Recently, Pfizer announced that its investigational key drug for sickle cell disease (SCD), inclacumab, failed to meet the primary endpoint in the Phase III THRIVE-131 study. This setback casts a shadow over Pfizer's strategic plans in this therapeutic area.
The Phase III THRIVE-131 study was designed to evaluate the efficacy of inclacumab in reducing the incidence of vaso-occlusive crises (VOCs). The results showed no statistically significant difference in VOC rates between the inclacumab group and the placebo group, indicating that the drug did not achieve its intended clinical benefit.
Sickle cell disease (SCD) is a hereditary blood disorder caused by an abnormality in hemoglobin molecules, which leads to the deformation of red blood cells into a sickle shape. This impairs blood flow and oxygen delivery, often resulting in symptoms such as severe pain and anemia. Patients frequently face sudden health crises, which impose a heavy physical, emotional, and financial burden on both individuals and their families.
Looking back at Pfizer's efforts in SCD treatment, in August 2022, the company acquired Global Blood Therapeutics (GBT) for a total transaction value of $5.4 billion, primarily to gain access to GBT's portfolio of three sickle cell disease drugs-including inclacumab.
Unfortunately, the other two drugs in the portfolio, Oxbryta and Osevelotor, have also fallen short of expectations.
Oxbryta (voxelotor) is a hemoglobin S allosteric modulator that was approved by the FDA in 2019 for the treatment of SCD, marking a significant breakthrough in the field at the time. However, in September 2024, Pfizer announced the global withdrawal of Oxbryta. This decision followed clinical and regulatory data revealing that patients taking Oxbryta had a mortality rate three times higher than those on placebo, leading to concerns over its risk-benefit profile and ultimately resulting in its discontinuation.
Osevelotor (GBT60110), the next-generation hemoglobin S polymerization inhibitor (also acquired through the GBT deal), initially showed promise in early studies. However, in December 2024, the FDA raised safety concerns, leading to a partial clinical hold on its Phase III trial. By May 2025, it was confirmed that the Phase III study had been fully suspended.
These setbacks highlight the complexity and challenges of developing effective treatments for sickle cell disease.
Despite the disappointments with inclacumab and other investigational drugs, global research efforts in SCD therapeutics continue. Scientists and pharmaceutical companies remain committed to advancing new treatments, offering hope for improved outcomes and a better quality of life for patients with this debilitating condition.
