Thorax: New inhaled drug improves blood flow in the lungs and exercise capacity in patients with pulmonary hypertension

The experimental inhaled drug mosliciguat significantly reduced pulmonary vascular resistance and improved exercise capacity in patients with pulmonary hypertension associated with interstitial lung disease. These were the findings of the international phase 2 PHocus trial, which involved 135 patients from 20 countries.

The results of the study were published in the journal Thorax.

Pulmonary hypertension associated with interstitial lung disease is one of the most challenging conditions in pulmonology. In this condition, damage and scarring of lung tissue are accompanied by changes in the blood vessels, making it more difficult for the heart to pump blood through the lungs.

Mosliciguat belongs to a new class of drugs known as soluble guanylate cyclase (sGC) activators. It acts on the nitric oxide signaling pathway, which plays an important role in regulating blood vessel tone.

Unlike drugs that stimulate normally functioning sGC, sGC activators can also act on damaged forms of the enzyme that accumulate during oxidative stress and chronic inflammation. Mosliciguat is delivered directly to the lungs as a dry powder. This method of administration is intended to target the pulmonary blood vessels directly and reduce the drug's effects on blood vessels in other organs.

In the PHocus trial, patients received either mosliciguat or a placebo. After 16 weeks, pulmonary vascular resistance in participants receiving the drug was 56.3% lower than in the placebo group after adjustment for baseline values.

The effect was consistent across various prespecified patient subgroups, including those with different forms of interstitial lung disease and different degrees of vascular involvement.

The changes were not limited to measures of blood flow. After 16 weeks, patients receiving mosliciguat walked an average of 35.2 meters farther during the six-minute walk test than those in the placebo group. In an additional analysis at 24 weeks, the difference reached 52.7 meters.

The researchers also reported improvements in NT-proBNP levels, a biomarker used to assess cardiac strain, as well as in other measures of right-heart and pulmonary vascular function.

The phase 2 results build on an earlier phase 1 study, in which a single inhalation of mosliciguat also led to a sustained reduction in pulmonary vascular resistance. Most reported adverse events were mild, and no clinically significant changes in systemic vascular resistance or blood pressure were observed.

The next step will be the phase 3 PHrontier clinical trial, which has already begun. It is expected to enroll approximately 375 patients with pulmonary hypertension associated with interstitial lung disease. The primary efficacy endpoint will be the change in the distance patients can walk in six minutes after 24 weeks of treatment.