Pfizer's investigational drug inclacumab, a P-selectin inhibitor aimed at reducing vaso-occlusive crises in sickle cell disease, failed to meet its primary endpoint in a Phase 3 trial, marking a significant setback for the company's SCD pipeline.

Despite the lack of efficacy, inclacumab was generally well tolerated, with common side effects including anemia, joint pain, headache, malaria, and respiratory infections.

Pfizer has not announced specific next steps for inclacumab but stated it remains committed to developing treatments for sickle cell disease and is analyzing the trial data to guide future efforts.

The company's remaining late-stage SCD candidate is osivelotor, an HbS polymerization inhibitor in Phase 3 development, amid increasing competition from gene therapies from Vertex, CRISPR Therapeutics, and bluebird bio.

Inclacumab was originally developed by Roche, acquired by GBT, and then acquired by Pfizer in 2022, with the aim to prevent platelet aggregation and VOC onset, but it did not prove effective in this trial.

Pfizer's broader SCD portfolio has faced recent setbacks, including the withdrawal of Oxbryta in September 2024 due to unfavorable risk-benefit data, despite its initial projection to reach $3 billion in peak sales.

The Thrive-131 trial involved over 240 patients with a history of recurrent VOC episodes and was designed to demonstrate a substantial reduction in crises over 48 weeks, but it showed no meaningful difference between inclacumab and placebo.