Inhaled mosliciguat improves outcomes in PH-ILD phase 2 trial
A randomized phase 2 trial found the experimental inhaled drug mosliciguat yielded substantial, consistent benefits in patients with pulmonary hypertension linked to interstitial lung disease. The therapy aims to reactivate cGMP signaling within the lungs while limiting systemic vasodilation, targeting dysfunctional enzyme forms that accumulate under oxidative stress. It builds on earlier sGC stimulator research that led to riociguat.
Mosliciguat is an inhaled soluble guanylate cyclase activator under study for pulmonary hypertension tied to interstitial lung disease. Unlike older sGC stimulators such as riociguat, it is designed to act on dysfunctional, heme-free, nitric oxide-insensitive enzyme forms that build up during oxidative stress. Inhaled delivery aims to restore cGMP signaling in the lungs while avoiding broad systemic vasodilation.
The phase 2 PHocus trial randomized 135 adults with PH-ILD across 87 centers in 20 countries. At 16 weeks, it met its primary endpoint, showing a 56.3% placebo-adjusted drop in pulmonary vascular resistance. Exercise capacity also improved, with six-minute walk distance rising by 35.2 meters versus placebo at week 16 and 52.7 meters at week 24 in exploratory analysis.
If approved, this inhaled approach may offer a new option for people with PH-ILD, a rare and difficult condition, potentially improving breathing capacity and daily function. Clinicians and health systems could gain another targeted therapy, though access, cost, and long-term safety remain uncertain. Patients with underlying interstitial lung disease and pulmonary vascular involvement may benefit most, but phase 3 confirmation is needed before broader societal impact is clear.