Eric LeFebvre, MD, Chief Medical Officer at Pliant Therapeutics, discusses positive safety and efficacy data from the phase 2a INTEGRIS-IPF clinical trial of PLN-74809 in patients with idiopathic pulmonary fibrosis (IPF).

IPF is a chronic, progressive, fibrosing lung disease with few treatment options and a poor prognosis. Common symptoms of IPF include 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 the disease. 

As Dr. LeFebvre explains, INTEGRIS-IPF is a Phase 2a, randomized, dose-ranging, double-blind, placebo-controlled trial evaluating the safety, tolerability, and pharmacokinetics of PLN-74809 administered over 12 weeks in patients with IPF. Patients were enrolled in doses of 40 mg, 80 mg, 160 mg or 320 mg, with a 3:1 randomization ratio (active:placebo) and stratification based on use of standard of care therapy (nintedanib and pirfenidone). The primary endpoint is the evaluation of the safety and tolerability of PLN-74809. The secondary endpoint is the assessment of pharmacokinetics across a dose range. Exploratory endpoints will measure change in Forced Vital Capacity (FVC), HRCT-based Quantitative Lung Fibrosis (QLF) score and selected biomarkers.

The trial met its primary and secondary endpoints. PLN-74809 was well tolerated at all three doses tested. Of the 67 patients treated with PLN-74809, 65 (97%) completed 12 weeks of treatment with no discontinuations due to adverse events. No deaths or drug-related serious adverse events were reported. Most treatment emergent adverse events were mild or moderate in severity. PLN-74809 also exhibited dose-proportional increases in plasma concentrations, consistent with previous studies. The trial’s exploratory efficacy endpoints assessing changes in forced vital capacity (FVC) and Quantitative Lung Fibrosis (QLF) imaging demonstrated a dose-dependent treatment effect on FVC and QLF versus placebo over 12 weeks in PLN-74809 treated patients. 

A dose-dependent reduction in the proportion of patients with percent predicted FVC (FVCpp) decline of ≥10% was observed across treatment groups. 18.2%, 8.7% and 4.5% of patients experienced a ≥10% decline in FVCpp in the 40 mg, 80 mg and 160 mg treatment groups, respectively, compared to 17.4% in the placebo group. A decline of ≥10% in FVCpp at 12 weeks is associated with an increased risk of death in IPF patients over a two-year period.

An increase in QLF score is associated with an increase in pulmonary fibrosis. The mean percentage change in QLF at 12 weeks was 3.15%, 0.70% and 0.00% in the 40 mg, 80 mg and 160 mg treatment groups, respectively, compared to 1.15% in the placebo group. These findings suggest a dose-dependent antifibrotic effect of PLN-74809, consistent with its mechanism of action and preclinical findings.

Pliant Therapeutics has recently completed enrollment in the 320 mg cohort of the INTEGRIS-IPF Phase 2a trial. The 12 week interim data from the 320 mg cohort is anticipated in early 2023. The above data is intended to be shared with regulatory authorities soon to discuss the late-stage development of PLN-74809.

To learn more about IPF and other rare lung disease, visit checkrare.com/diseases/lung-diseases/