A clinical study testing a Pliant Therapeutics drug once considered a promising prospect for treating a fatal lung disorder is now on pause at the recommendation of independent outside observers. Pliant disclosed few details and said it is still reviewing data, but the clock is ticking for the company to figure out next steps for the drug and the patients in the clinical trial.
The pause on the Phase 2b test is voluntary, Pliant said in its announcement after Friday’s market close. No new idiopathic pulmonary fibrosis (IPF) patients will be enrolled during this pause. Currently enrolled participants will remain in the study but will not be dosed with the experimental drug, bexotegrast. The study will remain blinded to preserve integrity of the data. Pliant said it has informed clinical trial investigators and is in the process of informing regulators.
IPF is a progressive disorder in which scar tissue builds up in the lungs, leading to worsening lung function that eventually becomes fatal. The few available treatments slow IPF’s progression but do not modify the course of the disease. Bexotegrast is a small molecule designed to inhibit TGF-beta, a signaling protein that leads to the production of collagen that impairs lung function.
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Phase 2a results reported last year showed that after 12 weeks, the Pliant drug led to a reduction in collagen while the placebo group showed an increase in collagen. Pliant also said the reduction in collagen correlated with improvement in lung function. No safety signals were reported in this study.
The trial that’s now paused is the Phase 2b portion of a Phase 2b/3 study designed to evaluate treatment with bexotegrast for 52 weeks. This placebo-controlled test was expected to post preliminary data in 2026. Over the course of a clinical trial, a data safety monitoring board, an independent body comprised of outside experts, evaluates safety and efficacy data at regular intervals. In Pliant’s announcement, the company said the board’s recommendation of a trial pause followed a prespecified data review.
To Leerink Partners analyst Faisal Khurshid, the voluntary pause and the continued blinding of the trial could mean the trial did not trigger pre-specified stopping criteria for safety or efficacy. But it also means the board saw something concerning enough to recommend pausing all patient dosing, he said in a note sent to investors.
Since the study did not meet pre-specified stopping criteria, Pliant may not be required to unblind the study, Khurshid said. Unblinding the study would mean all data integrity would be lost. Khurshid added that the board may be taking a conservative stance of not providing the exact reasoning to Pliant. That leaves the company to choose whether to unblind the data to learn the reason. Losing data integrity means Pliant would need to start over, assuming there is a path forward for the drug. The other choice is to maintain the blind and try to work with the board in a way that does not compromise data integrity.
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“In theory we think the resolution could be something like stopping one of the dose levels, excluding certain patient types, or prohibiting certain background therapies,” Khurshid said. “Again, this is all speculation. It will be important this occurs quickly as many patients were midway through a 52-week dosing period and the handling of the dosing suspension may become an issue the longer this goes.”
If the study is salvageable, moving forward would likely require a major amendment to the clinical trial protocol, Khurshid said. He added that even in an optimistic scenario, Pliant may need to restart a pivotal clinical trial program, which would mean a multi-year delay. Investors did not welcome any of these options. Shares of Pliant opened Monday at $3.02, down more than 61% from Friday’s closing price.
Pliant is one of several companies working to develop new drugs for IPF. Boehringer Ingelheim is at the front with nerandomilast, a small molecule designed to inhibit phosphodiesterase 4B (PDE4B), an enzyme whose roles include regulating inflammation. After announcing this drug met the main goal of its pivotal IPF studies last September, the company said it planned to seek approvals from the FDA and other regulators around the world.
Nerandomilast is also in development for a different respiratory condition, interstitial lung disease. On Monday, Boehringer reported the drug met the main goal of a Phase 3 study in this indication. Full safety and efficacy data will be released in the second quarter of this year.
Meanwhile, PureTech Health is developing deupirfenidone (formerly LYT-100), which employs chemical modifications to improve the tolerability of the old IPF drug pirfenidone. In December, PureTech reported its drug met key goals of a Phase 2b study with results showing improvement in measures of lung function. Another company, Insilico Medicine, is in mid-stage clinical development with ISM001-055, a small molecule inhibitor of an enzyme called TNIK. This IPF drug candidate was discovered with Insilico’s artificial intelligence platform technology.
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