TY - JOUR
T1 - Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7)
T2 - primary analysis of a phase 3b, open-label trial
AU - Pipe, Steven W
AU - Collins, Peter W
AU - Dhalluin, Christophe
AU - Kenet, Gili
AU - Schmitt, Christophe
AU - Buri, Muriel
AU - Jiménez-Yuste, Victor
AU - Peyvandi, Flora
AU - Young, Guy
AU - Oldenburg, Johannes
AU - Mancuso, Maria Elisa
AU - Kavakli, Kaan
AU - Kiialainen, Anna
AU - Deb, Sonia
AU - Niggli, Markus
AU - Chang, Tiffany
AU - Lehle, Michaela
AU - Fijnvandraat, Karin
N1 - Copyright © 2023 American Society of Hematology.
PY - 2023/12/21
Y1 - 2023/12/21
N2 - 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.
AB - 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.
U2 - https://doi.org/10.1182/blood.2023021832
DO - https://doi.org/10.1182/blood.2023021832
M3 - Article
C2 - 38127586
SN - 0006-4971
JO - Blood
JF - Blood
ER -