A phase 2 clinical trial of the investigational inhaled drug mosliciguat has demonstrated significant improvements in patients with pulmonary hypertension associated with interstitial lung disease.
Key facts
- •The PHocus phase 2 study met its primary endpoint with a 56.3% placebo-adjusted reduction in pulmonary vascular resistance at 16 weeks.
- •Patients showed a 35.2-meter improvement in six-minute walking distance at 16 weeks, increasing to 52.7 meters at 24 weeks.
- •The ongoing phase 3 PHrontier trial aims to enroll approximately 375 patients to confirm the drug's clinical benefits.
- •Mosliciguat is designed as a dry-powder inhalation to target nitric oxide-insensitive forms of the sGC enzyme.
- •The drug's development is supported by the Institute for Lung Health and the German Center for Lung Research.
The investigational inhaled drug mosliciguat has shown consistent therapeutic effects in a randomized phase 2 study involving patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). The study, known as PHocus, evaluated the drug's ability to reduce pulmonary vascular resistance and improve exercise capacity in patients suffering from this challenging form of pulmonary vascular disease.
By the numbers
Clinical Trial Results
The PHocus study enrolled 135 adults across 87 centers in 20 countries. At the 16-week mark, the trial met its primary endpoint, achieving a 56.3% placebo-adjusted reduction in pulmonary vascular resistance. Researchers noted that the treatment effect was consistent across various subgroups, including those receiving concomitant antifibrotic treatment or PDE5 inhibitors. Beyond vascular resistance, patients experienced improvements in exercise capacity. The six-minute walking distance increased by 35.2 meters compared to placebo at week 16, with that difference expanding to 52.7 meters by week 24 in exploratory analysis. Additionally, researchers observed improvements in NT-proBNP levels and other markers of right-heart function.
Mechanism and Research Background
Mosliciguat is a soluble guanylate cyclase (sGC) activator. Unlike sGC stimulators, which primarily target heme-containing enzymes, mosliciguat is designed to target dysfunctional, nitric oxide-insensitive, and heme-free forms of the enzyme that accumulate in inflamed lung tissue. By delivering the drug as a dry-powder inhalation, researchers aim to restore cGMP signaling locally while minimizing systemic vasodilator effects. The drug's development builds on decades of research into the nitric oxide–sGC–cGMP pathway by the Giessen lung research community. This work previously led to the development of riociguat, the first sGC stimulator approved for other forms of pulmonary hypertension. The clinical translation of mosliciguat is being conducted in collaboration with the Institute for Lung Health, the German Center for Lung Research, and the sponsoring company Pulmovant.
Next Steps in Development
Following the positive phase 2 results, a global phase 3 trial titled PHrontier is already underway. This study plans to enroll approximately 375 patients with PH-ILD to be randomized between mosliciguat and a placebo. The primary endpoint for this larger trial is the change in six-minute walking distance after 24 weeks, with secondary outcomes including time to clinical worsening and further assessments of vascular resistance. Mosliciguat remains an investigational drug and has not yet received regulatory approval for the treatment of PH-ILD.
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This article was independently rewritten by ManyPress editorial AI from reporting originally published by Medical Xpress.
