26 patients in group B, 97% of bleeding episodes during the on-demand period resolved with one injection of efanesoctocog alfa. During the prophylactic period, 85% of patients reported no episodes of spontaneous bleeding.

Furthermore, 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. Weekly prophylaxis was also associated with improved physical health, pain intensity and joint health.

According to investigators, uncoupling recombinant factor VIII from VWF may reduce interpatient pharmacokinetic variability of efanesoctocog alfa and increase the predictability of the factor VIII profile over time. Furthermore, the low variability in efanesoctocog alfa clearance may allow the use of a standard weekly dose of 50 IU per kilogram for prophylaxis and reduce the need to monitor factor VIII activity levels for individualized pharmacokinetic-based prophylaxis.

“Based on the XTEND-1 study results assessing efanesoctocog alfa, we have the opportunity to provide near normal factor activity levels for an extended period of time (the majority of a week) with a single dose, which is a first for hemophilia A,” said Angela Weyand, MD, the study’s investigator. “The data show that efanesoctocog alfa can offer patients increased bleed protection, leading to improved outcomes, such as reduced pain and improved physical functioning, that may impact daily life with a reduced treatment burden.”