Emicizumab Prophylaxis for the Treatment of Infants with Severe Haemophilia A without Factor VIII Inhibitors: Primary Analysis of the HAVEN 7 Study
Bildiriler > Tam Metin Bildiri
Yazarlar: J. Oldenburg, S. W. Pipe, P. Collins, C. Dhalluin, G. Kenet, C. Schmitt, M. Buri, V. Jiménez-Yuste, F. Peyvandi, G. Young, M. E. Mancuso, K. Kavakli, A. Kiialainen, M. Niggli, T. Chang, M. Lehle, K. Fijnvandraat
Hämostaseologie, , , Uluslararası, Tam Metin Bildiri, Wos
Özet
Introduction Venous access presents a significant challenge in infants with haemophilia A (IwHA) requiring prophylaxis.Subcutaneous emicizumab enables prophylaxis from birth, reducing bleed risk. The HAVEN 7 (NCT04431726) primary analysis evaluates emicizumab prophylaxis over≥52 weeks (wks) in IwHA. Method IwHA in the Phase 3b, open-label study were aged≤12 months (m) without factor (F)VIII inhibitors. They received emicizumab 3mg/kg maintenance dose every 2wks (Q2W) for 52wks, continuing emicizumab for 7 years’ planned follow-up. Endpoints include efficacy (negative binomial regression model-based annualised bleed rates [ABR] for treated, all, treated spontaneous, and treated joint bleeds), safety, pharmacokinetics, anti-emicizumab antibodies (ADAs), FVIII inhibitors, and biomarkers (biomarker results are not detailed here, but will be included in the event of an associated presentation). Results At data cut-off (22 May, 2023),55 male IwHA had received emicizumab for≥52wks (54.5% previously minimally treated [≤5 exposure days, EDs], and 45.5% previously untreated [PUP]). Median (range) age: 4m (9 days–11m 30 days) at enrolment; 29 (12–39) m at cut-off. Median (range) treatment duration: 100.3 (52–118) wks. Mean ABRs (95% confidence interval) for treated, all, and treated joint bleeds were 0.4 (0.30–0.63), 2.0 (1.49–2.66), and 0.0 (0.01–0.09), respectively. Overall, 207 bleeds occurred in 46 IwHA (83.6%), 87.9% of which were traumatic. Of the 207 total bleeds, 42 bleeds in 25 IwHA were treated, all traumatic. Thirty (54.5%) IwHA had zero treated bleeds, and no IwHA had>3 treated bleeds. No intracranial haemorrhage occurred. One IwHA was up-titrated (Day 374) to 3mg/kg weekly per investigator request based on locally assessed decreasing emicizumab levels. Nine IwHA (16.4%) had≥1 treatment-related adverse event (AE), all Grade 1 injection-site reaction. No AE led to emicizumab change/withdrawal. No deaths/thrombotic events/thrombotic microangiopathies occurred. Mean steady-state emicizumab concentrations were 57–66µg/mL, above those with the same regimen in HAVEN 2/3 (46–48µg/mL). No IwHA developed ADAs. Two PUPs developed confirmed inhibitors after three and ten FVIII EDs, respectively. Conclusion This analysis suggests that emicizumab is efficacious and well tolerated in IwHA without FVIII inhibitors. Publication History Article published online: 26 February 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany