Emicizumab long-term outcomes and coagulation biomarkers in mild or moderate hemophilia A without inhibitors (HAVEN 6)

Background Emicizumab, a bispecific monoclonal antibody, substitutes for activated factor (F)VIII, facilitating hemostasis in people with hemophilia A (HA). HAVEN 6 is a multicenter, open-label, single-arm phase 3 study of emicizumab in people with mild or moderate HA. At primary data cut-off, emicizumab demonstrated clinically meaningful bleed control and a favorable safety profile. Objectives To evaluate the long-term efficacy and safety of emicizumab in HAVEN 6. Methods Participants had mild (FVIII >5–<40 IU/dL) or moderate (FVIII ≥1–≤5 IU/dL) HA without FVIII inhibitors, warranting prophylaxis as assessed by the treating physician. Safety endpoints included adverse events (AEs) and AEs of special interest (e.g. thromboembolic events [TEs] and thrombotic microangiopathies). Efficacy endpoints included annualized bleed rates (ABR) for treated bleeds. Pharmacokinetics (PK), pharmacodynamics (PD), safety biomarkers of coagulation, and F8 genotypes were assessed. Further study details are published in the primary analysis (Négrier et al. Lancet Haematol 2023). Results At cut-off (December 11, 2023), median (interquartile range) follow-up was 155.9 (24.1–192.6) weeks (N = 72). In total, 481 AEs were reported; 93.1% of participants experienced ≥1 AE. Two TEs occurred, one since the primary analysis. Both participants continued emicizumab. Model-based ABR for treated bleeds was 1.0 (95% confidence interval: 0.71–1.35). Therapeutic emicizumab exposure levels were maintained throughout the study. FXIa-triggered thrombin generation peak height was higher compared with levels previously observed in people with severe HA. Safety biomarkers of coagulation were unaffected by emicizumab. F8 genotyping of participants found variants consistent with mild or moderate HA. Conclusions These long-term efficacy and safety data confirm emicizumab as a valuable treatment option for people with non-severe HA.