Clinical Outcomes over 2 Years of Once-Weekly Efanesoctocog Alfa Treatment in Children with Severe Hemophilia A: Second Interim Analysis from the Phase 3 XTEND-ed Long-Term Extension Study
Authors: Malec Lynn , Nolan Beatrice , Chan Anthony K C , Albisetti Manuela , Chou Sheng-Chieh , Zulfikar Bulent , Simpson Mindy , Feng Liqi , Palmborg Helena , Neill Graham , Abad-Franch Lydia , Gunawardena Sriya , Fijnvandraat Karin 
Published: December 2024

Introduction

Efanesoctocog alfa (formerly BIVV001) is a first-in-class high-sustained factor VIII (FVIII) replacement therapy designed to overcome the von Willebrand factor-imposed half-life ceiling. Once-weekly efanesoctocog alfa 50 IU/kg was well tolerated and provided highly effective bleed protection in children with severe hemophilia A in the XTEND-Kids study (NCT04759131). Efanesoctocog alfa maintained high sustained FVIII activity throughout the weekly dosing interval in the normal to near-normal range of &gt;40 IU/dL for ~3 days and &gt;10 IU/dL for ~7 days at steady state. Here, we present data from the second interim analysis on the long-term safety and efficacy of efanesoctocog alfa in previously treated children with severe hemophilia A in the XTEND-ed study (NCT04644575).

Methods

XTEND-ed is a multicenter, open-label study that enrolled participants from previous Phase 3 studies, including children &lt;12 years of age who completed the XTEND-Kids study. Participants continued weekly 50 IU/kg prophylaxis with efanesoctocog alfa in XTEND-ed (Arm A). The primary endpoint is the occurrence of FVIII inhibitors (determined by the Nijmegen modified Bethesda assay). Secondary endpoints include annualized bleed rates (ABRs) for treated bleeds, efficacy for bleed treatment, and safety. Participants provided informed consent and XTEND-ed was approved by applicable ethics committees. Data cut: February 22, 2024.

Results

Of 74 males, 71 (age: &lt;6 years, n=35; 6-&lt;12 years, n=36) rolled over from XTEND-Kids to XTEND-ed. The median (range) treatment duration in XTEND-ed was 66.6 (36.3-100.6) weeks. The median (range) cumulative treatment duration from XTEND-Kids baseline was 119.1 (88.1-152.6) weeks. No FVIII inhibitors were detected. During XTEND-ed, the mean (standard deviation [SD]) ABR evaluated for Day 1-Month 6 (n=71) was 0.59 (1.38), Months 6-12 (n=71) was 0.77 (1.64), and Months 12-18 (n=53) was 0.71 (2.49), with 57 of 71 (80.3%), 54 of 71 (76.1%), and 44 of 53 (83.0%) participants with zero bleeds, respectively. The mean (95% confidence interval) model-based ABR for the whole efficacy period was 0.67 (0.48; 0.93). The mean (SD) spontaneous bleeds per participant was 0.1 (0.3) and traumatic bleeds per participant was 0.6 (0.9). Of 61 bleeds, 54 (88.5%) resolved with a single dose of efanesoctocog alfa 50 IU/kg, with the hemostatic response rated as excellent or good for 43/45 (95.6%) bleeds. The median (range) total weekly efanesoctocog alfa consumption due to prophylaxis and bleed treatment was 54.0 (47.1-74.1) IU/kg.

Overall, 55 (77.5%) participants experienced ≥1 treatment-emergent adverse event (TEAE) with 4 (5.6%) experiencing ≥1 serious TEAE. The commonly reported TEAEs were cough (14.1%), arthralgia (12.7%), and pyrexia (11.3%). Two treatment-related TEAEs were reported in one participant; left arm pain after injection and headache after injection. Serious TEAEs were partial seizures, muscle hematoma, head injury, and thermal burn reported for 1 (1.4%) participant, each; none were considered treatment related. None of the TEAEs led to death or treatment discontinuation. There were no thrombotic events.

Conclusion

The results from over 2 years in previously treated children with severe hemophilia A show that once-weekly efanesoctocog alfa continues to be well tolerated and provides highly effective bleed protection with no FVIII inhibitors reported.