On a quiet morning in Giessen, Germany, a 62-year-old patient with a rare and worsening lung disease inhaled a fine powder through a small device—and took a step forward that researchers have been working toward for decades. That breath carried mosliciguat, an experimental drug now showing powerful results in treating pulmonary hypertension linked to interstitial lung disease (PH-ILD), a condition that slowly starves the lungs of oxygen and overwhelms the heart.
PH-ILD is one of the most difficult forms of pulmonary hypertension, with few effective treatments. It arises when scarred, stiff lung tissue strains the delicate blood vessels in the lungs, forcing the heart to pump harder. Over time, this can lead to heart failure. But in a major clinical trial called PHocus, mosliciguat—a drug designed to target damaged lung vessels directly—has shown it can reverse some of this strain.
The trial included 135 adults across 20 countries and 87 medical centers. After 16 weeks, patients who inhaled mosliciguat saw their lung blood vessel resistance drop by 56.3% more than those on placebo—a dramatic shift in a disease where even small improvements matter. Their ability to walk also got better: they covered 35.2 meters (115 feet) farther in six minutes by week 16, and that gap grew to 52.7 meters (173 feet) by week 24. Blood tests showed less strain on the heart, and side effects were mostly mild.
What makes mosliciguat different is how it works. Most drugs act on healthy blood vessel pathways, but mosliciguat targets damaged ones—specifically, the broken enzyme systems in lung vessels harmed by chronic inflammation and scarring. By activating a key enzyme called soluble guanylate cyclase (sGC) even when it’s no longer responsive to natural signals, the drug restores a vital chemical signal that relaxes blood vessels. And because it’s inhaled, it acts mostly in the lungs, reducing the risk of dangerous drops in blood pressure elsewhere in the body.
This breakthrough didn’t happen overnight. It’s the result of over 30 years of research in Giessen, where scientists first helped prove that boosting the nitric oxide–sGC–cGMP pathway could treat lung vascular disease. That earlier work led to riociguat, the first approved drug in this class, which won Germany’s top science prize in 2015. Now, mosliciguat extends that legacy into a new disease area.
"Mosliciguat now takes this principle into a biologically distinct disease setting and represents precisely the kind of long-term bench-to-bedside research that the Institute for Lung Health and the German Center for Lung Research were created to enable," said Dr. Werner Seeger, a leading voice in lung research.
With phase 3 trials on the horizon, this inhaled therapy could soon offer new hope to thousands living with PH-ILD—proof that patient by patient, breath by breath, science can open new paths where none seemed possible.