Pfizer has announced the voluntary withdrawal of its sickle cell disease (SCD) drug, Oxbryta® (voxelotor), following the European Medicines Agency's (EMA) disclosure of 16 deaths in clinical trials potentially linked to the medication. The decision encompasses all markets where Oxbryta has been approved and includes the cessation of all clinical trials and expanded access programs related to the drug.
The withdrawal was prompted by data from clinical studies indicating that Oxbryta's benefits no longer outweigh the risks to patients. Pfizer stated that the data suggested an imbalance in vaso-occlusive crises and fatal events, necessitating further assessment.
EMA Findings
The EMA disclosed findings from two Phase III trials where a total of 18 deaths occurred, with all but two linked to Oxbryta. In the Phase III GBT440-032 trial (HOPE Kids 2; NCT04218084), eight deaths occurred in patients dosed with Oxbryta compared to two in the placebo group. This trial was designed to assess the effects of voxelotor on cerebral arterial blood flow in children aged 2 to 15 with SCD at high risk of stroke, recruiting 236 patients across multiple countries.
In the second Phase III trial, GBT440-042 (RESOLVE; NCT05561140), eight deaths were reported in the open-label portion of the study. The EMA noted that the total number of deaths was higher than anticipated. This trial assessed the effects of voxelotor on leg ulcers in 88 patients aged 12 and older.
A third Phase III trial, GBT440-038 (NCT04188509), an open-label extension study evaluating the long-term safety and SCD-related complications of voxelotor, is also affected by the halt.
Context and Next Steps
The EMA has cautioned that there is currently no clear evidence that Oxbryta caused any of the deaths, and information about many cases is still being awaited. Some cases may be linked to infections, including malaria. Pfizer has notified regulatory authorities about its findings and is withdrawing Oxbryta from the market to further investigate the study data.
Pfizer acquired Oxbryta through its $5.4 billion acquisition of Global Blood Therapeutics (GBT) in October 2022. Oxbryta generated $338 million in worldwide sales last year, a significant increase from the $73 million reported by Pfizer for 2022 after the acquisition. In the first half of this year, sales reached $176 million, up 19% from the previous year.
The SCD treatment landscape has recently expanded with the FDA approval of Casgevy™ (exagamglogene autotemcel) and Lyfgenia™ (lovotibeglogene autotemcel) in December, offering new therapeutic options for patients.
