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.

 

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Conflict of Interest:

JO reports employee for University Clinic Bonn; advisor, research funding, speakers bureau, reimbursement of travel expenses, and consultant for Bayer, Biotest, CSL Behring, OctaPharma, Pfizer, Sobi, and Takeda; advisor, speakers bureau, reimbursement of travel expenses, and consultant for BioMarin, Chugai, Grifols, LFB, Roche, Novo Nordisk; reimbursement of travel expenses and consultant for Freeline; speakers bureau for Sanofi; speakers bureau, reimbursement of travel expenses, and consultant for Spark Therapeutics. BK reports advisor for Be Biotherapy and BioMarin; consultant for Novo Nordisk, Pfizer, and Sanofi. TL reports principal investigator of clinical trial for Sanofi and Sobi. PC reports advisor for Bayer, Boehringer Ingelheim, Apcintex, CSL Behring, Chugai, Freeline, Novo Nordisk, Pfizer, Roche, Sanofi, Spark, Sobi, and Takeda. LK reports advisor for Biomarin, Sanofi Genzyme, Roche, and CSL. OK reports advisor for Bayer, CSL Behring, Novo Nordisk, Pfizer, Roche, and Sobi. KF reports consultant for Chugai Pharmaceutical Co., Ltd and CellGenTech, Inc.; advisor for Chugai Pharmaceutical Co. Ltd, Bayer Yakuhin, Ltd., CSL Behring K.K., Japan Blood Products Organization, KM Biologics, Novo Nordisk, Pfizer Japan Inc, Fujimoto Pharmaceutical Corporation, Takeda Pharmaceutical Company Limited, Sanofi K.K., and Sekisui Medical Co., Ltd. AvD reports advisor for Biomarin, Regeneron, Pfizer, Bioverativ/Sanofi, CSL Behring, Novo Nordisk, Precision Medicine, Genentech, and UniQure; ownership of partnership for Hematherix Inc. ES, HP, and LB are employees of Sobi and may hold shares and/or stock options in the company. JD, AF, and SG are employees of Sanofi and may hold shares and/or stock options in the company.

Publication History

Article published online:
13 February 2025