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Pliant Reports Positive Data from Phase 2a Trial of Bexotegrast in Patients with IPF

January 23, 2023

Pliant Therapeutics reported 12-week interim data from a phase 2a clinical trial of bexotegrast in patients with idiopathic pulmonary fibrosis that showed the study met its primary and secondary endpoints.

The results were in the 320 mg dose group of participants in the INTEGRIS-IPF and demonstrated that bexotegrast was well tolerated over a 12-week treatment period and displayed a favorable pharmacokinetic profile. The news sent shares of Pliant up more than 50 percent in early trading.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing lung disease of unknown cause with few treatment options and a poor prognosis. Patients experience debilitating symptoms, including shortness of breath and difficulty performing daily activities, such as walking and talking. Currently, there is no pharmacological cure for IPF, with neither of the approved two therapies demonstrating an ability to stop the progression of IPF. Therefore, there is a high unmet need for new therapeutic options to address the symptoms and modify the disease progression of this grievous illness.

Pliant’s lead product candidate, bexotegrast, is an oral small molecule dual selective inhibitor of αvß6 and αvß1 integrins that is in development in the lead indications for the treatment of IPF, and primary sclerosing cholangitis.

The trial’s exploratory efficacy endpoints assessed changes in forced vital capacity (FVC), Quantitative Lung Fibrosis (QLF) imaging and biomarkers. Bexotegrast at 320 mg demonstrated a statistically significant mean increase in FVC from baseline at all timepoints, surpassing all lower dose cohorts, and showed a strong treatment effect on FVC percent predicted (FVCpp), QLF, and profibrotic biomarkers versus placebo at 12 weeks.

The INTEGRIS-IPF phase 2a trial is evaluating bexotegrast at once-daily doses of 40 mg, 80 mg, 160 mg, 320 mg or placebo for 12 weeks in 119 patients with IPF.

The 320 mg group enrolled 21 patients in the active arm and eight patients in the placebo arm. Comparable to the lower dose groups, approximately 80 percent of all enrolled patients were on standard of care and were equally distributed between nintedanib and pirfenidone. The 320 mg group will continue until all patients have been treated for at least 24 weeks, with final data expected in the second quarter of 2023.

The exploratory efficacy endpoints of the INTEGRIS-IPF trial measured changes in FVC, high-resolution CT (HRCT)-based QLF, and profibrotic biomarkers over 12 weeks of treatment. A strong dose-dependent treatment effect was observed in the bexotegrast 320 mg dose group, with and without standard of care therapy. The bexotegrast 320 mg group demonstrated mean FVC increase of +29.5 mL relative to baseline at 12 weeks, versus a decline of 110.7 mL in the placebo group resulting in a 140 mL increase compared to placebo. Mean increases in FVC versus placebo reached statistical significance at all timepoints.

A decline of ≥10 percent in FVCpp at 12 weeks has been associated with increased mortality in IPF patients over a two-year period. Over 12 weeks of treatment, no patients in the 320 mg group experienced ≥10 percent decline in FVCpp. An increase in QLF score has been associated with worsening of pulmonary fibrosis. The mean percentage change in QLF at 12 weeks was 0.20 percent in the 320 mg group versus 1.46 percent in the placebo group.

PRO-C3, a serum biomarker of type III collagen synthesis, is elevated in patients with IPF and associated with progressive disease. The 320 mg group demonstrated a reduction in PRO-C3 at both 4 and 12 weeks versus placebo.

Elevated integrin beta-6 plasma levels have been associated with ILD progression as defined by mortality, transplant or ≥ 10 percent relative reduction in FVC (mL) over 12 months. The 320 mg group demonstrated a reduction in integrin beta-6 at both 4 and 12 weeks versus placebo.

The company said the findings support a potential dose-dependent antifibrotic effect of bexotegrast, consistent with its mechanism of action and preclinical findings.

“Data from the INTEGRIS-IPF trial have far exceeded our expectations, supporting bexotegrast’s favorable safety profile and demonstrating a statistically significant treatment response on FVC at 320 mg,” said Éric Lefebvre, chief medical officer at Pliant Therapeutics. “Additionally, we are extremely encouraged to see a consistent dose response on FVC, QLF and profibrotic biomarkers. We look forward to advancing bexotegrast into phase 2b clinical development.”

Photo: Éric Lefebvre, chief medical officer at Pliant Therapeutics

Author: Rare Daily Staff

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