Pfizer announced disappointing results from its Phase III THRIVE-131 study evaluating inclacumab, an investigational P-selectin inhibitor for sickle cell disease (SCD), marking another significant setback in the company's efforts to address this debilitating condition. The monoclonal antibody failed to achieve its primary endpoint of significantly reducing vaso-occlusive crises (VOCs) in patients with SCD.
Study Design and Results
The THRIVE-131 trial was conducted as a randomized, double-blind, placebo-controlled study over 48 weeks, enrolling 241 participants aged 16 years and older with SCD. Patients selected for the study had experienced between two to ten VOCs within the previous year. Participants were randomly assigned to receive either inclacumab or placebo every 12 weeks throughout the study duration.
The trial's primary endpoint measured the rate of VOCs in patients receiving inclacumab compared to those receiving placebo. However, results showed no significant difference in VOC rates between participants receiving the investigational treatment and those receiving placebo.
Company Response and Commitment
Michael Vincent, M.D., Ph.D., chief inflammation & immunology officer at Pfizer, acknowledged the disappointing outcome. "We recognize this news is disappointing for the sickle cell community, and we share their disappointment," Vincent stated. "While the THRIVE-131 results did not meet our expectations, we remain committed to better understanding these results and sharing them with the medical and sickle cell community in the interest of advancing our collective understanding of sickle cell disease."
Vincent emphasized Pfizer's continued dedication to the therapeutic area, adding, "We remain focused on our mission of bringing much-needed treatments to patients with sickle cell disease. We are deeply grateful to the participants and investigators for their contributions to this important work. Their efforts are invaluable in informing future sickle cell research."
Impact on Global Blood Therapeutics Acquisition
The inclacumab failure represents the second major disappointment from Pfizer's $5.4 billion acquisition of Global Blood Therapeutics in 2022. The acquisition was headlined by Oxbryta, which was subsequently withdrawn from the market in September 2024, significantly impacting the deal's outlook.
BMO Capital Markets analyst Evan Seigerman commented on the cumulative impact of these setbacks, noting, "Pfizer's acquisition of Global Blood has proven disappointing with inclacumab's failure coming after Oxbryta's 2024 withdrawal from all approved markets."
Future Directions
Despite these challenges, Pfizer has stated its continued commitment to developing treatments for sickle cell disease. The company indicated it will pursue next steps in expanding its SCD treatment portfolio, including continued work with Oxbryta and osivelotor, as it seeks to address the significant unmet medical needs of patients living with this chronic condition.
