Pliant Reports Positive Results from Phase 2a Trial of IPF Therapy
July 11, 2022
Pliant Therapeutics reported positive data from INTEGRIS-IPF, its phase 2a clinical trial of its experimental therapy PLN-74809 in patients with the rare and chronic lung condition idiopathic pulmonary fibrosis
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. There is a high unmet need for new therapeutic options to address the symptoms and modify the disease progression of this grievous illness.
PLN-74809 is an oral, small molecule, dual-selective inhibitor of αvβ6 and αvβ1 being developed for the treatment of idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC). While expressed at very low levels in normal tissues, αvβ6 and αvβ1 integrins are upregulated in the pulmonary tissues of IPF patients, and in the liver tissues of PSC patients. Both of these integrins serve as activators of TGF-ß, leading to increased collagen production and, ultimately, fibrosis in these tissues. By blocking the activation of TGF-ß by both αvβ6 and αvβ1, Pliant believes PLN-74809 may slow and potentially halt the progression of fibrosis in these patient populations.
INTEGRIS-IPF is a randomized, double-blind, placebo-controlled phase 2a multinational study evaluating PLN-74809 at once-daily doses of 40 mg, 80 mg, 160 mg, or placebo for 12 weeks in 90 patients with IPF. The trial enrolled 67 patients in the active arms and 23 patients in the placebo arm. Approximately 80 percent of enrolled patients were on standard of care and were equally distributed between nintedanib and pirfenidone. The primary endpoint of the INTEGRIS-IPF trial is the evaluation of the safety and tolerability of PLN-74809. The secondary endpoint is an assessment of its pharmacokinetics.
The trial met its primary and secondary endpoints demonstrating that PLN-74809 was well tolerated over a 12-week treatment period and displayed a favorable pharmacokinetic profile. 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.
PLN-74809 was well tolerated at all three doses tested. Of the 67 patients treated with PLN-74809, 65 (97 percent) completed 12 weeks of treatment with no discontinuations due to adverse events. No deaths or drug-related serious adverse events (SAE) were reported. Most treatment emergent adverse events (TEAEs) were mild or moderate in severity.
“Data from the INTEGRIS-IPF trial exceeded our expectations exhibiting a favorable safety and tolerability profile and a treatment effect on FVC, the current registrational endpoint in IPF. Importantly, the treatment effect was also observed on top of standard of care therapy,” said Éric Lefebvre, chief medical offer at Pliant Therapeutics. “Additionally, the dose-dependent reduction observed in the proportion of patients experiencing a decline in percent predicted FVC of ≥10 percent underscores the potential of this novel investigational therapy to advance the treatment of IPF.”
Author: Rare Daily Staff
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