Sickle cell disease (SCD) is an inherited blood disorder caused by a mutation in the hemoglobin gene (HbS). The abnormal hemoglobin causes red blood cells to become rigid and sickle-shaped, leading to chronic anemia, severe pain crises, and organ damage from blocked blood vessels.
While SCD is most common among people of African, Caribbean, Middle Eastern, and South Asian ancestry, its prevalence is rising in Europe, particularly in France and the United Kingdom, due to migration from regions where the disease is more common.
Prior to Oxbryta’s approval in 2022, treatment options for SCD were limited. The drug was authorized for patients aged 12 years and older to treat hemolytic anemia, offering new hope for reducing the frequency of blood transfusions and improving red blood cell function.
Safety Signals Triggered by Clinical Trial Deaths
Oxbryta was designed to inhibit hemoglobin S polymerization, increasing the oxygen affinity of red blood cells and improving their flexibility. However, recent trial data raised serious safety red flags.
The first halted study — a pediatric trial in London — showed an imbalance in mortality, with eight deaths reported in the voxelotor group versus two in the placebo group.
A second trial evaluating the drug’s effect on leg ulcers, a common SCD complication, also reported unexpected fatalities. Within 24 weeks, nine deaths occurred among patients receiving voxelotor, compared to none in the placebo arm.
Further analyses revealed that patients receiving the drug experienced more vaso-occlusive crises — sudden, severe pain episodes caused by blood flow blockage — compared to those on placebo.
EMA Maintains Suspension Pending Final Decision
In September 2024, the EMA issued a temporary suspension of Oxbryta’s marketing authorization and advised healthcare providers to transition patients to alternative therapies while an in-depth safety review was underway.
The Committee for Medicinal Products for Human Use (CHMP) has now confirmed that the suspension will remain in place. The committee found no clear mechanism explaining the increased deaths and no identifiable subgroup of patients who might safely benefit from continued treatment.
“Although the exact cause of the safety signals remains unclear, the inability to mitigate risk or identify safer use scenarios means the product cannot remain on the market,” the EMA said in its statement.
The CHMP’s recommendation will now be forwarded to the European Commission, which will issue a final, legally binding decision applicable across all EU member states.
Impact on Patients and Next Steps
The withdrawal of Oxbryta marks a setback in the treatment landscape for sickle cell disease, a condition with few disease-modifying therapies. Other available options include hydroxyurea, blood transfusions, and newer biologic agents such as crizanlizumab.
Pfizer and regulatory authorities are expected to continue evaluating the clinical data to better understand the observed risks and explore possible safety mitigations in future trials.
Source: European Medicines Agency – “Sickle Cell Drug Suspension Confirmed by EMA”