Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis of a phase 3b, open-label trial.

Subcutaneous emicizumab enables prophylaxis for people with hemophilia A (HA) from birth, potentially reducing risk of bleeding and intracranial hemorrhage (ICH). HAVEN 7 (NCT04431726) is the first clinical trial of emicizumab dedicated to infants, designed to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab in those ≤12 months of age with severe HA without factor (F)VIII inhibitors. Participants in this phase 3b trial received emicizumab 3 mg/kg maintenance dose every 2 weeks for 52 weeks, and are continuing emicizumab during the 7-year long-term follow-up. Efficacy endpoints included annualized bleed rate (ABR): treated, all, treated spontaneous, and treated joint bleeds. Safety endpoints included adverse events (AEs), thromboembolic events (TEs), thrombotic microangiopathies (TMAs), and immunogenicity (anti-emicizumab antibodies [ADAs] and FVIII inhibitors). At primary analysis, 55 male participants had received emicizumab (median [range] treatment duration: 100.3 [52-118] weeks). Median (range) age at informed consent was 4.0 months (9 days-11 months 30 days). Model-based ABR (95% confidence interval [CI]) for treated bleeds was 0.4 (0.30-0.63), with 54.5% of participants (n = 30) having zero treated bleeds. No ICH occurred. All 42 treated bleeds in 25 (45.5%) participants were traumatic. Nine (16.4%) participants had ≥1 emicizumab-related AE (all Grade 1 injection-site reactions). No AE led to treatment changes. No deaths, TEs, or TMAs occurred. No participant tested positive for ADAs. Two participants were confirmed positive for FVIII inhibitors. This primary analysis of HAVEN 7 indicates that emicizumab is efficacious and well tolerated in infants with severe HA without FVIII inhibitors.