Once-weekly administration of efanesoctocog alfa (EA) as bleeding prophylaxis for patients with severe hemophilia A resulted in superior clinical outcomes compared with on-demand therapy and prior treatment with recombinant or plasma-derived factor VIII, according to the results of the phase 3 XTEND-1 study published in the New England Journal of Medicine.1
“We are excited about the potential for efanesoctocog alfa to address unmet needs by allowing people living with hemophilia to enjoy an active lifestyle,” lead investigator Angela Weyand, MD, of Michigan Medicine, said in a press release.2 “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.”
The multicenter, open-label, phase 3 XTEND-1 trial randomly assigned 159 patients aged 12 or older with previously-treated, severe hemophilia A to receive once-weekly EA prophylaxis for 52 weeks (group A) or on-demand EA for 26 weeks followed by once-weekly EA prophylaxis for an additional 26 weeks (group B).1 The primary endpoint was mean annualized bleeding rate (ABR) in group A. Secondary endpoints included intrapatient ABR comparison between prestudy prophylaxis and on-study prophylaxis, bleeding episodes, and changes in overall and joint health, and pain.
At baseline, the mean age was 35.4, and the majority of patients were White at 61%, with 18% who were Asian, 2% who were Black, and the remaining classified as other or not reported. The median age at first start of prophylaxis was 1.0 year and the number of bleeding episodes within the past year was 8.3 ±15.5.
The mean ABR was 0.71 among the 133 patients in group A. EA prophylaxis was superior to prestudy prophylaxis with recombinant or plasma-derived factor VIII, with a mean ABR of 0.69 compared with 2.96 (rate ratio [RR], 0.23; 95% CI, 0.13-0.42; P <.001).
There were 65% of patients in group A who experienced no bleeding episodes. The mean ABR for spontaneous bleeding and bleeding into joints was 0.29 and 0.52, respectively.
In group B, the mean ABR for spontaneous bleeding and bleeding into joints were 15.97 and 17.45, respectively, during the on-demand treatment period. During the prophylaxis period, the mean ABR decreased to 0.45 for spontaneous bleeds and 0.61 for joint bleeds.
Scores of physical health (P <.001), joint health (P =.01), and pain intensity (P =.03) were significantly improved with 52 weeks of EA prophylaxis.
None of the patients developed factor VIII inhibitors. The most common adverse events were headache, arthralgia, fall, and back pain. Serious adverse events developed among 9% of patients. There were no cases of serious allergic reaction, anaphylaxis, or vascular thrombotic events.
Dr Weyand concluded that “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.”2
Disclosures: This study was supported by Sanofi and Sobi. Please see the original reference for a full list of disclosures.
- von Drygalski A, Chowdary 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
- NEJM publishes once-weekly efanesoctocog alfa Phase 3 data demonstrating its potential to transform the treatment landscape for people with hemophilia A. News release. Paris and Stockholm; Sanofi; January 25, 2023.