Efanesoctocog Alfa versus Standard and Extended Half-Life Factor VIII Prophylaxis in Adolescent and Adult Patients with Haemophilia A without Inhibitors.

Abstract

In the Phase 3 XTEND-1 trial, (NCT04161495) efanesoctocog alfa prophylaxis provided superior bleed protection versus pre-study factor VIII (FVIII) replacement therapy in patients with severe haemophilia A. The aim of this study was to indirectly compare bleed outcomes between efanesoctocog alfa and standard/extended half-life (SHL and EHL) FVIII replacement therapies in adolescent and adult patients with severe haemophilia A without inhibitors. A systematic literature review was conducted to identify Phase 3 trials of EHL and SHL FVIII replacement therapies for comparison with efanesoctocog alfa data from XTEND-1. Matching-adjusted indirect comparisons were used to compare annualised bleeding rates (ABRs) for any, treated, joint, and spontaneous bleeds between efanesoctocog alfa and comparators. The estimates from respective comparisons were pooled using random-effect meta-analyses to evaluate the overall difference between efanesoctocog alfa and comparator therapies. Four EHL therapies (rurioctocog alfa pegol, efmoroctocog alfa, turoctocog alfa pegol, damoctocog alfa pegol) and two octocog alfa SHL therapies were included. In meta-analyses, efanesoctocog alfa was associated with significantly lower ABRs for any [mean difference (95% CI) -2.24 (-3.24; -1.25)], spontaneous [-1.52 (-2.33; -0.72)], and joint bleeds [-1.60 (-2.32; -0.88)] versus EHL therapies, and with significantly lower ABRs for any [-3.61 (-4.43; -2.79)], treated [-1.55 (-1.89; -1.20)], spontaneous [-2.52 (-3.31; -1.72)], and joint bleeds [-3.42 (-4.77; -2.08)] versus SHL therapies. Efanesoctocog alfa was associated with significantly lower ABRs (any, spontaneous and joint) compared with EHL or SHL prophylaxis therapies. Patients had, on average, 2.2 and 3.6 fewer bleeds per year versus EHL and SHL therapies, respectively.