Results of a phase 2 study of GLPG1205 for idiopathic pulmonary fibrosis (PINTA)

Introduction: G-protein-coupled receptor 84 (GPR84), which is activated by a range of medium chain fatty acids, is involved in fibrotic processes. GLPG1205, a selective GPR84 antagonist, inhibits monocyte and neutrophil migration and activation among other actions. Aim: To assess the efficacy and safety of GLPG1205 vs placebo (PBO) in idiopathic pulmonary fibrosis (IPF). Methods: PINTA (NCT03725852) was a phase 2, randomised, double-blind, PBO-controlled, proof-of-concept trial in Europe and Oman. IPF patients received oral GLPG1205 100mg or PBO once daily, on top of standard of care (nintedanib/pirfenidone/neither) for 26 weeks. Primary endpoint: change from baseline (CFB) in FVC; other endpoints: safety, tolerability and functional respiratory imaging (FRI). PINTA was not powered for statistical significance. Results: 68 patients were dosed. Least squares (LS) mean (SE) CFB in FVC at Week 26 was −34mL (39) with GLPG1205 vs −76mL (47) with PBO (LS mean difference=42mL [95% CI −82, 166; p=0.495]). Total lung volume by FRI declined less with GLPG1205 compared with PBO. The most frequent adverse events (AEs) for GLPG1205 alone were GI disorders, particularly nausea (6/17 patients vs 0/8 on PBO). No relevant safety signals were seen for GLPG1205 alone or with pirfenidone. For GLPG1205 with nintedanib, higher rates of early discontinuations, high-grade treatment-emergent AEs, serious AEs and GI AEs were observed and there was 1 death (IPF exacerbation, unrelated to study drug). Conclusion: GLPG1205 resulted in smaller declines in FVC and total lung volume at Week 26 vs PBO, consistent with a therapeutic effect. This along with the observed safety profile for GLPG1205 alone supports further development. Funding: Galapagos