FDA Approves Novel Sickle Cell Disease Treatment Voxelotor

The FDA Monday granted accelerated approval to voxelotor (Oxbryta) for the treatment of sickle cell disease (SCD) in adults and pediatric patients 12 years of age and older.

Voxelotor, a polymerization inhibitor, has a novel mechanism of action. The first-in-class therapy regulates the affinity of hemoglobin (Hb) for oxygen, resulting in a decrease in the concentration of deoxygenated sickle hemoglobin (HbS), which forms polymers. It’s hypothesized that because oxygenated HbS cannot polymerize, modifying HbS to increase the proportion of oxygenated to deoxygenated HbS in red blood cells would alter disease severity.

In sickle cell disease, a lifelong, inherited blood disorder, red blood cells are abnormally shaped (a "sickle" shape), restricts the blood flow and limiting oxygen delivery to the body’s tissues, leading to severe pain and organ damage. It is also characterized by severe and chronic inflammation that worsens vaso-occlusive crises during which patients experience episodes of extreme pain and organ damage.

Nonclinical studies demonstrated that voxelotor inhibits red blood cell sickling, improves red blood cell deformability and improves the blood’s ability to flow.

The approval was based on the results of a clinical trial with 274 patients with SCD. In the study, 90 patients received 1500 mg of voxelotor, 92 patients received 900 mg of voxelotor, and 92 patients received a placebo. Effectiveness was based on an increase in hemoglobin response rate in patients who received 1500 mg of voxelotor, which was 51.1% for these patients compared to 6.5% in the placebo group.

The drug was granted Accelerated Approval under a Fast Track designation and also received Orphan Drug designation. The FDA granted the approval of voxelotor to Global Blood Therapeutics. Further clinical trials are required to verify and describe voxelotor Oxbryta’s clinical benefit.

Common side effects for patients were headache, diarrhea, abdominal pain, nausea, fatigue, rash, and pyrexia.