Emicizumab long-term outcomes and coagulation biomarkers in mild or moderate hemophilia A without inhibitors (HAVEN 6)
Cedric Hermans, Víctor Jiménez-Yuste, Giuliana Ventriglia, Anna Kiialainen, Laurent Frenzel, Olivier Catalani, Jerzy Windyga, Johannes Oldenburg, Christophe Schmitt, Amy D. Shapiro, Johnny Mahlangu, Michaela Lehle, Steven W. PipeBackground
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
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.
Conclusions
These long-term efficacy and safety data confirm emicizumab as a valuable treatment option for people with non-severe HA.