Pliant Therapeutics has announced positive mid-stage clinical trial data for bexotegrast in patients living with primary sclerosing cholangitis (PSC) and suspected moderate-to-severe liver fibrosis.
The phase 2a clinical trial INTEGRIS-PSC has been evaluating the drug at once-daily oral doses for up to 12 and 48 weeks in 121 patients with PSC and suspected liver fibrosis.
Affecting more than 100,000 patients worldwide, PSC is a rare, progressive liver disease characterised by inflammation and fibrosis, with progressive liver and biliary damage leading to cirrhosis and liver failure.
The dose-ranging, placebo-controlled study randomised patients into different dose groups, including 40mg, 80mg and 160mg or placebo up to 12 weeks, and 320mg or placebo for up to 48 weeks.
Already granted fast track and orphan drug designations from the US Food and Drug Administration (FDA), as well as an orphan drug designation from the European Medicines Agency in PSC and idiopathic pulmonary fibrosis, bexotegrast is an oral, small molecule, dual-selective inhibitor of αvß6 and αvß1 integrins.
Patients from the 320mg cohort group met the primary endpoint of safety, demonstrating that bexotegrast was well tolerated up to 40 weeks of treatment.
From weeks 12 to 24, a stable Enhanced Liver Fibrosis (ELF) score was observed in the overall bexotegrast-treated population compared to placebo, and the drug improved markers and symptoms of cholestasis, including alkaline phosphatase, magnetic resonance imaging, self-reported itch and common PSC-associated adverse events, and showed decreased ALP levels compared to increased ALP on placebo.
In addition, results showed that 320mg bexotegrast demonstrated improvement in liver stiffness versus placebo at week 24, as well as a reduction in ELF score in patients at higher risk of disease progression compared to an increase in ELF on placebo.
Éric Lefebvre, chief medical officer, Pliant, commented: “These longer-term INTEGRIS-PSC data continue to highlight bexotegrast’s favourable safety and tolerability profile, further validating its broad antifibrotic activity in diseases of unmet need and suggests the potential for disease stabilisation.”
Following a meeting with the US regulator to review the potential development path of bexotegrast in PSC, the FDA is supportive of a 52-week dose-ranging phase 2b trial.
