Joint Health Outcomes with Efanesoctocog Alfa in Adults/Adolescents from XTEND-1 Continuing XTEND-ed

Introduction Efanesoctocog alfa is a first-in-class high sustained factor VIII replacement therapy that overcomes the von Willebrand factor-imposed half-life ceiling. XTEND-1 (NCT04161495) showed once-weekly efanesoctocog alfa was well tolerated in adults/adolescents with severe hemophilia A providing superior bleed prevention over prior factor VIII prophylaxis. Participants completing the 1-year XTEND-1 trial could continue weekly efanesoctocog alfa (50 IU/kg) in XTEND-ed (NCT04644575) Arm A.Here, we report data on long-term joint health with efanesoctocog alfa in adults/adolescents aged≥12 years from XTEND-1 baseline through XTEND-ed second interim analysis (datacut: February 22, 2024). Method Participants provided informed consent; the study was approved by applicable review boards. Change in Hemophilia Joint Health Scores (HJHS; range 0–124) from parent study (XTEND-1) baseline to XTEND-ed Month 24 are presented descriptively.Individual joints (left/right elbows, knees, ankles) were scored according to 8 HJHS domains; gait score ranged from 0 to 4. Improved/worsened and unchanged HJHS scores are defined by decreases/increases of≥4 points, no change (or constant) of between -3 and+3 points, respectively. Results In total, 132/146 participants had evaluable HJHS scores at XTEND-1 baseline; median (range) total HJHS score was 19 (0, 98); (mean [SD]: 20.5 [18.4]). Median (range) treatment duration from XTEND-1 baseline was 170.5 (46.3–192.6) weeks. HJHS total score ([ Fig. 1 ]) and HJHS domain scores ([ Fig. 2 ]) improved over 3 years of efanesoctocog alfa prophylaxis, from XTEND-1 baseline to XTEND-ed Month 24. Mean (SD) HJHS gait scores remained unchanged: baseline, 1.7 (1.6); Month 24, 1.6 (1.6). At Month 24, the greatest changes in domain scores were for flexion loss -0.4 (2.4) and swelling -0.4 (1.8). HJHS total score improved or remained constant in 88% of evaluable participants (n=115). Fig. 1 Change in HJHS total score from parent study (XTEND-1) baseline to XTEND-ed baseline, Month 12, and Month 24 in participants aged≥12 years Fig. 2 Mean HJHS subdomain scores for participants aged≥12 years at parent study (XTEND-1) baseline, and XTEND-ed baseline, Month 12, and Month 24 Conclusion Overall improvements in joint health observed following 1 year of weekly efanesoctocog alfa prophylaxis are maintained through>3 years in adults/adolescents with severe hemophilia A. Study funded by Sanofi and Sobi. Acknowledgments Medical writing support for the development of this abstract was provided by Patricio Atanes, PhD, and Helen Jones, PhD, of Envision Pharma Group, and was funded by Sanofi and Sobi. The authors thank Alicia Mack, PharmD (Sanofi) and Nick Fulcher, PhD, CMPP (Sobi) for publication coordination, and Alejandro Fernández (Sanofi) for early guidance on the conceptualization of the study abstract. Sanofi and Sobi personnel reviewed this abstract. The authors had full editorial control of the abstract and provided their final approval of all content. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany