Vichinsky E, Hoppe CC, Ataga KI, et al. - Through a multicenter, phase 3, double-blind, randomized, placebo-controlled trial, researchers assessed the effectiveness and safety of two dose levels of voxelotor (1,500 mg and 900 mg, administered orally once daily) with placebo in 274 individuals with sickle cell disease. In the 1,500 mg voxelotor group vs the placebo group, a significantly greater percentage of individuals had a hemoglobin response. In both voxelotor dose groups vs those who were receiving a placebo, anemia worsened in fewer individuals between baseline and week 24. At week 24, in comparison to the placebo group, the 1,500 mg voxelotor group had significantly higher decreases from baseline in the indirect bilirubin level and percentage of reticulocytes. Among the trial groups, the proportion of individuals with an adverse event that happened or got worse during the treatment period was comparable. Adverse events of at least grade 3 occurred in 26%, 23%, and 26%, of the individuals in the 1,500 mg voxelotor group, 900 mg voxelotor group, and in the placebo group, respectively; researchers concluded most were not associated with the trial drug or placebo. In conclusion, hemoglobin levels were significantly improved and markers of hemolysis were significantly decreased by voxelotor. These conclusions were constant with the inhibition of deoxygenated sickle hemoglobin polymerization and shows disease-modifying possibilities.