5579775 OVERVIEW OF THE VOXELOTOR POST-APPROVAL CLINICAL RESEARCH PROGRAM

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Background: Voxelotor, a sickle hemoglobin polymerization inhibitor, is approved in the United States for the treatment of sickle cell disease (SCD) in adults and pediatric patients 4 years of age and older, and in the European Union, United Arab Emirates, Oman, and Great Britain for adult and pediatric patients 12 years of age and older. Efficacy and safety data from the randomized, placebo-controlled HOPE trial demonstrated the effectiveness and durability of voxelotor in increasing hemoglobin (Hb) levels and reducing markers of hemolysis in adults and adolescents. Support for the use of voxelotor in children aged 4 to <12 years was provided by the open-label HOPE-KIDS 1 trial. Due to its mechanism of action, voxelotor has the potential to alter disease pathogenesis and mitigate disease-associated morbidity and mortality. Further research is needed to more clearly understand the role of voxelotor in preventing complications of SCD, reducing healthcare utilization, and improving quality of life. Aims: To establish a more thorough understanding of the impact of voxelotor on SCD, a wide-ranging post-approval clinical research program is underway and described herein. Methods: Eight GBT-sponsored post-approval studies of voxelotor are either currently active or have completed, with results pending. Two observational studies, 1 retrospective (RETRO) and 1 prospective (PROSPECT), are evaluating the effect of voxelotor in real-world settings. ActIVe is an interventional, open-label, single-group study evaluating the effect of voxelotor on daily physical activity and sleep quality, as measured by a wrist-worn device, in patients with SCD and chronic, moderate anemia. HOPE-KIDS 1 Part D is an open-label, multiple-dose trial evaluating the safety, tolerability, and pharmacokinetics of voxelotor in infants and young children with SCD. The 4 remaining studies are randomized, placebo-controlled studies: RESOLVE is evaluating the effects of voxelotor on the resolution of leg ulcers in patients with SCD; the Neurocognitive Function study is assessing the treatment effects of voxelotor on neurocognitive function, as assessed by the National Institutes of Health Toolbox Cognition Module of executive abilities in children and adolescents with SCD; the Cerebral Hemodynamics study is evaluating the impact of voxelotor treatment on cerebral blood flow in adults and adolescents with SCD; and HOPE-KIDS 2 is a post-approval confirmatory study evaluating the effect of voxelotor on transcranial Doppler flow velocity in pediatric patients with SCD. An overview of patient populations, study arms, and key endpoints for each of the voxelotor post-approval studies is provided in the Table. Results: RETRO recently completed data collection, and analyses are currently underway. All other trials are ongoing, with results expected to be released in late 2022 through 2029. Summary/Conclusion: The current post-approval clinical research plan for voxelotor represents a methodologically diverse set of studies, mixing real-world evidence with randomized, controlled trials. The data generated from these studies are expected to further guide clinicians and patients regarding the clinical use of voxelotor for people with SCD.