A once-daily inhaled drug could shake up pulmonary hypertension treatment

Mosliciguat, a potential first-in-class inhaled therapy, delivered impressive results in the PHocus phase 2 trial for adults with pulmonary hypertension associated with interstitial lung disease (PH-ILD) — one of the most difficult-to-treat forms of the condition. Presented at the European Respiratory Society 2026 International Congress, the findings are now fueling a phase 3 trial (PHrontier), which is open and enrolling.

Unlike existing sGC stimulators, mosliciguat works as an sGC activator, binding directly to the enzyme independent of nitric oxide. This allows it to deliver targeted pulmonary vasodilation while minimizing systemic side effects — a key concern in this fragile patient population. Currently, inhaled treprostinil (taken four times daily) is the only approved therapy for PH-ILD, making a well-tolerated once-daily alternative a significant potential advance.

By the Numbers

• -51.3% vs +6.6%: Reduction in pulmonary vascular resistance (mosliciguat vs placebo) at 16 weeks
• +20.3 m vs -14.9 m: Improvement in 6-minute walk distance
• -53.2%: Placebo-adjusted reduction in NT-proBNP (a cardiac strain biomarker)
• 12.1% vs 18.2%: Cough rate (mosliciguat vs placebo) — notably lower than placebo for an inhaled drug
• 135 patients enrolled; benefits persisted and grew through week 24

Why it matters: PH-ILD patients have long had limited therapeutic options. If phase 3 confirms these results, mosliciguat could become the first non-treprostinil approved option for this population — and potentially be used alongside treprostinil as a dual inhaled regimen.