Background

Overexpression of integrins ?_v?₆ and ?_v?₁ activates latent TGF-? in IPF. Bexotegrast (PLN-74809), an oral, once-daily, dual-selective inhibitor of ?_v?₆ and ?_v?₁, may provide a novel IPF treatment via localized TGF-? inhibition.

Aims and objectives

Report long-term safety and tolerability, and durability of effects on FVC and fibrotic markers for bexotegrast 320 mg.

Methods

Participants were randomized: bexotegrast 320 mg (n=21) or placebo (n=8) for at least 24 but less than 48 weeks. Primary endpoints: safety and tolerability. Exploratory endpoints: change in FVC and Quantitative Lung Fibrosis (QLF) score at Week 24.

Results

No drug-related serious treatment-emergent adverse effects (TEAEs) occurred: most were mild and unrelated to study drug. The most common TEAE was diarrhea (31.8% bexotegrast, 37.5% placebo), mainly observed in participants on background therapy. No discontinuations occurred due to TEAEs after Week 12. Through Week 40, serious AEs (SAEs) occurred in 9.1% (bexotegrast) and 12.5% (placebo): one fatal SAE (bexotegrast) was unrelated to study drug (acute respiratory failure, following a cardiac ablation).

FVC decline was reduced in bexotegrast-treated participants vs. placebo at Week 12, with 50% of participants on bexotegrast showing improvement at Week 24. 89% of bexotegrast participants with improvement in FVC at Week 12 maintained this at Week 24. At Week 24, 71% of bexotegrast participants had stable/improved disease by QLF vs. 33% on placebo.

Conclusions

Bexotegrast 320 mg showed favorable safety and tolerability up to 40 weeks, and physiologic and radiographic evidence of an antifibrotic effect up to Week 24. Phase 2b evaluation is planned for mid-2023.