Phase III ADVANCE OUTCOMES data presented at ATS 2026 showed investigational once-daily oral therapy ralinepag reduced the risk of clinical worsening by 55% in pulmonary arterial hypertension patients while significantly improving NT-proBNP levels and exercise capacity.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
United Therapeutics Corporation announced full results from the pivotal Phase III ADVANCE OUTCOMES trial (NCT03626688) showing that investigational therapy ralinepag significantly reduced the risk of clinical worsening in patients with pulmonary arterial hypertension (PAH). The findings were presented during the Breaking News: 2026 Clinical Trial Results in Pulmonary Medicine session at the American Thoracic Society (ATS) International Conference in Orlando.
In the global, randomized, placebo-controlled study involving 687 patients with PAH, ralinepag reduced the risk of clinical worsening by 55% compared with placebo (hazard ratio 0.45; 95% CI, 0.33-0.62; p<0.0001), meeting the trial’s primary endpoint.
The treatment effect was consistent across multiple patient subgroups, including disease etiology, six-minute walk distance (6MWD), NT-proBNP levels, functional class, and use of background therapies.
The study population reflected a heavily pretreated PAH setting, with approximately 80% of participants receiving dual background therapy and 70% categorized as WHO/New York Heart Association Functional Class II at baseline.
Investigators reported that ralinepag demonstrated durable efficacy despite the relatively lower-risk profile of many enrolled patients, supporting the potential value of earlier treatment escalation in PAH.
Ralinepag also achieved statistically significant improvements across key secondary endpoints at Week 28, including a 24.3% reduction in NT-proBNP levels versus placebo (p=0.0013), a placebo-corrected 20.4-meter improvement in 6MWD (p=0.0033), and a 47% increase in the odds of achieving clinical improvement (p=0.015).
The safety profile was consistent with known prostacyclin-related adverse events, and investigators observed no new safety signals during the study.
Vallerie V. McLaughlin said the findings showed that ralinepag provided both early and sustained benefit in heavily pretreated PAH patients and suggested that earlier escalation of therapy could help delay progression of the life-threatening disease.
According to Derek Solum, ralinepag demonstrated efficacy across multiple PAH etiologies, including connective tissue disease-associated PAH such as systemic sclerosis. He noted that the therapy’s extended-release pharmacokinetic profile is designed to provide sustained receptor exposure similar to parenteral prostacyclin therapy.
Investigators said the once-daily oral extended-release profile of ralinepag may help bridge the gap between oral prostacyclin pathway therapies and more intensive parenteral prostacyclin treatments by combining sustained receptor activity with the convenience of oral dosing. Upon approval, ralinepag is expected to become the first once-daily oral prostacyclin receptor agonist for PAH.
United Therapeutics said it plans to submit a New Drug Application for ralinepag to the U.S. Food and Drug Administration in the second half of 2026. The therapy remains investigational and has not yet been approved by the FDA.
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About the Writer
Nikita Jha, BPharm (LinkedIn) a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.