Randomised, placebo-controlled trial of oral hymecromone in adults with pulmonary hypertension

Abstract

Background Pulmonary hypertension (PH) is a progressive cardiopulmonary condition associated with increased morbidity and mortality. The extracellular matrix component hyaluronan (HA) is linked to vascular remodelling and interstitial fibrosis in PH. We hypothesised that inhibition of HA synthesis with hymecromone could serve as a reverse-remodelling therapy in PH. Methods We performed a proof-of-concept phase IIa randomised, double-blind, placebo-controlled study in adults with pulmonary arterial hypertension and PH associated with interstitial lung disease (PH-ILD). Patients were randomised to a 5:3 ratio and stratified by PH group to receive oral hymecromone or placebo two times per day over 24 weeks. The primary endpoint was change in pulmonary vascular resistance (PVR). Results We enrolled 16 patients with PH with a median age of 62.0 years. There were no treatment-related adverse events leading to hymecromone discontinuation. No statistically significant difference in PVR was observed at 24 weeks for the experimental group compared with the placebo group (mean difference 0.61 Wood unit, 95% CI −1.5 to 2.7). Five patients with PH-ILD treated with hymecromone demonstrated an unadjusted absolute mean increase in 6 min walk distance of 66 m (SD 69.6) from baseline to 24 weeks and improvements in quality-of-life measures. Conclusion Our exploratory analyses suggest that treatment with hymecromone could lead to improvements in clinically meaningful functional parameters in patients with PH-ILD. Further investigations in larger patient cohorts are warranted. Trial registration number ClinicalTrials.gov: [NCT05128929][1]. All data relevant to the study are included in the article or uploaded as supplementary information. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05128929&atom=%2Fthoraxjnl%2Fearly%2F2025%2F05%2F31%2Fthorax-2024-222725.atom