Abstract Presentation Date: 6/9/2024 Presentation Start Time: 1:33:00 PM Background In patients with sickle cell disease (SCD), polymerization of sickle hemoglobin (HbS) results in red blood cell sickling and leads to hemolysis, chronic anemia, and vaso-occlusive crises. Voxelotor, a first-in-class HbS polymerization inhibitor, is approved in the United States and Europe for the treatment of patients with SCD aged ≥4 years and ≥12 years, respectively. To assess the safety and efficacy of long-term voxelotor use, we report an updated interim analysis of an open-label extension (OLE) of the HOPE phase 3 trial (NCT03036813). Methods Patients who completed the HOPE trial were eligible to enroll in the multicenter, global OLE study (NCT03573882) and received ongoing treatment consisting of once daily voxelotor 1500 mg if they continued to derive clinical benefit. Adverse event (AE) data were collected through 28 days after voxelotor discontinuation, and measurements of hemoglobin and clinical markers of hemolysis were summarized through 168 weeks of treatment in the OLE. Data are based on an interim data cut (December 31, 2022). Results Of 199 patients who completed the HOPE trial, 178 (89.4%) were enrolled and dosed in the OLE. Median age at enrollment was 25 years. The median duration of voxelotor exposure in the OLE was 124.0 weeks, and 81 patients were treated for ≥168 weeks. Of these, 52 had received voxelotor in the HOPE trial, for a combined duration of exposure of ≥ 240 weeks. Patients previously treated with placebo in the HOPE trial had a mean (SD) hemoglobin change from baseline (start of OLE) of 1.1 (1.51) g/dL at Week 168. The mean (SD) hemoglobin change from baseline for patients who previously received voxelotor 1500 mg was 0.5 (1.49) g/dL (n = 18), indicating durability of response with continued treatment. Markers of hemolysis (indirect bilirubin, reticulocyte percentage) improved in patients who received placebo in the HOPE trial and were stable for patients who previously received 1500 mg voxelotor in the HOPE trial. Non-SCD-related treatment-emergent AEs (TEAEs) were reported in 88.2% of patients; no new safety signals were identified. Most TEAEs were grade 1 or 2 in severity. Eight deaths occurred, none deemed related to voxelotor treatment. Conclusions In this updated analysis from the HOPE OLE, long-term use of voxelotor was effective at improving hemoglobin and clinical markers of hemolysis in patients with SCD. The safety profile in the OLE was consistent with findings from the HOPE trial, and no new safety signals were identified with exposure through a combined 240 weeks of treatment. © American Society of Hematology (2023). Reused with permission.

Over 4 Years of Safety and Efficacy with Voxelotor in Patients with Sickle Cell Disease