Efficacy of emicizumab is maintained throughout dosing intervals for bleed prophylaxis

Authors: Pipe, SW.; Trzaskoma, B; Minhas, M; Lehle, M; Ko, RH.; Gao, L; Mahlangu, J; Kempton, CL.; Kessler, CM.; Kruse-Jarres, R.

Affiliations: Univ Michigan, Dept Pediat, Ann Arbor, MI USA. Michigan, Dept Pathol, Ann Arbor, MI USA. Inc, US Med Affairs, San Francisco, CA USA. F Hoffmann La Roche Ltd, Prod Dev, Basel, Switzerland. Analystat Corp, Point Roberts, WA USA. Univ Witwatersrand, Sch Pathol, Dept Mol Med & Haematol, Fac Hlth Sci, Johannesburg, South Africa. Natl Hlth Lab Serv, Johannesburg, South Africa. Emory Univ, Dept Hematol & Med Oncol, Sch Med, Atlanta, GA USA. Emory Univ, Hemophilia Georgia Ctr Bleeding & Clotting Disord, Sch Med, Atlanta, GA USA. Georgetown Univ, Div Coagulat, Sch Med, Washington, DC USA. Univ Washington, Div Hematol, Seattle, WA USA. Washington Ctr Bleeding Disorders, Seattle, WA USA.

Publication: Research and Practice in Thrombosis and Haemostasis. 2023. 7

ABSTRACT: BACKGROUND: Across the HAVEN clinical trial program, the efficacy of emicizumab has been demonstrated in children, adolescents, and adults with hemophilia A, with or without factor VIII inhibitors. After the 4-week loading dose period, emicizumab concentrations are expected to remain at levels that provide bleed protection throughout the entire dosing interval, regardless of the chosen maintenance dosing regimen, ie, weekly, every 2 weeks, or every 4 weeks. OBJECTIVES: The objective of this study was to examine the timing of treated bleeds within the dosing intervals for emicizumab administered during the HAVEN 1 to 4 studies. METHODS: In this post hoc analysis, we pooled data from all the participants of the HAVEN 1 to 4 studies and analyzed the timing of treated bleeds in relation to the emicizumab dose. RESULTS: A total of 392 participants were included in this analysis, with a median (range) age of 28.0 years (1.1-77.0 years). Target joints were identified in 237 of 392 (60.5%) participants before the study entry. Overall, 211 of 392 (53.8%) participants experienced 907 treated bleeding events. The total mean (SD) annualized bleeding rate across the 4 studies was 1.6 (5.9). There was no evidence that bleeding events clustered on any 1 particular day in any dosing schedule from HAVEN 1 to 4 (P >.05 for all 3 treatment regimens). CONCLUSION: Data from the HAVEN 1 to 4 trials show consistent bleed prevention within the dosing interval, regardless of the dosing regimen chosen. These findings provide further evidence of the sustained efficacy of emicizumab across all approved dosing regimens to reduce bleeding in people with hemophilia A.