Clinical Outcomes over 3 Years of Once-Weekly Efanesoctocog Alfa Treatment in Adults and Adolescents with Severe Hemophilia A: Second Interim Analysis from the Phase 3 XTEND-ed Long-Term Extension Study

Introduction

Efanesoctocog alfa (formerly BIVV001) is a first-in-class high-sustained factor VIII (FVIII) replacement therapy designed to decouple FVIII from endogenous von Willebrand factor. In the Phase 3 XTEND-1 study (NCT04161495), once-weekly efanesoctocog alfa demonstrated superior bleed protection over prior FVIII prophylaxis, was well tolerated, and provided FVIII activity within the normal to near-normal (>40%) range for most of the week. Here we present data from the second interim analysis of the long-term safety and efficacy of efanesoctocog alfa in adults and adolescents with severe hemophilia A in the XTEND-ed study (NCT04644575).

Methods

Previously treated patients (≥12 years) who completed XTEND-1 could continue efanesoctocog alfa (50 IU/kg, once-weekly) prophylaxis in the multicenter, open-label, long-term XTEND-ed study (Arm A). The primary endpoint is incidence of FVIII inhibitor development (determined by the Nijmegen modified Bethesda assay). Secondary endpoints include annualized bleed rates (ABRs), efficacy for bleed treatment, patient-reported quality of life (QoL) outcomes, and safety. XTEND-ed was approved by local ethics committees; participants provided informed consent. Data cut: February 22, 2024.

Results

A total of 146 participants (including 1 female) rolled over from XTEND-1 to Arm A of XTEND-ed (age: 12–17 years, n=21; 18–64 years, n=120; ≥65 years, n=5). The median (range) treatment duration in XTEND-ed was 120.6 (14.1–140.6) weeks comprising a median (range) of 121.5 (14–147) exposure days (EDs). The median (range) cumulative treatment duration from XTEND-1 baseline was 170.5 (46.3–192.6) weeks with median (range) 171.5 (47–201) EDs. FVIII inhibitors were not detected. During XTEND-ed, the mean (standard deviation [SD]) ABRs for Day 1–Month 6 (n=146) was 0.63 (1.6), Months 6–12 (n=144) was 0.77 (1.54), Months 12–18 (n=139) was 0.65 (1.67), and Months 18–24 (n=138) was 0.58 (1.64). The number of participants with zero bleeds for Day 1–Month 6 was 116 of 146 (79.5%), Months 6–12 was 107 of 144 (74.3%), Months 12–18 was 109 of 139 (78.4%), and Months 18–24 was 111 of 138 (80.4%). The mean (95% confidence interval) model-based ABR for the whole efficacy period was 0.64 (0.50; 0.82). Of 205 treated bleeding episodes, 194 (94.6%) resolved with 1 injection of efanesoctocog alfa; participants rated the response as excellent/good for 139/160 (86.9%) bleeds. The median (range) total weekly efanesoctocog alfa consumption was 51.6 (39.4–61.0) IU/kg. The Haem-A-QoL total score and physical health score, analyzed in 102 participants (age: ≥17 years), showed an improvement with mean (SD) change from baseline (XTEND-1) to XTEND-ed Month 24 of -5.8 (13.35) and -7.5 (20.05), respectively.

Overall, 117 (80.1%) participants experienced ≥1 treatment-emergent adverse event (TEAE), the most commonly reported being COVID-19 (25.3%), arthralgia (15.1%), and nasopharyngitis (12.3%). Twenty-two participants (15.1%) experienced ≥1 serious TEAE including 2 participants with thromboembolic events: one was a deep vein thrombosis following corrective surgery for a femur fracture (in the setting of treatment with another FVIII product), the other was a cerebral infarction in a participant with pre-existing atrial fibrillation and other risk factors; neither event was related to efanesoctocog alfa treatment.

Conclusion

Long-term results in adults and adolescents in XTEND-ed shows that once-weekly efanesoctocog alfa continues to provide high efficacy and is well tolerated. No inhibitors were detected and ABRs remained low, with continued improvement observed for overall QoL.