Prospective collection of bleeding rate and factor usage in participants with hemophilia A and B in a noninvestigational product study.

BACKGROUND: We report efficacy and select safety outcomes of current factor prophylaxis of adults with moderately severe to severe hemophilia A (HA) or hemophilia B (HB) in a large, prospective, noninvestigational product study. OBJECTIVES: This study established prospective efficacy data on factor (F)VIII/FIX prophylaxis in the usual care setting. METHODS: This prospective, open-label, noninvestigational product, multicenter study (BENEGENE-1) included HA and HB cohorts. Participants remained on their current factor replacement therapy. The primary end point was annualized bleeding rate. Secondary end points included annualized infusion rate of FVIII/FIX replacement therapy. Safety data were also collected. RESULTS: In total, 241 individuals with HA and 333 with HB were screened, and 101 and 111, respectively, were enrolled in this study. The most common reason for screen failure was adeno-associated virus neutralizing antibody positivity, accounting for 82.1% and 92.3% of screen failures in the HA and HB cohorts, respectively. The corresponding overall mean (SD; range) follow-up duration was 310.8 (209.2; 14-948) and 498.6 (293.4; 117-1269) days. Mean (SD) total annualized bleeding rate and annualized infusion rate were 6.1 (10.6) and 127.1 (51.8) for participants with HA and 4.5 (9.4) and 62.8 (33.3) for participants with HB, respectively. No new safety concerns were identified with FVIII/FIX replacement therapy. CONCLUSION: This study provides a robust, prospective, informative dataset on bleeding rates in participants receiving factor replacement therapy over a mean follow-up of ∼1 year. Although FVIII/FIX prophylaxis was generally well tolerated, bleeding rate data illustrate the limitations of current standard-of-care factor prophylaxis.