Pliant Therapeutics halted its Phase 2b BEACON-IPF trial of bexotegrast for idiopathic pulmonary fibrosis (IPF) due to an imbalance in unadjudicated IPF-related adverse events between the treatment and placebo arms. However, the trial also revealed promising efficacy data regarding forced vital capacity (FVC). This marks the first late-stage IPF trial discontinued for safety concerns while simultaneously demonstrating potential treatment efficacy.
The discontinuation of a promising IPF trial based on safety concerns, despite positive efficacy signals, significantly impacts the IPF drug development landscape. It underscores the challenge of balancing efficacy and safety in this complex disease and may influence the design and evaluation criteria of future IPF clinical trials. The observed efficacy, despite the safety issues, suggests a potential therapeutic window for bexotegrast that warrants further investigation. This could lead to modified trial designs exploring lower doses or stricter patient selection criteria.
The BEACON-IPF trial involved two bexotegrast dose groups (160mg and 320mg) with a mean exposure duration of approximately 17 weeks. Although the overall percentage of IPF-related adverse events was similar across both dose groups (around 10%), the placebo group experienced a surprisingly low rate (below 3%). This discrepancy, not observed in the earlier Phase 2a INTEGRIS-IPF trial, triggered the trial’s discontinuation. Pliant plans to thoroughly analyze the complete BEACON-IPF data to better understand the drug’s benefit-risk profile and identify a potential therapeutic window. The company is considering future dose-ranging Phase 2b studies with lower bexotegrast doses in pulmonary fibrosis and potentially other non-respiratory indications, including liver diseases. Development of other clinical and pipeline assets, such as PLN-101095 for oncology, is continuing.
The BEACON-IPF trial results present a mixed outlook for bexotegrast. While the safety concerns necessitate a cautious approach, the observed efficacy signals warrant further exploration. A comprehensive data analysis will be crucial to determine the future development path for bexotegrast. This could involve exploring lower doses, different patient populations, or alternative indications where the benefit-risk profile may be more favorable. The outcome of this analysis will significantly influence the future of bexotegrast and potentially contribute to the understanding and treatment of fibrotic diseases.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
