Real-World Experience of Individuals with Sickle Cell Disease Treated with Voxelotor: Initial Report from the Multicenter, Prospective Prospect Study

Introduction: Sickle cell disease (SCD) is an inherited blood disorder in which sickle hemoglobin (HbS) polymerization results in red blood cell sickling, which in turn leads to chronic hemolytic anemia, unpredictable pain episodes, and recurrent vaso-occlusive crises (VOCs). Hemolysis and low hemoglobin (Hb) are associated with organ damage, increased morbidity, and early mortality. Voxelotor, a first-in-class HbS polymerization inhibitor, is approved in the US for the treatment of patients with SCD aged ≥4 years and in Europe for the treatment of hemolytic anemia due to SCD in patients aged ≥12 years. In the phase 3, randomized, controlled HOPE (NCT03036813) and the phase 2, open-label HOPE-KIDS 1 (NCT02850406) trials, patients treated with once daily oral voxelotor experienced increased Hb levels and reductions in markers of hemolysis at Week 24 compared with baseline. Here we report the first efficacy and safety data from patients with SCD enrolled in the prospective PROSPECT registry who received voxelotor in a real-world setting. Methods: PROSPECT (NCT04930445) is a post-marketing, open-label, observational, prospective patient registry of patients with SCD (aged ≥4 years) in the US. Eligible participants are being treated with voxelotor as prescribed by their physician as part of their usual care. Participants are treated and evaluated per standard of care and at the physician's discretion. Treatment, including interruptions and restarting treatment, continue at the discretion of the treating physician. Patients receive any additional medications or transfusions as determined and prescribed by their physician. Follow-up duration is 5 years after the first dose of voxelotor therapy. Study data are collected from patient medical records and secondary data sources and entered in case report forms via an electronic data capture system. Results: At data cutoff (May 30, 2023), 85 patients were enrolled at 5 sites. The mean (SD) age was 33.2 (15.3) years, 51.8% of patients were female, and most (92.9%) were Black or African American. Overall, 72.9% of patients were genotype HbSS, 62.4% were taking concurrent hydroxyurea, and mean (SD) Hb at baseline was 7.7 (1.53) g/dL. The mean (SD) duration of treatment, excluding gaps, was 47.0 (12.35) weeks. At the data cutoff, 76 patients (89.4%) continued voxelotor treatment; 7 patients (8.2%) never started voxelotor, and 2 patients (2.4%) discontinued treatment because of adverse events (AEs).The initial prescribed