PB0656 - Comparability of bleeding outcomes by prophylactic FVIII replacement intensity: A post-hoc analysis of a non-interventional study of men with severe hemophilia A

Background: Study BMN 270-902 collected real-world data on outcomes of a global cohort of people with severe hemophilia A (SHA) receiving regular exogenous factor VIII (FVIII) prophylaxis. Intensity of prophylactic treatment varied widely and may have impacted the findings.

Aims: To verify consistency in bleeding outcomes between those receiving high- and low-intensity prophylactic FVIII replacement in study BMN 270-902.

Methods: Post-hoc analysis of adult males with SHA (FVIII ≤1 IU/dL) receiving prophylactic FVIII replacement enrolled in BMN 270-902, a non-interventional Phase 3 lead-in study (providing 6 months of retrospective data at baseline and up to 12 months prospective data). Adeno-associated virus serotype 5 total antibody negative participants with ≥6 months follow-up were stratified by annualized FVIII utilization for prophylaxis per the third edition of the World Federation Hemophilia treatment guidelines (low-dose, < 4000 IU/kg/year; high-dose, ≥4000 IU/kg/year) at baseline. Mean annualized bleeding rate (ABR, treated and all bleeds) and proportion of participants with zero bleeds (treated and all bleeds) were compared.

Results: Among 194 participants, mean (SD) baseline annualized FVIII utilization was 5499.6 (1751.4) and 2838.0 (705.7) IU/kg/year and mean annualized FVIII infusion rate was 146.7 (42.0) and 120.2 (46.0) infusions per year for high-dose (n=78) and low-dose (n=116) intensity cohorts, respectively (Table 1). Median (range) follow-up time for bleeding outcomes was 223 (171–469) days. Throughout follow-up, mean annualized FVIII utilization was 5236.5 (1665.9) and 3065.5 (1188.4) IU/kg/year and mean calculated ABR for treated bleeds was 5.09 (7.08) and 4.38 (6.52) in the high- and low-dose cohorts, respectively; absolute difference in mean ABR for treated bleeds was 0.71 (P=0.4761). Absolute difference in proportion of participants with zero treated bleeds was 0.7% (34.6% vs 35.3%; P=0.7708). Similar trends were observed for all bleeds (Table 2).

Conclusion(s): Intensity of prophylaxis did not impact bleeding outcomes in study BMN 270-902. Funded by BioMarin.