Pliant Therapeutics has terminated its idiopathic pulmonary fibrosis (IPF) program after digging into the increased rate of adverse events from a 2b/3 trial of its lead candidate bexotegrast.
Back in March, the Californian biotech announced it was discontinuing the Beacon-IPF phase trial because of safety worries attached to the med. While Pliant said there was evidence of efficacy, the trial’s independent data safety monitoring board as well as an outside expert panel found an “imbalance in unadjudicated IPF-related adverse events between the treatment and placebo groups [which] led to the discontinuation of the trial.”
Since then, Pliant has taken a closer look at the trial data and found that both the 160-mg and 320-mg doses of bexotegrast—a dual inhibitor of the αvβ6 and αvβ1 integrins—showed an “unfavorable risk-benefit profile.” Specifically, patients who received the drug instead of placebo saw an increased risk of adverse events associated with IPF disease progression, which Pliant defined as “events of worsening of IPF and acute IPF exacerbation, respiratory-related hospitalization, and/or all-cause mortality.”
These issues may not have been picked up by a successful 12-week phase 2 trial of bexotegrast as the average time to disease progression in March’s failed trial was 33 weeks, Pliant noted.
When it came to the drug’s efficacy, the bexotegrast 160-mg and 320-mg treatment groups were tied to improvements in forced vital capacity decline of 72 mL and 46 mL, respectively, Pliant said in the June 27 release. By Week 24, these improvements had fallen to 58 mL and 8 mL.
“Although the decision to discontinue bexotegrast in IPF is disappointing for us and the many patients in need of new treatment options, we believe it is the right decision to protect patient safety,” Pliant’s CEO Bernard Coulie, M.D., Ph.D., said in the release. “We sincerely thank all patients, their caregivers, the study investigators and their research teams who were part of the BEACON-IPF clinical program for their extensive efforts.”
Last month, Pliant announced a head count reduction of 45% as part of a “strategic restructuring of its workforce.” The company said in Friday’s release that these layoffs align with the biotech’s updated strategy.
With bexotegrast thrown on the scrap heap, this strategy is now headed up by PLN-101095, an inhibitor of αvβ8 and αvβ1 integrins that is designed to block TGF-β activation in tumors. The asset is in a phase 1 trial both as a monotherapy and in combination with Merck & Co.’s PD-1 inhibitor Keytruda in patients with solid tumors resistant to immune checkpoint inhibitors.
The biotech has also secured the nod to begin a phase 1 trial of its muscular dystrophies candidate PLN-101325.