Positive Phase 2a INTEGRIS-PSC Trial Results for Bexotegrast 320 mg in PSC Patients

Pliant Therapeutics, Inc. has reported positive interim results from a Phase 2a clinical trial of bexotegrast for primary sclerosing cholangitis (PSC), a rare and progressive liver disease. The 320 mg dosage of bexotegrast showed promising signs of safety and tolerability over a 12-week period, with no severe or serious adverse events attributed to the drug. The trial, known as INTEGRIS-PSC, included patients with suspected moderate to severe liver fibrosis and compared bexotegrast to a placebo.

The study's primary and secondary endpoints were met, indicating not only the drug's safety profile but also its increasing plasma concentrations with dosage. The exploratory endpoints revealed reductions in liver fibrosis markers, specifically the Enhanced Liver Fibrosis (ELF) score and PRO-C3 levels, as well as improvements in hepatocyte function and bile flow, as evidenced by contrast MRI imaging.

Bexotegrast-treated patients exhibited stabilization of alkaline phosphatase (ALP) levels, contrasting with an increase observed in the placebo group. The drug also showed an increase in relative enhancement on contrast MRI, suggesting improved hepatocyte function, and reduced time to arrival to the common bile duct, indicating better bile flow.

The 320 mg dose group of the INTEGRIS-PSC trial enrolled 27 patients, with an additional 9 new patients in the pooled placebo arm. The trial is the first of its kind to use an enrichment strategy to enroll patients with suspected moderate to severe liver fibrosis based on liver stiffness measures or historical liver biopsies. The final data for the 320 mg dose group is expected in mid-2024 after all patients have been treated for at least 24 weeks.

Pliant Therapeutics' Chief Medical Officer, Éric Lefebvre, M.D., highlighted the importance of the drug's favorable safety and tolerability profile, especially considering the need for chronic therapies in vulnerable patient populations. The therapeutic profile of bexotegrast is becoming clearer, with its effects seen across multiple endpoints, suggesting its potential to impact PSC where therapies are urgently needed.

The company plans to share the trial data with regulatory authorities to discuss the potential path to registration. PSC is a disease that affects over 30,000 patients in the United States and over 100,000 worldwide, with no FDA or EMA-approved therapies currently available. The INTEGRIS-PSC trial is a crucial step towards providing new therapeutic options for this grievous illness.

Pliant Therapeutics is a clinical-stage biopharmaceutical company focused on the discovery and development of novel therapeutics for fibrotic diseases. Bexotegrast, the company's lead product candidate, is also being developed for the treatment of idiopathic pulmonary fibrosis (IPF) and has received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) in both IPF and PSC.