On November 25, 2019, the Food and Drug Administration granted accelerated approval to voxelotor (Oxbryta, Global Blood Therapeutics) for adults and pediatric patients 12 years of age and older with sickle cell disease.
Efficacy was evaluated in 274 patients with sickle cell disease in HOPE (NCT 03036813), a randomized, double-blind, placebo-controlled, multicenter trial. Patients were randomized to voxelotor 1500 mg (N=90), 900 mg (N=92), or placebo (N=92). The median age was 24 years (range 12, 64). Approximately 65% of patients were taking hydroxyurea at trial entry. Patients were enrolled if their baseline hemoglobin (Hb) ≥5.5 to ≤10.5 g/dL. Patients on stable hydroxyurea doses continued the drug throughout the trial. Randomization was stratified by whether the patient was already receiving hydroxyurea, by geographic region, and by age.
The primary efficacy outcome measure was Hb response rate defined as an Hb increase of >1 g/dL from baseline to week 24. The response rate for voxelotor was 51.1% (46/90) compared to 6.5% (6/92) in the placebo group (p<0.0001). Additional efficacy evaluation included change in Hb, percent change in indirect bilirubin and percent reticulocyte count during this time period. In the voxelotor 1,500 mg group, the mean change for Hb, indirect bilirubin, and percent reticulocyte count were 1.14g/dL, ‑29.08%, and -19.93%, respectively. In the placebo group, the mean change during this time period for Hb, indirect bilirubin, and percent reticulocyte count were ‑0.08g/dL, ‑3.16%, and 4.54%, respectively.
The most common adverse reactions (>10%) to voxelotor are headache, diarrhea, abdominal pain, nausea, rash, fatigue and pyrexia. Product information includes a warning for hypersensitivity and potential laboratory interference. Voxelotor may interfere with measurement of Hb subtypes (HbA, HbS, and HbF) by high performance liquid chromatography.
The recommended voxelotor dose is 1500 mg orally once daily with or without food.
This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). FDA granted this application priority review, fast track, and Breakthrough Therapy designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
