FDA Approves Efanesoctocog Alfa for Hemophilia A

The FDA approved efanesoctocog alfa, a recombinant factor VIII therapy with once-a-week dosing for hemophilia A.

Efanesoctocog alfa is the first factor VIII therapy to overcome the interaction with endogenous von Willebrand factor, which creates a ceiling of 8 to 19 hours on the half-life of current factor VIII replacement products, which in turn creates the need for more frequent dosing.

The approval comes just before the target action date for the FDA decision of February 28, 2023.

Data to support the approval came from the pivotal phase 3 XTEND-1 study (NCT04161495), which was an open label, global, nonrandomized interventional study assessing the safety, efficacy, and pharmacokinetics of once-weekly efanesoctocog alfa in patients 12 years or older (n = 159) with severe hemophilia A who were previously treated with factor VIII replacement therapy.

The study consisted of 2 parallel treatment arms: the prophylaxis arm A, where patients were treated with efanesoctocog alfa prophylaxis once a week intravenously for 52 weeks (n = 133); and the on-demand arm B, where those had received prior on-demand factor VIII therapy began 26 weeks of on-demand efanesoctocog alfa, switching to once-weekly prophylaxis for an additional 26 weeks (n = 26).

The primary end point was the mean annualized bleeding rate (ABR) 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. Additional end points included treatment of bleeding episodes, safety, pharmacokinetics, and changes in physical health, pain, and joint health.

In arm A, the median (IQR) ABR was 0 (0-1.04), and the estimated mean ABR was 0.71 (95% CI, 0.52-0.97). The mean ABR fell from 2.96 (95% CI, 2.00-4.37) to 0.69 (95% CI, 0.43-1.11), a finding that showed superiority over prestudy factor VIII prophylaxis (P < .001).

In the overall population, nearly all bleeding episodes (97%) resolved with 1 injection of efanesoctocog alfa.

Weekly prophylaxis with efanesoctocog alfa provided mean factor VIII activity of more than 40 IU/dL for most of the week and of 15 IU/dL at day 7.

Prophylaxis with efanesoctocog alfa for 52 weeks (group A) improved physical health, pain intensity, and joint health.

Efanesoctocog alfa was generally well tolerated, and inhibitor development against factor VIII was not detected. The most common treatment-emergent adverse events were arthralgia, back pain, falls, and headaches.