Researchers demonstrated the effectiveness and safety of 1500 mg as a therapeutic dose of voxelotor in adults and adolescents with sickle cell disease (SCD) and published their results in CPT Pharmacometrics Systems in Pharmacology. The study revealed a persistent effect of the medication for up to 72 weeks of therapy.

“Significant relationships between voxelotor concentration and clinical measures of anemia and hemolysis confirm the 1500 mg q.d. dose compared to 900 mg,” the authors wrote. “The significant relationship between change in hemoglobin with hemolysis improvements supports the voxelotor mechanism of action.”

The research team conducted an analysis of voxelotor exposure-response, clinical anemia, hemolysis measurements, and adverse events in a patient cohort ≥12 years of age over a period of 72 weeks. Data from 2 clinical trials of voxelotor, the HOPE Kids 1 trial, and the HOPE trial, were included.

They achieved the target goal of a 1 g/dl increase in hemoglobin (Hb) at the therapeutic voxelotor dose of 1500 mg and observed improved measures of hemolysis as well as a linear increase in Hb from baseline with increased voxelotor serum concentrations. The benefits and safety profile of voxelotor were comparable between the adult and adolescent patients.

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Adverse events were mostly graded 1 and included increased alanine aminotransferase and reduced white blood cell counts. No clinically important safety risks were observed for doses between 900 mg and 1500 mg.

At 72 weeks, greater improvements in measures of hemolysis and anemia with the 1500 mg dose support the higher dose over 900 mg, however, the authors caution that higher doses might lead to a higher rate of adverse events and therefore patients undergoing dose increases should be monitored closely.

Reference

Green ML, Savic RM, Tonda M, et al. Model-informed drug development of voxelotor in sickle cell disease: exposure-response analysis to support dosing and confirm mechanism of action. CPT Pharmacometrics Syst Pharmacol. Published online April 21, 2022. doi:10.1002/psp4.12780