EHA: Voxelotor for Sickle Cell Disease Has Disease-Modifying Potential

Research presented at the European Hematology Association 24th Congress found that voxelotor significantly increased hemoglobin levels and reduced markers of hemolysis in patients with sickle cell disease (SCD). The novel drug targets the core mechanisms behind SCD, and the findings “indicate a disease-modifying potential,” the authors noted. The results of the study were also published in The New England Journal of Medicine.

Voxelotor is a first-in-class, once-daily, oral hemoglobin-oxygen affinity modulator that targets red cell polymerization, the hemolytic anemia that can lead to chronic organ damage, stroke, and premature death.

The multicenter, double-blind, randomized, placebo-controlled, phase III HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS Polymerization) study randomized 274 patients (mean age = 25 years; range = 12-59 years) 1:1:1 to receive voxelotor 1,500 mg (n=90), voxelotor 900 mg (n=92), or placebo (n=92) for at least 24 weeks.

Improved hemoglobin with voxelotor

At week 24, the proportion of patients with a greater than 1.0 g/dL increase in hemoglobin from baseline (primary endpoint) was significantly higher among those treated with voxelotor 1,500 mg (59.5%; P<0.001) and 900 mg (38%; P<0.001) compared with placebo (9.2%).

There was a 29.1% reduction in indirect bilirubin in the voxelotor 1,500 mg group and a 20.3% reduction in the voxelotor 900 mg group versus a 3.2% reduction in the placebo group. In addition, the reduction in reticulocytes was 19.9% in the voxelotor 1,500 mg group and 1.3% in the voxelotor 900 mg group, while this increased by 4.5% in the placebo group.

The percentage of patients with an adverse event (AE) that occurred or worsened during treatment was similar across the groups. The most common AEs were headache and diarrhea. AEs of at least grade 3 occurred in 26% of the those receiving voxelotor 1,5000 mg, 23% in those receiving voxelotor 900 mg, and 26% of those in the placebo group. Most AEs were not related to treatment, according to the study.