A committee of clinical trial monitors has advised Pliant Therapeutics to stop giving its experimental fibrosis drug to patients in a Phase 2 trial, seeding doubt about the therapy’s future.
Pliant said in a short statement late Friday that, following a routine data check by the committee, the company has voluntarily stopped enrolling and dosing patients with its drug, bexotegrast, in a Phase 2b/3 trial in idiopathic pulmonary fibrosis.
Pliant didn’t say whether the trial was stopped due to safety concerns or its drug being ineffective — two reasons an independent data committee might call for a pause in dosing. The company is currently reviewing data “to understand the [committee’s] rationale,” it said, and will keep the study blinded “to preserve trial integrity.”
Current study volunteers will remain in the trial and be monitored while the review is underway. In the meantime, though, the company has informed investigators of the data board’s decision and is in the process of disclosing the news to global health regulators.
The announcement, and lack of specific details involved, took investors and Wall Street analysts by surprise. “This is a unique situation that we (and most investors we have spoken to) have never seen before,” wrote Leerink Partners analyst Faisal Khurshid, in a research note on Sunday.
Without those details, Khurshid, and other analysts following the company, were left to speculate what might have triggered the trial monitors’ decision. An independent data safety monitoring board periodically evaluates safety and efficacy data throughout a clinical trial. The committee also follows certain guidelines, one of which is to recommend a company immediately unblind and stop a trial because an experimental treatment is clearly unsafe or ineffective.
Notably, in Pliant’s case, Khurshid wrote, the dosing halt is voluntary and the study is still blinded. That could mean data reviewers “saw something that gave enough concern” to stop treating patients, but not enough to end the study altogether, he wrote.
“Our understanding is [Pliant] management does not know the exact findings,” he added, “which seems like an impasse” because Pliant would have to choose between unblinding the study and losing its progress, or trying to resolve the issue while keeping the trial intact.
“At best, this may be resolvable by determining the trigger and perhaps modifying dosing/population in conjunction with [Food and Drug Administration], albeit with some added risk and disruption,” wrote Brian Abrahams, of RBC Capital Markets. But “at worst, it may reflect an insurmountable imbalance in toxicity or mortality, spelling the end of the program.”
Abrahams speculated the latter, given safety concerns have been observed in testing of drugs with similar mechanisms as bexotegrast.
Company shares fell by more than 60% in pre-market trading on Monday. At about $3 apiece, they’re at their lowest levels since Pliant went public at $16 per share in 2020.
The setback leaves the status uncertain of a program that has been closely watched by analysts because of its potential in idiopathic pulmonary fibrosis, a rare lung condition that’s long bedeviled drugmakers.
Though two treatments are available in Roche’s Esbriet and Boehringer Ingelheim’s Ofev, neither are cures and several other prospects have failed in testing. That’s left room for companies like Pliant, whose drug impedes a protein involved in the formation of scar tissue, to come up with a better option.
Earlier study results had indicated bexotegrast appeared safe and might help improve lung function. The ongoing study, BEACON-IPF, is a larger and longer late-stage trial designed to recruit about 360 participants and test whether bexotegrast can slow or halt disease progression after a year of treatment.
Pliant had been expecting to complete enrollment this quarter and report results next year.
