HAVEN 7 Trial Evaluates Emicizumab Prophylaxis in Infants With Hemophilia A

A group of researchers conducted a study evaluating the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of emicizumab in infants from birth to age ≤12 months who have hemophilia A without factor VIII (FVIII) inhibitors. The HAVEN 7 trial study included 55 male participants who were recruited between February 2021 and May 2022. For the study, participants received emicizumab subcutaneously at 3 mg/kg once weekly for 4 weeks as a loading dose, followed by of 3 mg/kg once every 2 weeks for a total of 52 weeks as maintenance dosing.

The efficacy of emicizumab was evaluated based on bleed end points, including treated bleed rate, all bleed rate, treated spontaneous bleed rate, and treated joint bleed rate. After 52 weeks of treatment, participants continued to receive emicizumab 3 mg/kg once every 2 weeks. They also had the option to switch to 1.5 mg/kg once a week or 6 mg/kg once every 4 weeks for the 7-year follow-up period. Participants with >2 qualifying bleeds—defined as spontaneous, clinically significant, clinician verified, and occurring while receiving emicizumab maintenance—within a 12-week interval could have their dose up-titrated to 3 mg/kg once a week from week 17.

The researchers assessed the safety of emicizumab by looking at the incidence and severity of adverse events (AEs), including AEs leading to emicizumab discontinuation, injection-site reactions, thromboembolic events (TEs) or thrombotic microangiopathies (TMAs), severe hypersensitivity, anaphylaxis, and anaphylactoid events.

All 55 participants completed 52 weeks in the study and received emicizumab prophylaxis 3 mg/kg once every 2 weeks. After entering the long-term follow-up period, 49 participants (89.1%) continued to receive emicizumab 3 mg/kg once every 2 weeks, 5 (9.1%) switched to 6 mg/kg once every 4 weeks, and 1 was up-titrated to 3 mg/kg once weekly.

The results showed that the model-based annualized bleed rate (ABR) for treated bleeds was 0.4 (95% confidence interval [CI], 0.30-0.63), with 54.5% of participants (n = 30) having zero treated bleeds. In addition, no intracranial hemorrhage (ICH) occurred in the patient group. For the 25 (45.5%) of patients who were treated for bleeds, all were traumatic. In terms of AEs, nine participants (16.4%) had ≥1 emicizumab-related AEs, and they were all grade 1 injection-site reactions. However, no AE led to treatment changes. There were no deaths, and no TEs or TMAs occurred. In addition, no participant tested positive for anti-emicizumab antibodies, and two participants were confirmed positive for FVIII inhibitors.

Overall, the findings from the HAVEN 7 trial demonstrated that emicizumab is efficacious and has a positive safety profile and is well-tolerated in infants with severe HA without FVIII inhibitors at a currently approved dose.

Reference

Pipe S, Collins P, Dhalluin C, et al. Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis of a phase 3b open-label trial. Blood. 2024;143(14):1355-1364. 10.1182/blood.2023021832