Inhaled frespaciguat fails to meet primary endpoint in PH-COPD trial

Results from the phase 2a INSIGNIA PH-COPD trial indicate that inhaled frespaciguat, an investigational soluble guanylate cyclase stimulator, did not significantly improve the 6-minute walk distance (6MWD) at week 24 compared to a placebo.

Presented by Dr. Gabor Kovacs at the CHEST 2026 Annual Meeting, the study randomized 128 patients with pulmonary hypertension associated with chronic obstructive pulmonary disease (PH-COPD). While the 6MWD improved by 11 meters with frespaciguat versus 4 meters with the placebo, the 7-meter difference lacked statistical significance.

Despite missing the primary endpoint, the trial reported nominal improvements in 6MWD at earlier timepoints and in N-terminal pro-B-type natriuretic peptide levels. Additionally, an exploratory endpoint showed a reduced risk of clinical worsening, with a hazard ratio of 0.35. Dr. Kovacs noted that the drug appeared pulmonary selective and did not cause harm, suggesting a need to analyze more effective endpoints for future studies.