Abstract Number: PB0495
Meeting: ISTH 2021 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: Modelling indicates that body weight is an important predictor of emicizumab pharmacokinetics. In the HAVEN studies, actual weight-based dosing provided efficacious bleed prevention, but the impact of obesity (body mass index [BMI] ≥30 kg/m2) was not assessed.
Aims: To compare annualized bleed rate (ABR) and emicizumab trough concentrations among obese and non-obese adult persons with hemophilia A (PwHA) in HAVEN 1, 3, and 4 in a post-hoc analysis.
Methods: Informed consent and ethics committee approval were obtained before the HAVEN studies. Inclusion criteria for this analysis were: ≥18 years of age; with or without FVIII inhibitors; ≥24 weeks on emicizumab; baseline BMI available. Treated ABRs were analyzed across the study period (using negative binomial regression) and in 24‑week intervals (unadjusted) until up-titration for those who were up-titrated. Mean emicizumab trough plasma concentrations, measured at scheduled time points during each study, were analyzed.
Results: At database cut-off (15 May 2020), 44 (17%) and 216 (83%) adult PwHA with BMI ≥30 kg/m2 and BMI <30 kg/m2 were included and had 94.29 and 522.97 patient-years of emicizumab exposure, respectively. Across the study period, adjusted ABRs were 1.48 (95% confidence interval [CI]: 0.82–2.68) and 1.40 (95% CI: 1.06–1.85) for adults with BMI ≥30 kg/m2 and <30 kg/m2, respectively. ABRs were consistent across the two groups over time (Table 1). Efficacious trough concentrations were sustained in both groups regardless of dosing regimen, with concentrations >30 µg/mL. In the once weekly dosing cohort, mean (standard error) emicizumab trough concentration was 51.47 (3.04) µg/mL and 53.21 (1.18) µg/mL at Week 5 following loading dosing, for adults with BMI ≥30 kg/m2 (n=27) and <30 kg/m2 (n=137), respectively (Figure 1).
Conclusions: Efficacious emicizumab trough concentrations were maintained in obese and non‑obese PwHA in HAVEN 1, 3, and 4, and treated ABRs were similar in both groups.
Table 1: Unadjusted annualized bleed rates for treated bleeds among adult PwHA with and without FVIII inhibitors with measured baseline BMI and ≥24 weeks on emicizumab in HAVEN 1, HAVEN 3, or HAVEN 4, grouped by baseline BMI (≥30 kg/m2 or <30 kg/m2) over time (N=260)
Figure 1: Mean (standard error) emicizumab trough concentrations of PwHA with and without FVIII inhibitors with measured baseline weight and ≥24 weeks receiving emicizumab once weekly in HAVEN 1 or HAVEN 3, grouped by baseline BMI (≥30 kg/m2 or <30 kg/m2) over time (N=166)
To cite this abstract in AMA style:
Recht M, Mahlangu J, Minhas M, Trzaskoma B, Shah M, Young G. Emicizumab in Obese Adults with Hemophilia A – Pooled Data from Three Phase III Studies (HAVEN 1, 3 and 4) [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/emicizumab-in-obese-adults-with-hemophilia-a-pooled-data-from-three-phase-iii-studies-haven-1-3-and-4/. Accessed November 29, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/emicizumab-in-obese-adults-with-hemophilia-a-pooled-data-from-three-phase-iii-studies-haven-1-3-and-4/