Voxelotor for Sickle Cell Disease Recalled After Safety Concerns

Aida Habtezion, MD, MSc

Credit: PhRMA

Pfizer has announced the voluntary withdrawal of voxelotor (OXBRYTA) for the treatment of sickle cell disease (SCD) due to safety concerns after a review of clinical data revealed the overall benefits of the drug no longer outweigh the risks.¹

Announced by Pfizer on September 25, 2024, the voxelotor recall affects all markets where the drug is approved, and all active voxelotor clinical trials and global expanded access programs will be discontinued. Pfizer plans to investigate the available data and inform patients, regulatory authorities, investigators, and clinicians about the actions and appropriate next steps for voxelotor.

“Our primary concern is for patients who suffer from SCD, which remains a very serious and difficult-to-treat disease with limited treatment options,” said Aida Habtezion, MD, MSc, chief medical officer and head of worldwide medical and safety at Pfizer. “We advise patients to contact their physicians to discuss alternative treatments while we continue to investigate the findings from our review of the data.”

The decision was based on the totality of clinical data demonstrating the overall benefit of voxelotor did not overcome the risks for a population with SCD, due to an imbalance in vaso-occlusive crises (VOCs) and fatal events. Postmarketing clinical trials showed a higher rate of VOCs in patients treated with voxelotor, compared with placebo, as well as an increase in deaths. Two real-world registry-based studies also showed a higher rate of VOCs in patients with SCD treated with voxelotor.

The US Food and Drug Administration (FDA) announced their safety review of the postmarketing clinical trial data for voxelotor, the real-world registry studies, and postmarketing data from the FDA Adverse Event Reporting System (FAERS).² The announcement indicated the agency would communicate any additional safety findings, if necessary.

“FDA understands the importance of having safe and effective medications available to improve the health of patients living with this rare, serious disease,” the agency stated.² “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.

The European Medicines Agency (EMA) human medicines committee announced a parallel recommendation to suspend the marketing authorization for voxelotor.³ Since July 2024, the EMA had been reviewing the benefits and risks of voxelotor after identifying a higher-than-anticipated number of deaths in treated patients with SCD.

Both agencies urged healthcare professionals to halt the prescription of voxelotor and patients and caregivers to contact their healthcare professionals about starting another treatment option.

A statement from the National Alliance of Sickle Cell Centers (NASCC) called the news “disappointing” for many, but an opportunity to determine the risks of voxelotor and learn how to better optimize medications for SCD in the future.⁴ They urged all patients with SCD to make an appointment with their doctor and work out a weaning plan with the care team.

“Don’t lose faith–this is a step backward but we will stay on the path to better outcomes for everyone,” the statement added.⁴

The FDA approved voxelotor under the accelerated approval pathway in 2019 for adults and children aged ≥12 years with SCD, with subsequent accelerated approval in 2021 for children aged 4–11 years.¹ Accelerated approval under this program allows for earlier approval of drugs that fill an unmet medical need, but require postmarketing studies to verify the clinical benefit of these medications.

References

1. _{Pfizer Voluntarily Withdraws All Lots of Sickle Cell Disease Treatment OXBRYTA® (voxelotor) From Worldwide Markets. Pfizer. September 25, 2024. Accessed October 1, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-voluntarily-withdraws-all-lots-sickle-cell-disease.}
2. _{Center for Drug Evaluation and Research. FDA is alerting patients and health care professionals about the voluntary withdrawal of Oxbryta from the market due to safety concerns. U.S. Food and Drug Administration. September 26, 2024. Accessed October 1, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerting-patients-and-health-care-professionals-about-voluntary-withdrawal-oxbryta-market-due.}
3. _{EMA recommends suspension of Sickle Cell Disease Medicine Oxbryta. European Medicines Agency (EMA). September 26, 2024. Accessed October 1, 2024. https://www.ema.europa.eu/en/news/ema-recommends-suspension-sickle-cell-disease-medicine-oxbryta.}
4. _{Message from NASCC on Pfizer’s Decision to Withdraw Oxbryta (Voxeletor). NASCC. Accessed October 1, 2024. https://sicklecellcenters.org/message-from-nascc.}