Safety and efficacy of long‐term emicizumab prophylaxis in hemophilia A with factor VIII inhibitors: A phase 3b, multicenter, single‐arm study (STASEY)

Background: The bispecific monoclonal antibody emicizumab bridges activated factor IX and factor X, mimicking the cofactor function of activated factor VIII (FVIII), restoring hemostasis. Objectives: The Phase 3b STASEY study was designed to assess the safety of emicizumab prophylaxis in people with hemophilia A (HA) with FVIII inhibitors. Methods: People with HA received 3 mg/kg emicizumab once weekly (QW) for 4 weeks followed by 1.5 mg/kg QW for 2 years. The primary objective was the safety of emicizumab prophylaxis, including incidence and severity of adverse events (AEs) and AEs of special interest (thrombotic events [TEs] and thrombotic microangiopathies). Secondary objectives included efficacy (annualized bleed rates [ABRs]). Results: Overall, 195 participants were enrolled; 193 received emicizumab. The median (range) duration of exposure was 103.1 (1.1-108.3) weeks. Seven (3.6%) participants discontinued emicizumab. The most common AEs were arthralgia (n = 33, 17.1%) and nasopharyngitis (n = 30, 15.5%). The most common treatment-related AE was injection-site reaction (n = 19, 9.8%). Two fatalities were reported (polytrauma with fatal head injuries and abdominal compartment syndrome); both were deemed unrelated to emicizumab by study investigators. Two TEs occurred (myocardial infarction and localized clot following tooth extraction), also deemed unrelated to emicizumab. The negative binomial regression model-based ABR (95% confidence interval) for treated bleeds was 0.5 (0.27-0.89). Overall, 161 participants (82.6%) had zero treated bleeds. Conclusions: The safety profile of emicizumab prophylaxis was confirmed in a large population of people with HA with FVIII inhibitors and no new safety signals occurred. The majority of participants had zero treated bleeds.