FDA Approves Voxelotor for Sickle Cell Disease

The FDA has approved voxelotor, a once-daily oral therapy that modulates hemoglobin affinity for oxygen by binding to hemoglobin S and stabilizing it, to treat patients with sickle cell disease (SCD) aged 12 and older. Voxelotor inhibits hemoglobin polymerization, reduces sickling and improves red blood cell survival.

This approval is based on results from the phase III HOPE trial, in which 274 patients were randomized to receive either:

  • voxelotor 1,500 mg (n=90)
  • voxelotor 900 mg (n=92)
  • placebo (n=92)

The median age of participants was 24 years (range = 12-64) and baseline hemoglobin (Hb) range was 5.5 to 10.5 g/dL. Approximately 65% of enrolled patients were taking hydroxyurea at the time of enrollment; those on stable hydroxyurea doses continued therapy throughout the trial.

The primary endpoint of the study was Hb response rate, defined as an increase of >1 g/dL from baseline to week 24. For voxelotor, the response rate was 51% (n=46/90) compared with 6.5% (n=6/92) for the placebo group (p<0.0001). In the arm receiving 1,500 mg voxelotor, the mean changes for Hb, indirect bilirubin, and reticulocyte count were 1.14 g/dL, -29.08%, and -19.93% respectively, compared with -0.08 g/dL, -3.16%, and 4.54% in the placebo group.

Adverse events that occurred in >10% of patients include headache, diarrhea, abdominal pain, nausea, rash, fatigue, and pyrexia. The recommended starting dosage is 1,500 mg orally once daily.

Source: FDA press release, November 25, 2019.