Voxelotor, an oral drug used to treat sickle cell disease in adults and children over the age of 4, was withdrawn from the market worldwide in September 2024 and is no longer approved for use by the U.S. Food and Drug Administration. Withdrawal was based on additional data available to the manufacturer, Pfizer, which showed that the drug had more risks than benefits. However, no safety or efficacy data were provided at the time of withdrawal, and real-world studies independent of the manufacturer remain lacking.
In this study, the researchers evaluated real-world efficacy and safety of voxelotor before its withdrawal by examining the electronic health record data of 10,412 patients with sickle cell disease, 388 of whom had a voxelotor prescription. 97% of patients on voxelotor had the more severe form of sickle cell disease, HbSS. Compared to patients using other sickle cell drugs, those on voxelotor were older, predominantly female, and had lower levels of hemoglobin (a protein in the blood that transports oxygen through the body) and higher levels of reticulocytes (immature red blood cells that are increased in individuals with sickle cell disease, indicative of red cell breakdown).
Longitudinal analysis of this data showed that individuals on voxelotor did not experience a significant decrease in their number of vaso-occlusive (or pain) crises, had a small increase in hemoglobin levels (7.36±0.06 to 7.51±0.06 g/dL), and a small decrease in reticulocyte counts (10.2±0.3% to 9.6±0.3%). Eight patients (2.1%) taking voxelotor died, compared to 125 patients (3.8%) who died while using another disease-modifying therapy.
Overall, the researchers say it remains unclear if the small laboratory improvements patients on voxelotor experienced outweigh the drug’s potential reduction in oxygen delivery. It is also unclear if the US data are applicable to worldwide populations of patients with SCD, but additional studies independent of industry could help elucidate the risk-benefit profile.
