Abstract Number: PB0957
Meeting: ISTH 2020 Congress
Background: Emicizumab bridges activated factor IX (FIXa) and FX to restore hemostasis in persons with hemophilia A (PwHA), and is widely approved for prophylaxis in PwHA with/without FVIII inhibitors.
Aims: To present the efficacy, safety and pharmacokinetics of emicizumab from the Phase III HAVEN 5 (NCT03315455) trial in PwHA in the Asia-Pacific region.
Methods: Following informed consent and ethics committee approval, PwHA (≥12 years, with/without FVIII inhibitors) were randomized 2:2:1 to receive subcutaneous (SC) emicizumab prophylaxis: 1.5 mg/kg once-weekly (QW), Arm A; 6 mg/kg once every four weeks (Q4W), Arm B, or; no prophylaxis, Arm C. Loading doses were administered for the first four weeks (3 mg/kg QW SC emicizumab; Arms A and B). The primary endpoint was annualized bleeding rate (ABR) for treated bleeds, calculated using a negative binomial-regression model. Secondary endpoints included additional bleeding-related endpoints, adverse events (AEs) and pharmacokinetic analyses.
Results: At clinical cut-off (06/21/2019), 70 participants aged 12-66 (median 29.0) years were enrolled and had completed 24 weeks of treatment. Significant reductions in treated bleed ABRs of 96% were observed with emicizumab prophylaxis (Arm: A, 1.0; B, 1.0) versus no prophylaxis (Arm C, 27.0; p< 0.0001; Table 1). In Arms A and B, 65.5% (19/29) and 55.6% (15/27) of participants had zero treated bleeds respectively, versus 7.1% (1/14) of participants in Arm C. Efficacious mean emicizumab trough plasma concentrations >30 µg/mL were sustained from Week 5. Emicizumab was well tolerated; the most common AEs were upper respiratory tract infection (Arm: A, 31.0%; B, 18.5%; C, 14.3%) and injection site reaction (Arm: A, 13.8%; B, 18.5%; C, 0.0%). No fatalities, thrombotic microangiopathies or thrombotic events were reported. Eight participants developed treatment-induced anti-drug antibodies; one with transient neutralizing potential.
Conclusions: Emicizumab QW or Q4W prophylaxis offers a highly efficacious, well tolerated, flexible option for PwHA from the Asia-Pacific region.
To cite this abstract in AMA style:Wang S, Zhao X, Wang X, Sun J, Chuansumrit A, Zhou J, Li L, Hsu W, Xu J, Barrington P, Yang R. A Randomized, Multicenter, Open-label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus No Prophylaxis in Persons with Hemophilia A in the Asia-Pacific region (HAVEN 5) [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/a-randomized-multicenter-open-label-phase-iii-clinical-trial-to-evaluate-the-efficacy-safety-and-pharmacokinetics-of-prophylactic-emicizumab-versus-no-prophylaxis-in-persons-with-hemophilia-a-in/. Accessed May 6, 2021.
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