Matching‐adjusted indirect comparison of bleeding outcomes in severe haemophilia A: Comparing valoctocogene roxaparvovec gene therapy, emicizumab prophylaxis, and FVIII replacement prophylaxis

Abstract

AbstractIntroductionHead‐to‐head evaluation of valoctocogene roxaparvovec, the first gene therapy approved for haemophilia A, with emicizumab is not available. Therefore, phase 3 trial data were indirectly compared.AimTo compare bleeding rates in trials evaluating 6 × 1013 vg/kg valoctocogene roxaparvovec (GENEr8‐1; NCT03370913), 1.5 mg/kg emicizumab dosed every week (HAVEN 3; NCT02847637), and FVIII prophylaxis (270–902) in participants with severe haemophilia A (FVIII ≤1 IU/dL).MethodsValoctocogene roxaparvovec versus emicizumab and FVIII prophylaxis as used in 270–902 versus emicizumab cross‐trial comparisons were performed using matching‐adjusted indirect comparison (MAIC). Individual participant data from GENEr8‐1 and 270–902 were weighted to equalise aggregate participant baseline characteristics from HAVEN 3. After MAIC weighting, annualised bleeding rates (ABR) and proportions of participants without bleeds were compared for treated bleeds, all bleeds, treated joint bleeds, and treated spontaneous bleeds.ResultsAfter MAIC weighting, ABR for all bleeds was statistically significantly lower with valoctocogene roxaparvovec than emicizumab (rate ratio [95% CI], .55 [.33–.93]). Additionally, significantly higher proportions of participants had no treated joint bleeds (odds ratio [95% CI], 2.75 [1.20–6.31]) and no treated bleeds (3.25 [1.53–6.90]) with valoctocogene roxaparvovec versus emicizumab. When compared with the mainly standard half‐life FVIII prophylaxis regimens in 270–902, mean ABRs (except for all bleeds) were significantly lower, and significantly higher proportions reported 0 bleeds for all outcomes with emicizumab.ConclusionValoctocogene roxaparvovec provided generally lower bleeding rates and higher probability of no bleeds, including treated joint bleeds, than emicizumab. Emicizumab was more effective than FVIII prophylaxis regimens used in 270–902.