BIONEWS
Roivant's Phase 2 readout in the lung scarring form of the disease, a new mechanism hit for a population with no approved targeted therapy, triggers an already launched Phase 3.
Pulmonary hypertension slowly narrows and stiffens the arteries that carry blood from the heart to the lungs, forcing the right ventricle to work harder and often ending in heart failure. On Tuesday, a 16-week mid-stage study of Roivant's Pulmovant subsidiary's inhaled drug mosliciguat in patients with the form of the disease tied to interstitial lung disease hit its primary endpoint with a 56.3% placebo-adjusted drop in lung-artery pressure, paired with a 35.2-meter gain in six-minute walk distance and a 53.2% drop in a blood marker of heart strain.
Roivant unveiled a Phase 3 program alongside the readout, the registration path that will need to confirm the Week 16 result before regulators can weigh approval.
The 56.3% figure is a placebo-adjusted reduction in pulmonary vascular resistance (PVR), a hemodynamic measure of how hard blood has to push through the lung arteries. The company called it the largest PVR reduction ever reported in a randomized controlled PH trial, a claim that will need independent benchmarking against historical studies of drugs like inhaled treprostinil and riociguat. The 35.2-meter improvement in six-minute walk distance is a more patient-facing number. It is the standard but imperfect clinical endpoint regulators have used in PH approvals for two decades. The 53.2% drop in NT-proBNP, a peptide the heart releases under strain, is a biomarker that suggests the right ventricle is being asked to do less work. All three reached statistical significance at Week 16 (p<0.0001, p=0.0027, p=0.0002 respectively).
PH-ILD, or pulmonary hypertension associated with interstitial lung disease, is a Group 3 form of the disease that complicates the broad category of lung-scarring conditions including idiopathic pulmonary fibrosis. Existing drugs for pulmonary arterial hypertension, the better-known Group 1 form, like inhaled treprostinil and oral riociguat, are sometimes tried off-label, but none is approved specifically for PH-ILD. Inhaled treprostinil in particular can worsen cough, a problem for a population whose disease already fills the lungs with irritation. Riociguat, like mosliciguat, targets soluble guanylate cyclase (sGC), the enzyme that produces the molecule blood vessels use to relax. Mosliciguat is described as an activator rather than a stimulator of that enzyme, a different chemical approach within the same nitric-oxide signaling pathway.
Cough, the symptom that often limits inhaled PH therapies, was less common on mosliciguat (12.1%) than on placebo (18.2%). The Pulmovant release described the drug as "well tolerated" with a "favorable safety profile" but did not include a full safety table. That detail will arrive with the conference presentation, expected at ERS or CHEST, or in a peer-reviewed publication. Pre-specified Week 24 exploratory results, reported with nominal p-values because the study was not powered for them at 24 weeks, showed the effect sustained: six-minute walk distance still up 52.7 meters and NT-proBNP down 75.9%.
Pulmovant has unveiled the Phase 3 PHrontier study in PH-ILD, and the registration path will be weighed against endpoints that did not appear in Tuesday's readout: clinical worsening, hospitalization, and mortality. Mid-stage readouts in pulmonary hypertension have a long history of late-stage disappointment, and a 16-week hemodynamic and walking result is not a clinical-outcome result. For a population that has had no approved targeted therapy, mosliciguat is one of the first credible new mechanisms the field has delivered in years. The next milestone is whether the Phase 3 design can confirm what the 16-week readout suggested, and whether the cough signal holds up at scale. Independent trade coverage of the readout is also available from STAT+ and a Grafa summary.