Safety and effectiveness of voxelotor in individuals with sickle cell disease in the RETRO and PROSPECT US registries

Two registry studies, RETRO and PROSPECT, were conducted to evaluate real-world effectiveness and safety outcomes in US participants with sickle cell disease (SCD) who received voxelotor as standard of care. RETRO collected retrospective data of participants aged ≥12 years at 9 US sites for ~1 year after voxelotor initiation. PROSPECT collected retrospective and prospective data of participants aged ≥4 years at 24 US sites, with 5-years planned follow-up. Both studies collected data for 1-year pre-voxelotor initiation. RETRO enrolled 216 participants. PROSPECT enrolled 265 participants before voxelotor was withdrawn from global markets in September 2024; of these, 260 participants received voxelotor. The mean±SD duration of voxelotor treatment was 50.52±25.1 and 143.2±65.6 weeks in RETRO and PROSPECT, respectively. Safety analyses included all participants who received voxelotor. Mean±SD observed change in hemoglobin from baseline was from 0.6±1.6 to 0.8±1.5 g/dL in RETRO (~1-year) and from 0.1±1.7 to 0.7 ±1.5 g/dL in PROSPECT (54 months). Decreases from baseline in hemolysis markers (absolute/percentage reticulocyte counts, total/indirect bilirubin) post-voxelotor were observed across all time points in RETRO and across most time points in PROSPECT. Acute pain crisis (APC) was the most common SCD complication, with annualized incidence rates (total number of events/total patient-years) pre- and post-voxelotor of 1.33 and 1.54 in RETRO and 4.78 and 3.15 in PROSPECT. No new safety findings were identified. Despite inherent limitations of registry studies, voxelotor treatment increased hemoglobin and decreased hemolysis markers in US clinical practice, with no evidence of an increased frequency of APC.