Pfizer’s investigational therapy for sickle cell disease (SCD), inclacumab, has failed to meet its primary endpoint in a late-stage clinical trial, adding another challenge to the company’s $5.4 billion acquisition of Global Blood Therapeutics (GBT). The phase 3 study, known as Thrive-131, was designed to evaluate the drug’s ability to reduce painful vaso-occlusive crises (VOCs) in patients with SCD but did not show a significant benefit compared to placebo.
Inclacumab, a P-selectin inhibitor, was first developed by Roche before being acquired by GBT, which later became part of Pfizer in 2022. The therapy has been a central part of Pfizer’s efforts to expand its SCD pipeline following the purchase. Pfizer launched the Thrive program to test inclacumab in two phase 3 trials, with one halted in March 2024 due to slow recruitment. At that time, Pfizer said the discontinuation would not affect its target for regulatory approval in 2026.
The results disclosed on Friday mark a setback for the second trial. Thrive-131 enrolled more than 240 patients with a history of two to 10 VOC episodes in the previous year. Conducted as a randomized, double-blind, placebo-controlled study over 48 weeks, the trial was intended to demonstrate a statistically significant reduction in VOCs with inclacumab. Pfizer reported that the trial did not achieve this endpoint.
Despite the lack of efficacy, the company noted that the therapy was generally well tolerated. The most common treatment-emergent adverse events included anemia, arthralgia, back pain, headache, malaria, sickle cell anemia with crisis, and upper respiratory tract infection.
In response to the outcome, Michael Vincent, M.D., Ph.D., Pfizer’s chief inflammation and immunology officer, acknowledged the disappointment. “We recognize this news is disappointing for the sickle cell community, and we share their disappointment,” he said in the August 15 announcement. Vincent added that Pfizer would continue analyzing the data and share its findings with the broader medical and scientific community in an effort to further understanding of SCD.
Inclacumab was designed to block the P-selectin protein, which plays a role in the aggregation of platelets and the onset of VOCs. While the therapy aimed to reduce the frequency of these episodes, the latest trial showed no meaningful difference in VOC rates between the treatment and placebo arms across the 48-week study period.
The trial results follow earlier challenges for Pfizer’s SCD portfolio. In September 2024, the company withdrew Oxbryta, the key product from the GBT acquisition, after clinical data suggested that the risks outweighed the benefits of treatment. Oxbryta had once been projected to generate peak annual sales of $3 billion.
With Oxbryta no longer available and inclacumab’s future uncertain, Pfizer’s remaining late-stage SCD program is osivelotor, an HbS polymerization inhibitor now in phase 3 development. Meanwhile, the sickle cell treatment landscape has seen recent advances from gene therapies, including Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy, as well as bluebird bio’s Lyfgenia.
Pfizer has not announced next steps for inclacumab following the Thrive-131 results, but emphasized that it remains “focused on our mission of bringing much-needed treatments to patients with sickle cell disease.”
