ADVANCE OUTCOMES: United Therapeutics Reports 55% Risk Reduction with Ralinepag

United Therapeutics reported in its ADVANCE OUTCOMES release that the long-term pivotal phase 3 ADVANCE OUTCOMES trial of the oral prostacyclin (IP) receptor agonist ralinepag in pulmonary arterial hypertension (PAH) met its primary endpoint versus placebo, with a stated 55% reduction in the risk of a first adjudicated clinical worsening event over time (HR 0.45, 95% CI 0.33–0.62; p<0.0001). The company described this as a delay in disease progression during the study. The same release also summarized secondary endpoint findings, a tolerability overview, and planned dissemination and regulatory steps.

United Therapeutics described the enrolled population as patients with PAH who were predominantly pre-treated, noting that at baseline 80% of participants were receiving dual background therapy and 70% were World Health Organization (WHO)/New York Heart Association (NYHA) Functional Class (FC) II. In the same communication, the company stated that the primary endpoint effect was reported as consistent across patient subgroups, including time since diagnosis, disease etiology, baseline six-minute walk distance, and use of background therapies. The release then shifted to prespecified secondary measures assessed during follow-up.

For secondary endpoints, the release reported statistically significant improvements versus placebo in six-minute walk distance and change in N-terminal pro-B-type natriuretic peptide (NT-proBNP), without providing effect magnitudes in the summary language. United Therapeutics also reported that ralinepag increased the odds of achieving clinical improvement by 47% from baseline to Week 28 (p=0.015). Overall, the company reported statistically significant differences versus placebo across several secondary endpoints in the ralinepag group.

On safety and tolerability, United Therapeutics described treatment with ralinepag as well-tolerated. The company stated that the safety profile was consistent with known prostacyclin-related adverse events and that no new safety signals were observed. This was presented as the tolerability snapshot accompanying the efficacy readout.

The release stated that participants who completed the study could enter an ongoing open-label extension study, ADVANCE EXTENSION. United Therapeutics also stated its intent to submit a New Drug Application for ralinepag to the U.S. Food and Drug Administration in the second half of 2026 and said it plans to present full results at an upcoming international conference. In addition, the company noted it hosted a public webcast on March 2, 2026, with a rebroadcast available for one year via its investor events and presentations page, summarizing the dissemination approach described alongside the regulatory timeline.

Key Takeaways:

• United Therapeutics reported a reduction in risk/time-to-event for time to first adjudicated clinical worsening with ralinepag versus placebo in the phase 3 ADVANCE OUTCOMES trial.
• The company also reported statistically significant secondary endpoint findings for six-minute walk distance, NT-proBNP, and odds of clinical improvement at Week 28.
• The release described ralinepag as well-tolerated and reported no new safety signals.
• The release also outlined an NDA submission intent for the second half of 2026, along with plans to present full results at an upcoming international conference and to provide webcast replay access.