Pliant Therapeutics Reports Positive Long-Term Phase 2a INTEGRIS-PSC Trial Results for Bexotegrast

Pliant Therapeutics, Inc. recently released promising 24-week data from their Phase 2a clinical trial, INTEGRIS-PSC, examining the efficacy and safety of bexotegrast in patients with primary sclerosing cholangitis (PSC) and moderate to severe liver fibrosis. This randomized, double-blind, placebo-controlled trial assessed the impact of a 320 mg dose of bexotegrast, which demonstrated favorable outcomes in terms of safety and efficacy.

The primary objective of the trial was to evaluate the safety and tolerability of bexotegrast at a 320 mg dosage over a period extending up to 40 weeks. The results were positive, showing that the drug was well tolerated with no severe or serious adverse events related to the treatment. Common adverse events, such as pruritus and cholangitis, were less frequently observed in patients treated with bexotegrast compared to those receiving a placebo.

The trial also explored the efficacy of bexotegrast by measuring liver stiffness through transient elastography (TE) at 24 weeks, liver fibrosis markers including the Enhanced Liver Fibrosis (ELF) score, liver biochemistry, and magnetic resonance imaging (MRI). At 24 weeks, the 320 mg cohort showed a reduction in liver stiffness compared to the placebo group. This is significant as liver stiffness is indicative of liver fibrosis, a major concern in PSC patients. The ELF score, particularly in patients with a baseline ELF score greater than 9.8, also demonstrated improvement, suggesting a reduced risk of disease progression for those treated with bexotegrast.

Further supporting the drug’s efficacy, bexotegrast-treated patients exhibited a decrease in alkaline phosphatase (ALP) levels over 24 weeks, in contrast to the placebo group which saw an increase. ALP is a vital marker in assessing liver function and cholestasis. The MRI imaging revealed enhanced hepatocyte function and improved bile flow in patients receiving the 320 mg dose of bexotegrast from Week 12 to Week 24.

INTEGRIS-PSC was conducted across multiple countries and designed to evaluate various doses of bexotegrast, from 40 mg to 320 mg. The 320 mg cohort included 27 patients receiving the active drug and 9 on placebo. Dr. Éric Lefebvre, Chief Medical Officer of Pliant, highlighted that these results underscore bexotegrast’s safety and its potential in stabilizing the disease, further validating its broad antifibrotic properties.

Bexotegrast also reduced symptoms associated with cholestasis. Patients on the drug reported a stable itch score, unlike the placebo group which saw an increase. MRI sub-studies indicated further improvements in bile flow and liver function, with fewer adverse events related to pruritus and cholangitis in the treatment group.

Gideon Hirschfield, a principal investigator in the INTEGRIS-PSC trial, expressed optimism about these results, noting that they align well with previous data and demonstrate bexotegrast’s potential for treating fibrotic diseases. The study's findings have provided clarity on the next steps for the PSC development program, as guided by recent discussions with the FDA.

PSC is a rare and progressive liver disease characterized by inflammation and fibrosis, often leading to cirrhosis and liver failure. Affecting more than 30,000 patients in the U.S. and over 100,000 globally, there are currently no approved therapies for PSC by the FDA or EMA. Therefore, the development of effective treatments like bexotegrast is crucial for addressing this unmet medical need.

In summary, the INTEGRIS-PSC trial highlights bexotegrast's potential as a safe and effective treatment for PSC, showing improvements in liver stiffness, ELF scores, ALP levels, and overall liver function. These findings pave the way for further development of bexotegrast in treating PSC and other fibrotic diseases.