1. Efanesoctocog alfa was superior to prestudy factor VIII prophylaxis in preventing bleeding in patients with severe hemophilia A. 

2. The treatment also resulted in improvement in physical health, pain level, and joint health.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Hemophilia A is a hereditary bleeding disorder due to a deficiency in coagulation factor VIII. Regular prophylaxis with factor VIII replacement, either with plasma-derived concentrates or recombinants, is necessary in preventing life-threatening bleeds and reducing the incidence of bleeding into joints, which contributes significantly to chronic pain and arthropathy in hemophilia A patients. Current factor VIII replacement products have limited half-lives from the effect of endogenous von Willebrand factor (VWF), requiring frequent administration. Efanesoctocog alfa is a recombinant factor VIII formulated with additional components to inhibit this effect and enable longer treatment intervals. The current study was a phase three trial to investigate the efficacy of efanesoctocog alfa in patients with severe hemophilia A previously receiving another prophylaxis. It was found that at 52 weeks, once-weekly efanesoctocog alfa resulted in near-physiological factor VIII activity, superior bleeding prevention, physical health improvements, pain relief, and joint health compared to the pre-study prophylaxis. These results showed that efanesoctocog alfa given once weekly provided superior efficacy in treating severe hemophilia A compared to other existing prophylaxis.

Click here to read the study in NEJM

Relevant Reading: BIVV001 Fusion Protein as Factor VIII Replacement Therapy for Hemophilia A

In-Depth [randomized controlled trial]: The current study was a phase three open-label, multi-center study to investigate the efficacy of efanesoctocog alfa in the treatment of severe hemophilia A. Patients 12 years of age or older with endogenous factor VIII activity of less than 1 international unit (IU)/dL or a known genotype for severe hemophilia A were eligible. Included patients must have had at least 150 days of exposure to factor VIII replacement therapy. Exclusion criteria included coagulation disorders and hypersensitivity to factor VIII therapies. Patients were assigned to groups A and B based on their previous factor VIII regimens: group A patients (n=133) had been receiving regular prophylactic treatments and received efanesoctocog alfa at 50 IU/kg once weekly for 52 weeks, and group B patients (n=26) had been receiving on-demand treatments received on-demand efanesoctocog alfa at 50 IU/kg for 26 weeks, followed by once-weekly treatment for another 26 weeks. Overall, among group A patients, the median annualized bleeding rate was 0 (interquartile range 0 to 1.04), and the mean annualized bleeding rate was 0.71 (95% Confidence Interval [CI] 0.52 to 0.97). Compared to the pre-study prophylaxis, the mean annualized bleeding rate declined from 2.96 (95% CI 2.00 to 4.37) to 0.69 (95% CI 0.43 to 1.11), confirming superiority (p<0.001). Of bleeding episodes, 97% resolved with one injection of efanesoctocog alfa. It was found that patients in group A reported improved physical health (p<0.001), pain severity (p=0.03), and joint health (p=0.01). In summary, efanesoctocog alfa was shown to be a stable recombinant factor VIII product and its once-weekly administration was superior to pre-study prophylaxis therapies in the treatment of severe hemophilia A.

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