OBJECTIVES : Primary prophylaxis, using factor VIII replacement, is the recognised standard of care for patients with severe haemophilia A. Recombinant factor VIII-Fc fusion protein (rFVIIIFc) and emicizumab, a recombinant humanised, bispecific, monoclonal antibody, are approved for the routine prophylaxis of bleeding episodes in patients of all ages with severe haemophilia A. These products have different mechanisms of action, methods of administration and treatment schedules. Although direct comparison of these therapeutic strategies would be beneficial, such a comparison is difficult without evidence from head-to-head clinical trials. The aim of this study was to compare the efficacy of rFVIIIFc and emicizumab for the treatment of haemophilia A, based on respective clinical trial evidence.

METHODS : The approved dosing regimens for each product, rFVIIIFc individualised prophylaxis and emicizumab administered once every week (Q1W), every two weeks (Q2W) or every four weeks (Q4W), were compared. Since clinical evidence did not form a connected network, the comparison was conducted using a matching‑adjusted indirect comparison. Individual patient data for rFVIIIFc (A‑LONG trial) was matched to aggregated characteristics of patients from the emicizumab HAVEN clinical trial programme and compared regarding mean annualised bleeding rate (ABR) and proportion of patients with zero bleeds.

RESULTS : After matching, no significant differences were observed between mean ABR for rFVIIIFc individualised prophylaxis and emicizumab administered Q1W, Q2W or Q4W. The population‑adjusted proportion of patients with zero bleeds was statistically significantly higher with rFVIIIFc compared with emicizumab Q4W (51.2% vs 29.3%, respectively; OR 2.53 [95%CI 1.09, 5.89]) and at least as comparable with emicizumab Q1W (47.6% vs 46.5%; OR 1.05 [95%CI 0.60, 1.82]), and emicizumab Q2W (54.2% vs 40.0%; OR 1.78 [95%CI 0.62, 5.11]).

CONCLUSIONS : Results of this population-adjusted indirect treatment comparison indicate that rFVIIIFc is more efficacious than emicizumab Q4W and at least as effective as more frequent emicizumab regimens for the management of haemophilia A.