Roivant's mosliciguat hits Phase 2 primary endpoint in PH-ILD

Roivant Sciences has reported positive topline results from its Phase 2 PHocus study evaluating mosliciguat in pulmonary hypertension associated with interstitial lung disease (PH-ILD), a progressive condition carrying a median survival of roughly 1.5 to 2 years. The results were presented at the European Respiratory Society International Congress 2026 by Professor Marc Humbert of Université Paris-Saclay.

The 135-patient, randomised, double-blind, placebo-controlled trial, conducted across 87 sites in 20 countries, met its primary endpoint at Week 16: a placebo-adjusted reduction in pulmonary vascular resistance (PVR) of 56.3% (p<0.0001). The company says this is the largest PVR reduction ever reported in a randomised controlled pulmonary hypertension trial. Secondary endpoints were also met, with a placebo-adjusted improvement in six-minute walk distance (6MWD) of 35.2 metres (p=0.0027) and a 53.2% reduction in NT-proBNP, a cardiac strain biomarker (p=0.0002). In a pre-specified exploratory analysis at Week 24, effects continued to strengthen: 6MWD improved by a further 52.7 metres and NT-proBNP fell by 75.9%, both nominally significant.

Mechanism and tolerability

Mosliciguat is positioned as a potential first-in-class, once-daily, inhaled soluble guanylate cyclase (sGC) activator. It is mechanistically distinct from sGC stimulators such as riociguat: rather than requiring the presence of nitric oxide or reduced haem to function, it activates sGC independently of haem status. This may confer an advantage in oxidative-stress conditions such as PH-ILD, where native sGC function is typically impaired.

On safety, the drug was reported to be well tolerated. Notably, the incidence of cough was lower in the mosliciguat arm than in the placebo arm (12.1% versus 18.2%), a relevant finding given that cough is a recognised tolerability issue with inhaled treprostinil, currently the dominant approved therapy in this space. Drew Fromkin, chief executive of Pulmovant, the Roivant subsidiary developing the asset, said the treatment landscape for PH-ILD "is sparse, primarily consisting of formulations of inhaled treprostinil and their associated limitations, and off-label use of PDE5 inhibitors."

Phase 3 and competitive landscape

Roivant has already initiated the Phase 3 PHrontier study in PH-ILD, designed to enrol approximately 375 patients in a 1:1 randomised, double-blind, placebo-controlled design. Moving directly from a positive Phase 2 readout into a registrational study reflects the company's confidence in the dataset and the high unmet need in a population of up to 200,000 patients across the US and Europe who have limited or no approved treatment options.

Group 3 PH, which encompasses PH arising from lung diseases including ILD, has historically been an area of regulatory caution. The FDA declined to approve inhaled treprostinil (Tyvaso) for PH-ILD in its initial review cycle before ultimately granting approval on the basis of the INCREASE trial in 2021. That precedent established that a randomised, placebo-controlled trial with haemodynamic and functional endpoints can support approval in this indication, providing a useful regulatory read-across for PHrontier's design.

The competitive field remains relatively narrow. United Therapeutics' Tyvaso DPI is approved in the US; outside the US, options are more limited. A number of other companies are exploring sGC pathway and PDE5 inhibitor approaches in broader PH populations, but none has reported comparable haemodynamic data in a Group 3-specific trial. If PHrontier replicates the PHocus effect size, mosliciguat would represent a meaningful new option in a space where patients face poor prognoses. Investors and clinicians will watch enrolment pace and the emerging safety database as the next near-term indicators.