Sickle Cell Drug Voxelotor Withdrawn from Market Over Safety Concerns

Based on safety concerns,the manufacturer of voxelotor, a hemoglobin S polymerization inhibitor approved by the FDA for the treatment of sickle cell disease, has voluntarily withdrawn it from the market.

The FDA announced this action in an alert aimed at patients, caregivers, and health care professionals. The agency advised health care professionals to stop prescribing voxelotor and said that patients and caregivers should contact their health care professional about stopping voxelotor and starting another treatment option.

Pfizer, the drug’s manufacturer, is stopping distribution and discontinuing all active clinical trials and expanded access programs for voxelotor, because recent data indicate that the drug’s benefit "does not outweigh the risks for the sickle cell patient population," the FDA stated.

In postmarketing clinical trials of voxelotor, "a higher rate of vaso-occlusive crisis (severe pain caused by sickled red blood cells blocking blood flow and oxygen delivery to tissues) was reported in patients with sickle cell disease receiving [voxelotor] compared to placeb," the agency reported. In addition, more deaths occurred in the voxelotor treatment group than the placebo group in these studies. A higher rate of vaso-occlusive crisis in patients with sickle cell disease receiving voxelotor was also seen in two real-world registry studies.

The FDA has been conducting a safety review of the postmarketing clinical trial data for voxelotor and the real-world registry studies, as well as postmarketing data from the FDA Adverse Event Reporting System (FAERS). Once this safety review is completed, the FDA will communicate any additional findings, if necessary.

In 2019, the FDA approved voxelotor under the Accelerated Approval pathway for the treatment of sickle cell disease in adults and pediatric patients ages 12 and older. In 2021, the agency granted accelerated approval of voxelotor to treat sickle cell disease in patients 4 to 11 years of age.

The drug’s current label is here.

The FDA explained, "Accelerated approval is based on a surrogate or intermediate clinical endpoint that is reasonably likely to predict clinical benefit, allowing for earlier approval of drugs that treat serious conditions and fill an unmet medical need." After granting Accelerated Approval, the FDA typically requires postmarketing studies to verify and describe the medication’s clinical benefit.

Finally, the FDA stated that it "understands the importance of having safe and effective medications available to improve the health of patients living with this rare, serious disease. There are other FDA-approved medications for the treatment of sickle cell disease, which health care professionals may prescribe as an alternative treatment" to voxelotor.

Voxelotor is marketed by Pfizer Inc. as Oxbryta.