Real-world experience of efanesoctocog alfa in Hemophilia A patients in the US: A retrospective analysis Free

Introduction Efanesoctocog alfa is a first-in-class, high-sustained factor VIII (FVIII) replacement therapy designed to overcome the half-life limitations imposed by von Willebrand factor (VWF). In pivotal Phase 3 trials, XTEND-1 (NCT04161495) and XTEND-Kids (NCT04759131), once-weekly efanesoctocog alfa (50 IU/kg) was well tolerated and provided highly effective bleed protection in adults and children with severe hemophilia A. Real-world data on efanesoctocog alfa in routine U.S. clinical practice remain limited. The aim of this retrospective chart review was to investigate treatment patterns and outcomes associated with efanesoctocog alfa used for prophylaxis, on-demand, or perioperative management of bleeds in adults and children with hemophilia A who switched from previous standard-of-care therapies in the United States.

Methods This was a multicenter, retrospective, observational chart review conducted across four clinical sites in the United States. The study included adult and pediatric patients with a diagnosis of hemophilia A who switched from a prior therapy (standard half-life FVIII [SHL]; extended half-life FVIII [EHL] or non-factor therapy [emicizumab]) to efanesoctocog alfa in routine clinical practice. Data was extracted from medical records, and patients were stratified into three cohorts based on treatment approach: prophylaxis, on-demand, and perioperative management. Patient identification period was February 23, 2023, to December 1, 2024, for the prophylaxis and on-demand cohorts, and to October 31, 2024, for the perioperative cohort.

Results The retrospective chart review included 41 hemophilia A patients, with a median (interquartile range [IQR]) age of 21 (13–32) years and most patients were male (39 [95.1%]). Of these patients, 31 (75.6%) had severe hemophilia A, and 5 (12.2%) each had moderate or mild forms. Patients were stratified into prophylaxis (n=34), on-demand (n=5), and perioperative (n=3) cohorts; one patient enrolled in the prophylaxis cohort was also concurrently included in the perioperative cohort. The overall median (IQR) duration of efanesoctocog alfa treatment was 14.0 (10.7–15.1) months, with a median (IQR) dose per injection of 50 (49.0–50.0) IU/kg. Most patients (35 [89.7%]) received efanesoctocog alfa as a once-weekly injection. Among the prophylaxis and on-demand cohorts, 12 patients previously on SHL and 12 on EHL FVIII products switched to efanesoctocog alfa, primarily due to its longer half-life, which resulted in reduced injection frequency and better protection from joint bleeds. In the prophylaxis cohort, mean (SD) annualized bleeding rates (ABRs) decreased from 1.5 (1.57) to 1.2 (1.95) in the SHL group and from 2.2 (2.44) to 0.6 (1.07) in the EHL group following the switch to efanesoctocog alfa. Additionally, 13 patients who switched from emicizumab to efanesoctocog alfa reported improved bleed protection during physical activity and better control of joint bleeds as the main reasons for the switch. After switching from emicizumab to efanesoctocog alfa prophylaxis, mean (SD) ABRs declined from 1.6 (1.5) to 0.7 (0.7). In the perioperative cohort, four surgical procedures were documented in three patients: osteotomy of the right thumb, tooth extraction, knee replacement, and vasectomy. No unexpected bleeding events occurred, and no patients required blood transfusions. The primary reason for selecting efanesoctocog alfa in the perioperative setting was improved bleed protection with fewer injections. Due to the retrospective nature of this chart review, adverse event data were not collected.

Conclusion This retrospective chart review provides real-world evidence that efanesoctocog alfa is a safe and highly effective treatment for hemophilia A across all severities in the pediatric and adult population. Patients experienced improved bleed protection, especially joint bleeds, and required fewer injections compared to SHL/EHL. Comparisons before and after the switch to efanesoctocog alfa showed a meaningful reduction in ABRs, highlighting that clinical outcomes in real world use were consistent with those observed in the clinical trial program.