New phase 2 data of Pliant Therapeutics’ liver disease treatment shows that the highest dose was safe and effective at slowing progression relative to placebo, on par with lower dose data reported last fall.
However, the new figures indicate the 320 mg regimen of bexotegrast did not outperform the previous doses in a measure of liver progression.
The South San Francisco biotech said Monday that the 320 mg dose passed both the primary and secondary endpoints in a phase 2a trial of patients with primary sclerosing cholangitis and suspected fibrosis, proving that it was both well tolerated and that blood concentrations of the drug increased with dose. Sclerosing cholangitis is a condition where bile ducts are inflamed and scarred, limiting their function and causing bile build-up in the liver.
Pliant said that 96% of treated patients completed the 12-week regimen and that among them no drug-related serious or severe adverse events were reported. That matches similar safety data of the 40 mg, 80 mg and 160 mg doses previously disclosed in September 2023.
On the exploratory efficacy endpoint, which assessed the mean change in the enhanced liver fibrosis (ELF) test, the 320 mg dose stymied disease progression relative to placebo but patients still saw their fibrosis progress more than on any of the other three doses, particularly the 160 mg dose. The average change in ELF score was 0.22 for patients given 320 mg, compared to 0.9 for those who received 160 mg. The latter was statistically significant when compared to the progression of patients given placebo, the company noted when it announced those results.
The biotech also reported yesterday that the 320 mg dose reduced PRO-C3 levels—a biomarker for the formation of fibrotic tissue—relative to placebo. More granular data comparing PRO-C3 across dose levels and placebo was not included.
Investors appeared to be unimpressed by the data, sending the company’s shares down more than 20% shortly after the markets opened Monday morning, from $17.40 to $13.88.
Next up is a meeting with regulatory authorities to discuss next steps. Kris Kowdley, M.D, director of the Liver Institute Northwest and a professor of medicine at Washington State University, said in the release that the data “present a strong rationale” for studying the drug in a larger late-stage trial.
Pliant previously said in a third-quarter earnings report in November that 24-week data of the 320 mg group was expected by the middle of 2024.