In patients with idiopathic pulmonary fibrosis (IPF), bexotegrast—an oral small molecule dual selective inhibitor of αvß6 and αvß1 integrins—was well tolerated and displayed a favorable pharmacokinetic profile, according to interim results from the multinational, randomized, double-blind, placebo-controlled, phase 2a INTEGRIS-IPF clinical trial.
Interim 12-week data from the bexotegrast 320-mg dose group demonstrated that the primary study endpoint—evaluation of the safety and tolerability of the agent—and the secondary study endpoint—assessment of the pharmacokinetics of the agent—were met.
No severe or serious drug-related adverse events (AEs) were reported over 12 weeks of treatment. All drug-associated AEs were mild or moderate in severity. Additionally, treatment with bexotegrast exhibited dose-proportional increases in plasma concentrations.
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The exploratory efficacy endpoints evaluated changes in forced vital capacity (FVC), high-resolution computed tomography (HRCT)-based quantitative lung fibrosis (QLF) imaging, and profibrotic biomarkers over 12 weeks of treatment.
Learn more about experimental therapies for idiopathic pulmonary fibrosis
The INTEGRIS-IPF trial is designed to assess bexotegrast administered at once-daily doses of 40 mg, 80 mg, 160 mg, 320 mg, compared with placebo, for 12 weeks in 119 patients with IPF. The 320-mg treatment group had 21 patients in the active arm and 8 individuals in the placebo arm. Approximately 80% of all enrolled participants were receiving standard of care, which was equally distributed between pirfenidone and nintedanib.
Results showed that the bexotegrast 320-mg treatment group experienced a mean FVC increase of 29.5 mL relative to baseline at 12 weeks, vs a decrease of 110.7 mL in the placebo group, equating to a 140-mL increase compared with placebo. In fact, mean increases in FVC vs placebo reached statistical significance at all time points evaluated.
Further, study results support a potential dose-dependent antifibrotic effect of bexotegrast, which is consistent with its mechanism of action and preclinical findings.
Evaluation of the bexotegrast 320-mg group will continue until all patients have received treatment for at least 24 weeks. It is anticipated that final data will be available in the second quarter of 2023.
According to Éric Lefebvre, MD, chief medical officer at Pliant Therapeutics, the biopharmaceutical company that markets bexotegrast, “Data from the INTEGRIS-IPF trial have far exceeded our expectations. . . . Additionally, we are extremely encouraged to see a consistent dose response on FVC, QLF and profibrotic biomarkers.”
“The statistically significant increase in mean FVC versus placebo seen throughout the 12-week treatment period of the INTEGRIS-IPF trial at 320 mg is unprecedented in clinical trials observed to date,” noted INTEGRIS-IPF principal investigator Lisa M. Lancaster, MD, professor of medicine at Vanderbilt University School of Medicine, Nashville, Tennessee. “Additionally, the dose-dependent changes in the beta-integrin biomarker data aligned with changes in FVC and the antifibrotic mechanism of action of bexotegrast.”
Reference
Pliant Therapeutics announces positive data from the INTEGRIS-IPF phase 2a trial demonstrating bexotegrast 320 mg was well tolerated and achieved statistically significant FVC increase in patients with idiopathic pulmonary fibrosis. News release. Pliant Therapeutics; January 22, 2023.
