Pliant Therapeutics Discontinues IPF Program Due to Safety Concerns

Pliant Therapeutics has announced the termination of its idiopathic pulmonary fibrosis (IPF) program following an in-depth analysis of adverse events in a phase 2b/3 trial of its lead candidate, bexotegrast. The decision marks a significant setback for the California-based biotech company and highlights the challenges in developing treatments for this severe lung disease.

Safety Concerns Outweigh Potential Benefits

The company's decision to discontinue the BEACON-IPF trial came after both an independent data safety monitoring board and an external expert panel identified an imbalance in unadjudicated IPF-related adverse events between the treatment and placebo groups. Further investigation revealed that patients receiving bexotegrast at doses of 160 mg and 320 mg experienced an increased risk of adverse events associated with IPF disease progression.

These events were defined as worsening of IPF, acute IPF exacerbation, respiratory-related hospitalization, and/or all-cause mortality. Notably, the average time to disease progression was 33 weeks, which may explain why these issues were not detected in the earlier successful 12-week phase 2 trial.

Efficacy Data and Trial Outcomes

Despite the safety concerns, bexotegrast showed some signs of efficacy. The 160 mg and 320 mg treatment groups demonstrated improvements in forced vital capacity (FVC) decline of 72 mL and 46 mL, respectively. However, by week 24, these improvements had diminished to 58 mL and 8 mL.

Bernard Coulie, M.D., Ph.D., CEO of Pliant Therapeutics, expressed disappointment but emphasized the necessity of prioritizing patient safety: "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."

Strategic Restructuring and Future Focus

In response to the setback, Pliant Therapeutics has implemented a strategic restructuring, including a 45% reduction in its workforce. The company is now redirecting its efforts towards other promising candidates in its pipeline.

PLN-101095, an inhibitor of αvβ8 and αvβ1 integrins designed to block TGF-β activation in tumors, has become the new lead asset. It is currently in a phase 1 trial, both as a monotherapy and in combination with Merck & Co.'s PD-1 inhibitor Keytruda, for patients with solid tumors resistant to immune checkpoint inhibitors.

Additionally, Pliant has received approval to initiate a phase 1 trial for PLN-101325, a candidate targeting muscular dystrophies. These developments signal the company's strategic pivot towards oncology and rare diseases as it seeks to recover from the setback in its IPF program.