Efanesoctocog alfa treatment outcomes in subjects≥50 years of age from the XTEND-1 trial

Introduction: The aging hemophilia population faces challenges compounded by limited data on factor therapy effectiveness. We performed post hoc assessment of patients≥50 years old treated with efanesoctocog alfa, a first-in-class high-sustained factor VIII therapy, during XTEND-1 (NCT04161495).

Method: Patients received once-weekly efanesoctocog alfa (50 IU/kg) prophylaxis (52 weeks) in Arm A. In Arm B, patients received efanesoctocog alfa (50 IU/kg) on-demand followed by once-weekly prophylaxis (26 weeks each). Endpoints included annualized bleed rate (ABR), factor consumption, Haemophilia Quality of Life Questionnaire for Adults (physical health), PROMIS Pain Intensity 3a T-score, Hemophilia Joint Health Score (HJHS), and safety.

Results: Twenty-nine patients≥50 years old (range: 50–72 years) enrolled in XTEND-1 (Arm A: n=21; Arm B: n=8). For patients with pre-study data available (n=13; Arm A), pre-study mean ABR was 3.89. Patients≥50 years old had an overall mean ABR of 1.0 in Arm A and 1.7 in Arm B during once-weekly efanesoctocog alfa (50 IU/kg) prophylaxis ([Fig. 1]). Arm A model-based mean (95% confidence interval [CI]) ABR was 1.05 (0.40–2.72) compared with 0.71 (0.52–0.97) in the overall population (n=133). One injection of efanesoctocog alfa (50 IU/kg) was sufficient to resolve 95% (n=19) of bleeds in Arm A and all bleeds (n=89) during Arm B on-demand and prophylactic periods. Mean (standard deviation) annualized consumption per patient during prophylaxis was 2784 (137) and 2766 (91) IU/kg in Arms A and B. In Arm A, mean baseline HJHS scores were higher for those≥50 years (41.1 vs 18.1 in the overall population); mean HJHS score improved by 4.0 (95% CI:−8.25, 0.25) points by Week 52 ([Fig. 2]). During this time, physical health was maintained and pain intensity remained unchanged. No patient developed inhibitors. Twenty (95%) patients in Arm A and 5 (63%) in Arm B had≥1 treatment-emergent adverse event (TEAE). Five (24%) patients and 1 (13%) patient in Arms A and B had≥1 serious TEAE, respectively. No thrombotic events or deaths occurred.

Fig. 1  Overall annualized bleed rate among patients≥50 years old in Arm A and B of XTEND-1

Fig. 2  Change from baseline in PROMIS Pain Intensity 3a T-score (n=19),Haem-A-QoL Physical Health Subscale Score (n=19), and HJHS (n=15) in patients≥50 years of age always on efanesoctocog alfa prophylaxis in Arm A of XTEND-1

Conclusion: Prophylactic once-weekly efanesoctocog alfa (50 IU/kg) provided effective bleed protection in patients≥50 years. ABR was comparable with the overall XTEND-1 population, and patients experienced joint health improvement.

This study was funded by Sanofi and Sobi.

Publication History

Article published online:
13 February 2025