Phase III HOPE Study of GBT 440 met primary endpoint in sickle cell disease

Global Blood Therapeutics announced new results from its Phase III HOPE Study of GBT 440 (voxelotor) in patients ages 12 and older with sickle cell disease (SCD). The findings from 274 adolescents and adults treated with voxelotor showed the HOPE Study met its primary endpoint of an improvement in hemoglobin greater than 1 g/dL at 24 weeks with voxelotor 1500 mg compared with placebo, with a favorable safety and tolerability profile. In the study, voxelotor provided a rapid, statistically significant and sustained improvement in hemoglobin levels and reduced the incidence of worsening anemia and hemolysis.

The ITT analysis of all 274 patients at 24 weeks showed that hemoglobin improved rapidly from baseline to the earliest timepoint measured (2 weeks) with voxelotor 1500 mg and was sustained through 24 weeks (p<0.001 vs. placebo). The improvement in hemoglobin was similar in patients with or without background use of hydroxyurea. Voxelotor 1500 mg increased hemoglobin levels to a mean of 9.8 g/dL at 24 weeks from a baseline of 8.6 g/dL, consistent with a clinically meaningful improvement in anemia.

In addition, it showed improvements from baseline in hemoglobin, percent reticulocytes and indirect bilirubin occurred with both voxelotor doses, further demonstrating an improvement in hemolysis consistent with a dose-related inhibition of hemoglobin polymerization. There were numerically fewer vaso-occlusive crises (VOCs) and a lower annualized incidence rate (per person-year) of VOCs in both voxelotor dose groups than in the placebo group, despite the significant increases in hemoglobin with voxelotor treatment. Finally, voxelotor was generally safe and well tolerated, with both doses having similar safety profiles. Treatment discontinuation rates did not differ substantially among the three trial groups. There was no evidence of impairment of tissue oxygenation at either dose of voxelotor. The data were published in The New England Journal of Medicine and featured at the 24th European Hematology Association (EHA) Congress.

See: "A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease" Elliott Vichinsky et al. NEJM June 14, 2019 DOI: 10.1056/NEJMoa1903212