The long-term, pivotal, phase 3 ADVANCE OUTCOMES study of ralinepag in predominantly pre-treated patients with pulmonary arterial hypertension (PAH) met its primary endpoint and important secondary endpoints with statistical significance

The results support the use of ralinepag as a once-daily oral prostacyclin receptor agonist upon approval by the U.S. Food and Drug Administration (FDA)

Investigational ralinepag combines potent receptor binding affinity with continuous exposure to deliver long-term, durable efficacy, and clinically meaningful outcomes

United Therapeutics Corporation (NASDAQ:UTHR), a public benefit corporation, today announced that The Lancet has published full results of its ADVANCE OUTCOMES study, available here.Ralinepag has not been approved for use in any indication by the FDAand remains investigational for PAH.

Ralinepag reduced the risk of a clinical worsening event by 55% compared with placebo in patients with PAH (hazard ratio 0.45, 95% CI [0.33-0.62]; p<0.0001), meeting the study’s primary endpoint with statistical significance. Ralinepag demonstrated durable efficacy in delaying disease progression during the study, in which 80% of patients were on dual background therapy and 70% of patients were considered World Health Organization (WHO) Functional Class (FC) II at baseline.

Ralinepag achieved statistically significant improvements relative to placebo from baseline to week 28 in change in N-terminal pro-B-type natriuretic peptide (NT-proBNP; 24.3% reduction over placebo; p=0.0013) and six-minute walk distance (6MWD; +20.4 m placebo-corrected difference; p=0.0033), two key secondary endpoints. Ralinepag increased the odds of achieving clinical improvement by 47% (p=0.015) compared to placebo, another important secondary endpoint.

These findings were consistent across all patient subgroups, including time since diagnosis, disease etiology, 6MWD, WHO FC, NT-proBNPlevels, and use of background therapies.

The adverse event profile of ralinepag was consistent with known prostacyclin pathway effects. The most commonly reported adverse events in the ralinepag group were headache, diarrhea, nausea, and myalgia. No new safety signals were observed.

United Therapeutics submitted a New Drug Application for ralinepag to the FDA in June 2026. Ralinepag has not been approved for use in any indication by the FDAand remains investigational for PAH.