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

• DOI: 10.1111/hae.14818
• Publication Date: 2023-06-24T21:35:06Z
• Authors: Jan Astermark; Tyler W Buckner; Laurent Frenzel; Anthony J Hatswell; Xiaojun You; Hai Liu; Erin Goodman; Sandra Santos; Charles Hawes; David Hinds; Robert Klamroth
• Keywords: emicizumab; Factor VIII; haemophilia A; Hemorrhage; Genetic Therapy; 16. Peace & justice; Hemophilia A; AAV5-hFVIII-SQ; FVIII prophylaxis; matching-adjusted indirect comparison (MAIC); Antibodies, Bispecific; Hemarthrosis; Humans; valoctocogene roxaparvovec

Abstract Introduction Head‐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. Aim To compare bleeding rates in trials evaluating 6 × 10 13 vg/kg roxaparvovec (GENEr8‐1; NCT03370913), 1.5 mg/kg dosed every week (HAVEN 3; NCT02847637), and FVIII prophylaxis (270–902) participants severe A (FVIII ≤1 IU/dL). Methods Valoctocogene versus as used 270–902 cross‐trial comparisons performed using matching‐adjusted indirect comparison (MAIC). Individual participant from GENEr8‐1 weighted to equalise aggregate baseline characteristics HAVEN 3. After MAIC weighting, annualised (ABR) proportions without bleeds compared treated bleeds, all joint spontaneous bleeds. Results ABR was statistically significantly lower than (rate ratio [95% CI], .55 [.33–.93]). Additionally, higher had no (odds 2.75 [1.20–6.31]) (3.25 [1.53–6.90]) emicizumab. When mainly standard half‐life regimens 270–902, mean ABRs (except bleeds) lower, reported 0 outcomes Conclusion provided generally probability including Emicizumab more effective 270–902.