PB1261 - Matching Adjusted Indirect Comparisons Between Personalized Prophylaxis with Simoctocog Alfa versus Standard Prophylaxis with Turoctocog Alfa in Adults with Severe Hemophilia A

Background: Prophylaxis with factor VIII (FVIII) concentrates to prevent bleeding episodes remains the mainstay of therapy for patients with severe hemophilia A. The lack of head-to-head studies precludes direct comparison of efficacy between different FVIII concentrate-specific regimens.

Aims: To indirectly compare the efficacy of a pharmacokinetics (PK)-guided personalized prophylaxis regimen with simoctocog alfa (Nuwiq®) against standard prophylaxis with turoctocog alfa (Novoeight®) in adults with severe hemophilia A using a matching adjusted indirect comparison (MAIC) methodology.

Methods: After matching study populations accounting for clinically important baseline characteristics, individual patient data (IPD) from 65 patients treated with simoctocog alfa from the NuPreviq study were compared against aggregate data for 126 patients on turoctocog alfa from the GUARDIAN-1 study. Three patients in NuPreviq who would have not met the inclusion criteria for GUARDIAN-1 were excluded from the analysis. Baseline age and body weight were used to re-weight the simoctocog alfa IPD such that the weighted summary statistics for these parameters matched the aggregate data reported for turoctocog alfa. Unanchored indirect treatment comparisons were performed for various clinical outcomes.

Results: After matching the two populations, the effective sample size (ESS) for simoctocog alfa was 43.1. The percentage of patients with zero bleeds was significantly higher with simoctocog alfa than turoctocog alfa (74.2% versus 28.6%) (Figure 1, Table 1). The total, spontaneous and joint annualized bleeding rates (ABRs) were significantly lower with simoctocog alfa (1.7, 1.0 and 0.9, respectively) than with turoctocog alfa (6.7, 4.6 and 5.2, respectively) (Table 1). The mean weekly dose was significantly higher in patients treated with simoctocog alfa (99.1 IU/kg versus 72.7 IU/kg) (Table 1).

Conclusion(s): A PK-guided personalized prophylaxis with simoctocog alfa can lead to significantly increased zero bleed rates and significantly decreased ABRs compared with standard prophylaxis with turoctocog alfa, albeit at a higher weekly dose.