Pfizer Withdraws Voxelotor From Approved Markets, Will Discontinue Trials
The discontinuation comes after a review of the medication by the European Medicines Agency which found that “the total number of deaths was higher than anticipated.”
Pfizer has voluntarily withdrawn voxelotor (Oxbryta) from all approved markets and will discontinue all active clinical trials and expanded access programs worldwide for the drug. The decision on voxelotor, approved for the treatment of sickle cell disease (SCD), was based on clinical data that indicated the overall benefit of the drug no longer outweighs the risk for the patient population, including more deaths than expected, many of which were malaria-related.1
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“The safety and well-being of patients is of the utmost importance to Pfizer, and we believe this action is in the best interest of patients,” Aida Habtezion, MD, MSc, FRCPC, AGAF, chief medical officer and head of worldwide medical and safety at Pfizer, said in a news release. “Our primary concern is for patients who suffer from SCD, which remains a very serious and difficult-to-treat disease with limited treatment options. We advise patients to contact their physicians to discuss alternative treatment while we continue to investigate the findings from our review of the data.”1
The data show an imbalance in vaso-occulusive crises and fatal events requiring further assessment, according to the release. Pfizer notified regulatory authorities about the findings and the decision to withdraw the drug from the market as well as discontinuing distribution and clinical studies. The company will further review the available data and findings.1
The European Medicines Agency has started a review for the medication, citing a higher number of deaths with voxelotor compared with the placebo, with other trial data showing a total number of deaths that were higher than expected. In May 2024, the trials GBT 440-032 and GBT 440-042 were paused due to safety concerns, with the dosing paused for the open label extension trial, GBT 440-038. Eight deaths were reported in the treatment arm of GBT 440-032 compared with 2 in the placebo arm. For the voxelotor group, 3 individuals developed fatal malaria and 2 developed sepsis.2
Furthermore, there were an additional 9 deaths occurred in GBT 440-042, with 8 of the 9 occurring in the open label portion of the study. In at least 4 cases, malaria was also the cause or contributing factor. The European Commission requests an opinion from the Agency and CHMP by March 2024 to determine if the marketing authorization for the product should be maintained, varied, suspended, or revoked, according to the notification referral under Article 200 of Regulation (EC) 726/2004.2
Voxelotor is a hemoglobin S polymerization inhibitor approved in 2019 for adults and pediatric patients 12 years and older with SCD. The approval was based on data from the phase 3 HOPE study, including 274 individuals, which demonstrated statistically significant improvements in hemoglobin levels and reductions in red blood cell destructions.3
The rates of adverse events were similar between groups, with the most common occurring in 10% or more of patients. The AEs included headache, diarrhea, abdominal pain, nausea, fatigue, rash, and pyrexia. A grade 3 or higher AE occurred in 26% of those in the 1500 mg group, 23% of the 900 mg group, and 26% in the placebo group.3,4
The drug was also granted priority review in September 2019, which enabled it to become the first approved therapy that targeted hemoglobin polymerization, a primary driver of SCD.4
