P1432: patterns of voxelotor use in a multicenter, real-world study of patients with sickle cell disease

Topic: 26. Sickle cell disease Background: Sickle cell disease (SCD) is an inherited disorder driven by polymerization of deoxygenated sickle hemoglobin (HbS). Polymerized HbS causes red blood cell (RBC) sickling, which leads to chronic hemolytic anemia, painful vaso-occlusive crises (VOCs), and end-organ damage. Voxelotor is a HbS polymerization inhibitor approved in the US and UAE for patients aged ≥4 years and in the EU, Great Britain, Oman, and Kuwait in patients aged ≥12 years. In the pivotal HOPE trial, voxelotor increased hemoglobin and reduced hemolytic markers in patients with SCD. Real-world evidence with voxelotor is emerging; however, little information is available on real-world patterns of voxelotor use and its impacts on safety and effectiveness. Aims: To examine patterns of voxelotor use in patients from 9 clinical sites in the US as part of the Retrospective Real World Oxbryta Data Collection and Analysis Study (RETRO). Methods: RETRO (NCT04930328) is a postmarketing, multicenter, retrospective data collection and analysis study. Eligible patients were aged ≥12 years, were diagnosed with SCD (any genotype), had been receiving voxelotor for ≥2 consecutive weeks, and had laboratory and clinical data available from 1 year before and up to 1 year after their first voxelotor dose. As this study was a retrospective record review, institutional review boards issued informed consent waivers. Results: Data from 216 patients were collected and analyzed. Mean (SD) patient age was 33.5 (14.2) years, and 14.4% of patients were aged <18 years. A total of 120 patients (55.6%) were female, 189 (87.5%) were African American or Black, and 199 (92.1%) had the HbSS genotype. Sixty percent of patients were treated with voxelotor for ≥9 months during the 12-month study period. Most patients (86%) were prescribed an initial dose of 1500 mg once daily, and 14% were prescribed an initial dose lower than that recommended in the label. Twenty-three percent of patients had a physician-initiated dose modification. Treatment discontinuation was reported for 21.8% of patients; reasons included adverse events (8.3%) and “other” (13.5%), which included loss to follow-up, physician’s decision, and study withdrawal. Preliminary safety analyses suggest that there was no evidence of drug interruption or discontinuation leading to rapid onset of adverse events (including VOCs), as has been suggested previously for patients with severe SCD (Nagalapuram V, Am J Hematol; 2022). In the 45 patients (20.8%) who had a VOC after drug interruption or discontinuation, the median (25th to 75th percentile) time to onset of a VOC was 74 (29-138) days. Two patients had a VOC within 1 week of dose interruption or discontinuation; both events were deemed unrelated to voxelotor by investigators. These data align with preclinical findings suggesting that the impact of voxelotor on red cell rheology is acutely sustained after voxelotor dose interruption or discontinuation (Kanne CK et al, Front Physiol; 2021). Analyses are ongoing to further understand the effects of voxelotor dosing patterns on safety and effectiveness. Summary/Conclusion: RETRO is the largest multicenter study to retrospectively collect and analyze real-world data from voxelotor-treated patients with SCD. Most patients did not require dose modification or treatment discontinuation. Discontinuation and dose interruption were not found to be related to subsequent onset of VOCs. Data on patterns of voxelotor use in the real-world setting can provide valuable insights into the impacts of prescribing and dosing practices that are different from those on the label. Funding: Pfizer Inc. Keywords: Sickle cell disease, Sickle cell patient, Sickle cell anemia, Sickle cell