Pliant posts high-dose data of oral IPF drug with ‘quite favorable’ safety, outlines trial plans

Pliant Therapeutics reported Monday morning that patients who got the high dose of its oral drug for idiopathic pulmonary fibrosis, or IPF, saw their disease stabilize. Importantly, Pliant noted its drug came with few treatment-related adverse events in a field where approved options have substantial side effects.

The early data sent Pliant’s stock $PLRX up 50%, from around $22 to nearly $35 a share.

IPF is a disease in which the lungs get scarred, making breathing difficult. Pliant’s drug, dubbed bexotegrast, blocks two integrins that upregulate TGF-β, an important cytokine which is not highly expressed in normal tissue but is in the lungs of IPF patients.

In Pliant’s trial, no patients in the high-dose arm of 320 mg saw their measurements in a forced breathing test decline more than 10%, the cutoff for disease progression. In July, Pliant reported data on the three lower doses of its drug, and patients who got the middle two doses (80 and 160 mg) had improved lung function compared to placebo.

Importantly here, the improvement on the breathing test was dose-dependent, meaning that the proportion of patients who saw disease progression decreased the higher the dose. In addition, when looking at biomarker data, patients who got the highest dose of the drug saw the greatest improvement.

One patient in the high-dose arm died during the trial after receiving cardiac ablation, and trial investigators said the death was unrelated to the treatment.

Greg Cosgrove

Currently, there are two approved drugs for IPF — Boehringer Ingelheim’s Ofev and Roche’s Esbriet. Both come with a number of side effects. In Pliant’s trial, the most common treatment-related adverse event was diarrhea, which impacted 17% of patients in the treatment arm compared to around 10% on placebo in the high-dose regimen.

Most patients in Pliant’s trial were also on standard of care, and Pliant VP of clinical development Greg Cosgrove suggested in an interview with Endpoints News that the adverse effects may have been related to the combination therapy.

“There remains tremendous unmet need because of tolerability issues, which lead to higher rates of discontinuation and those therapies decrease the rate of progression, but patients are still progressing and dying on treatment. So obviously, the safety profile of bexotegrast is quite favorable, and if the extension of the data continue to suggest stabilization, it really fills a tremendous unmet need,” Cosgrove said.

Moving forward, Pliant plans to release the 24-week data of the high-dose arm in the second quarter of the year and then plans to start a Phase IIb trial toward the middle of the year. CMO Éric Lefebvre said that he couldn’t comment on how many patients Pliant plans to enroll, but noted that it would look at patients on two doses, 320 mg and 160 mg, with endpoints out to one year.

Lefebvre also noted that 30% of patients would not be on standard of care. In addition, he said the trial could act as one of two registrational trials for FDA review, as opposed to two Phase III trials.

Others are in late-stage testing for IPF candidates. FibroGen has two Phase III trials, with one set to topline in the coming months. Roche also has a Phase III trial set to complete by the end of the year.

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