Pfizer Halts Sickle Cell Trial Over Recruitment Issues

Pfizer recently decided to halt one of its two Phase III clinical trials assessing the efficacy of inclacumab, an anti-P-selectin antibody, in the treatment of sickle cell disease (SCD). This decision, which was recorded on ClinicalTrials.gov, was attributed to difficulties in patient recruitment since only 78 out of the planned 280 participants were enrolled. The trial, which began in December 2021, faced consistent challenges in attracting eligible candidates.

A Pfizer representative confirmed that the termination of the study was due to slow recruitment but emphasized that the company remains committed to achieving regulatory approval for inclacumab by 2026. Inclacumab, originally developed by Global Blood Therapeutics (GBT), is a human monoclonal antibody targeting the P-selectin protein. This protein plays a crucial role in cell adhesion processes and has been validated as a target to reduce the pain from vaso-occlusive crises (VOC) in SCD patients.

The drug received the FDA’s Orphan Drug and Rare Pediatric Disease designations in June 2022, highlighting its potential and its convenient quarterly dosing schedule compared to monthly infusions. In August 2022, Pfizer acquired GBT for $5.4 billion, gaining access to its SCD treatments, including Oxbryta (voxelotor), an FDA-approved oral treatment for patients four years and older. Inclacumab was part of this acquisition as well.

Post-acquisition, Pfizer took charge of the Phase III THRIVE program, which consists of two studies intended to test inclacumab’s effectiveness in reducing VOCs in SCD patients. While one of these studies has been terminated, the other continues and has successfully completed recruitment with 240 participants. Results from this active trial are expected to be available later in the year.

The study’s termination follows several significant developments in SCD treatment approvals. In December 2023, the FDA approved two landmark gene therapies: CRISPR-based Casgevy (exagamglogene autotemcel) from CRISPR Therapeutics and Vertex Pharmaceuticals, and lentiviral delivery-based Lyfgenia (lovotibeglogene autotemcel) from bluebird bio. Both therapies involve modifying the patient’s blood stem cells and reintroducing them as a single-dose infusion. Casgevy is priced at $2.2 million per patient, while Lyfgenia costs $3.1 million.

In January 2024, the Centers for Medicare and Medicaid Services revealed plans to create outcomes-based agreements with developers of these SCD gene therapies to manage rising healthcare costs effectively.