Children aged 2 to less than 4 years with sickle cell disease (SCD) demonstrated increased hemoglobin levels and a decrease in hemolysis markers after treatment with voxelotor in the HOPE-KIDS 1 trial.
Voxelotor is already approved by the United States Food and Drug Administration for the treatment of SCD among children aged 4 or older. A poster presented at the 2023 ASPHO Annual Meeting reported results from the part D portion of the phase 2a HOPE-KIDS 1 trial (ClinicalTrials.gov Identifier: NCT02850406). Results from the part C portion of children aged 4 to younger than 12 were reported previously and were consistent with findings from the pivotal trial among patients aged 12 or older.
Part D of the open-label trial treated 23 children aged 2 to less than 4 years with SCD with weight-based equivalent dose of voxelotor of 1500 mg/day for up to 48 weeks. Voxelotor is given as an oral suspension or in dispersible tablets. The primary endpoints were treatment-emergent adverse events (TEAEs) and serious AEs. Secondary endpoints included change from baseline at 24 weeks in hemoglobin levels and markers of hemolysis.
At baseline, the median age at was 2.0 years, 60.9% of patients were male, and 39.1% of patients were Black or African American, 39.1% were White, and 21.7% were Middle Eastern or North African. HbSS was the most common SCD genotype, which was present among 82.6% of patients. The mean baseline hemoglobin was 8.4 g/dL, the mean fetal hemoglobin was 19.4%, and the mean white blood cell count was 10.9 x 109 /L. There were 69.6% of patients currently treated with hydroxyurea and concurrent hydroxyurea was allowed during the study.
TRAEs were reported among 91.3% of patients, including 42.9% that were grade 3, 28.6% that were grade 2, and 28.6% that were grade 1. There were no grade 4 or 5 events. The rate of serious AEs was 47.8%, with the most common being anemia and pyrexia. Treatment-related AEs that were unrelated to SCD occurred among 13.0% of patients, none of which were serious.
Of the 20 patients evaluable for efficacy at 24 weeks, the mean increase in hemoglobin from baseline was 0.6 g/dL. There were 45.0% of patients who demonstrated a hemoglobin response that was greater than 1 g/dL. Throughout the study, there were 75.0% of patients who achieved a hemoglobin response of greater than 1 g/dL at some point.
All markers of hemolysis decreased by 24 weeks. Indirect bilirubin decreased by 24.5%, reticulocytes by 3.65%, and lactate dehydrogenase by 0.4%.
The authors concluded that these findings were consistent with the results from part C of the same study and the pivotal HOPE trial in older age groups, “providing support for the use of voxelotor as a potential strategy for early mitigation of hemolysis and anemia in children with SCD aged 2 to less than 4 years.”
Disclosures: This research was supported by Pfizer. Please see the original reference for a full list of disclosures.
Fuh B, Inati A, Inusa BPD, et al. Interim safety and efficacy of voxelotor in children aged 2 to <4 years with sickle cell disease. ASPHO 2023; May 10-13, 2023. Abstract 378.