Pfizer withdraws Oxbryta from global markets, cites safety concerns
Benefits don’t outweigh risks, says company as it reviews data
Pfizer has voluntarily withdrawn Oxbryta (voxelotor), a conditionally approved oral therapy for sickle cell disease (SCD), from worldwide markets, saying clinical data shows the treatment’s benefit “no longer outweighs the risk.”
Citing an imbalance in vaso-occlusive crises (VOCs) and deaths occurring in patients given Oxbryta in postmarketing clinical studies, the company said it is also discontinuing all global clinical trials and expanded access programs.
“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, Pfizer’s chief medical officer and head of worldwide medical and safety, said in a company press release. “We advise patients to contact their physicians to discuss alternative treatment while we continue to investigate the findings from our review of the data.”
The move comes on the heels of findings disclosed by the European Medicines Agency (EMA) from two Phase 3 clinical trials of Oxbryta in which 16 deaths occurred in patients who had been treated with the medication.
Deaths during trials
In the HOPE Kids 2 trial (NCT04218084), eight participants treated with Oxbryta died, compared with two patients who had been given a placebo. The study’s main goal was to evaluate whether Oxbryta could improve blood flow in the brains of 236 children, ages 2-14, with SCD who are at risk of stroke.
The second Phase 3 trial, called RESOLVE (NCT05561140), assessed Oxbryta’s impact on leg ulcers in 88 SCD patients, ages 12 and older. Eight deaths occurred in the open-label portion of the study.
The Committee for Medicinal Products for Human Use, which had been reviewing data on Oxbryta following reports that some patients participating in studies had more VOCs during treatment than they did before starting the medication, recommended the suspension of Oxbryta’s marketing authorization as a precautionary measure while the review of emerging data is ongoing.
In the meantime, EMA advised doctors to not prescribe Oxbryta to new patients, and to contact patients currently on the medication to stop treatment and discuss possible alternatives.
The U.S. Food and Drug Administration (FDA) has alerted patients and healthcare professionals about Oxbryta’s voluntary withdrawal and the need to stop treatment. The U.S. agency has been conducting a safety review of Oxbryta’s post-marketing trial data, real-world registry studies, and post-marketing data from the FDA Adverse Event Reporting System (FAERS). The FDA said it will communicate any additional findings upon the conclusion of the safety review, if necessary.
“Our primary concern is for patients who suffer from SCD, which remains a very serious and difficult-to-treat disease with limited treatment options,” Habtezion said.
Initially developed by Global Blood Therapeutics, now a Pfizer subsidiary, Oxbryta received conditional approval from the FDA in 2019 for SCD patients, ages 12 and older. The approval was extended to children as young as 4 in 2021. In 2022, the therapy was approved in the European Union, when given alone or in combination with the standard SCD treatment hydroxyurea, for patients ages 12 and older.
The therapy is designed to stop the sickling and destruction of red blood cells that mark SCD by preventing the clumping of hemoglobin, the protein that normally carries oxygen in red blood cells and is defective in people with SCD. This clumping alters the shape of red blood cells, which can block small blood vessels and lead to painful VOCs.
About the Author
