NEJM publishes once-weekly efanesoctocog alfa phase III data demonstrating its potential to transform the treatment landscape for people with hemophilia A

These data demonstrate that efanesoctocog alfa delivered normal to near-normal factor activity levels ( greater than 40%) for the majority of the week with once-weekly dosing. Efanesoctocog alfa is currently under priority review by the FDA and the target action date for the decision is February 28, 2023.

Angela Weyand, MD ,Investigator of the XTEND-1 Clinical Trial and Associate Professor at Michigan Medicine stated “We are excited about the potential for efanesoctocog alfa to address unmet needs by allowing people living with hemophilia to enjoy an active lifestyle. Currently, they often need to make trade-offs between bleed protection and dosing frequency. 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 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.”

The data from the pivotal XTEND-1 Phase III study published in NEJM show that efanesoctocog alfa met primary and key secondary endpoints, demonstrating clinically meaningful prevention of bleeds and superior bleed protection compared to prior factor VIII prophylaxis based on an intra-patient comparison. Treatment with efanesoctocog alfa prophylaxis resulted in significant and clinically meaningful improvements in physical health, pain, and joint health.

Key results include: i. The median and mean annualized bleeding rates (ABR) were 0.00 (IQR: 0.00-1.04) and 0.71 (95% CI: 0.52-0.97), respectively. ii. A statistically significant and clinically meaningful reduction in ABR (77%) versus prior factor VIII prophylaxis (p<0.001). iii. nearly all (97%) bleeding episodes resolved with a single injection of efanesoctocog alfa (50 iu kg). efanesoctocog alfa provided mean factor activity greater than 40 iu dl for the majority of the week and at 15 iu dl at day 7. iv. efanesoctocog alfa prophylaxis improved physical health (p><0.001), pain intensity (p="0.03)," and joint health (p="0.01)" when comparing 52 week and baseline measurements. v. in patients with target joints at baseline, 100% of the target joints were resolved after at least 12 months of continuous prophylaxis. vi.efanesoctocog alfa was well-tolerated, and inhibitor development to factor viii was not detected. the most common treatment-emergent adverse events ( greater than 5% of participants overall) were headache, arthralgia, fall, and back pain.

Quality of life data from the XTEND-1 study were recently presented at the 64th American Society of Hematology (ASH) Annual Meeting & Exposition. The findings provided further evidence of the potential positive impact of once-weekly efanesoctocog alfa prophylaxis to provide normal to near-normal factor activity levels for the majority of the week, reduce pain, and improve physical functioning for people with hemophilia A.

See-"Efanesoctocog Alfa Prophylaxis for Patients with Severe Hemophilia A"; Annette von Drygalski, M.D., Pharm.D., R.M.S.K., Pratima Chowdary, M.D., Roshni Kulkarni, M.D., et al., for the XTEND-1 Trial Group.January 26, 2023 .N Engl J Med 2023; 388:310-318 DOI: 10.1056/NEJMoa2209226.