SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C., July 29, 2026
United Therapeutics Corporation announced that the complete results from its pivotal Phase 3 ADVANCE OUTCOMES study evaluating investigational ralinepag for pulmonary arterial hypertension (PAH) have been published in The Lancet, highlighting statistically significant improvements in both the primary and key secondary endpoints. The long-term global study demonstrated that ralinepag reduced the risk of clinical worsening by 55% compared with placebo, providing strong evidence for its potential use as a once-daily oral prostacyclin receptor agonist pending U.S. Food and Drug Administration (FDA) approval. The company previously submitted a New Drug Application (NDA) for ralinepag to the FDA in June 2026, with the therapy currently remaining investigational.
Phase 3 Trial Demonstrates Durable Clinical Benefits
The ADVANCE OUTCOMES study enrolled 687 patients with PAH in a randomized, double-blind, placebo-controlled, event-driven Phase 3 trial conducted across multiple global sites. Approximately 80% of participants were already receiving dual background therapy, while 70% were classified as WHO Functional Class II, representing a predominantly pre-treated patient population. The trial successfully met its primary endpoint, with ralinepag lowering the risk of a first clinical worsening event by 55% compared with placebo (hazard ratio 0.45; p<0.0001). Additionally, the therapy achieved statistically significant improvements in important secondary endpoints, including a 24.3% reduction in NT-proBNP levels, a 20.4-meter placebo-corrected improvement in six-minute walk distance (6MWD), and a 47% increase in the likelihood of achieving clinical improvement. These benefits remained consistent across multiple patient subgroups regardless of disease severity, treatment history, or baseline functional status.
Safety Profile Supports Once-Daily Oral Therapy
The safety findings from the Phase 3 trial were consistent with the established prostacyclin pathway, with headache, diarrhea, nausea, and myalgia reported as the most common treatment-related adverse events. Importantly, no new safety signals were identified, reinforcing the therapy’s favorable risk-benefit profile. Ralinepag is a highly selective non-prostanoid prostacyclin IP receptor agonist designed to provide continuous receptor activation through sustained drug exposure, delivering durable vasodilatory, anti-proliferative, and anti-inflammatory effects. Unlike existing therapies that may require more complex administration, the investigational medicine is designed as a once-daily oral treatment, potentially offering greater convenience while maintaining long-term clinical efficacy for patients living with this progressive and life-threatening disease.
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Publication Strengthens Regulatory Momentum for Ralinepag
Publication of the ADVANCE OUTCOMES study in The Lancet, one of the world’s leading peer-reviewed medical journals, represents an important scientific milestone for United Therapeutics as the company advances ralinepag through regulatory review. Pulmonary arterial hypertension remains a serious rare disease that progressively damages the pulmonary arteries and ultimately leads to right heart failure despite advances in available therapies. Company leadership emphasized that the strong Phase 3 findings demonstrate the potential for ralinepag to improve long-term patient outcomes, particularly in individuals already receiving standard background treatments. With the FDA currently reviewing the NDA submitted in June 2026, the published clinical evidence further supports the therapy’s potential to become a valuable new treatment option for patients with pulmonary arterial hypertension, addressing a significant unmet medical need in rare cardiovascular disease.
Source: United Therapeutics press release
