Ralinepag — an investigational prostacyclin receptor agonist — has achieved 55% reduction in risk of clinical worsening compared to placebo in patients with pulmonary arterial hypertension (PAH). That’s according to a press release from United Therapeutics Corporation who funded the phase 3 ADVANCE OUTCOMES study.
As the first and only once-daily, extended release oral prostacyclin, ralinepag restores prostacyclin signaling and activates pathway receptors to mitigate its impact on the progression of PAH. Results of the study were announced in March 2026 and presented in May 2026 at the American Thoracic Society (ATS) International Conference.
The international study included 687 adult patients with PAH from 30 countries across five continents. In addition to standard PAH background therapies, participants randomly received placebo or ralinepag titrated for tolerability and response. Of the participants, 80% were on dual background therapy and 70% were considered World Health Organization/New York Heart Association Functional Class II (low risk) at baseline.
United Therapeutics reported that ralinepag demonstrated durable efficacy in delaying disease progression and met its primary endpoint of time to first indication of clinical worsening. Researchers also observed statistically significant improvements relative to placebo in secondary endpoints, including six-minute walk distance (6MWD) and change in N-terminal pro-B-type natriuretic peptide, with ralinepag increasing clinical improvement odds by 47% from baseline to week 28 (p=0.015).
Benefits were consistent across patient subgroups, including disease etiology, time since diagnosis, use of background therapies and baseline 6MWD. While most participants (>90%) who received ralinepag reported an adverse event, only about 5% experienced serious drug-related adverse events. The overall safety profile of the drug showed it was well-tolerated with a positive risk-benefit ratio.
Study lead author Vallerie V. McLaughlin, MD, professor of cardiovascular medicine and director of the Pulmonary Hypertension Program at the University of Michigan in Ann Arbor, presented the findings at the ATS meeting. She said ralinepag builds on other available oral prostacyclin pathway agents by providing higher potency and longer half-life, which reinforces the drug’s efficacy and potential broad therapeutic relevance.
Dr. McLaughlin also said the significant reduction in clinically worsening events suggests ralinepag should be introduced earlier in low-risk patients. Its ability to effectively target the prostacyclin pathway could reduce the need for additional or more invasive prostacyclin treatments, she said.
United Therapeutics said it plans to submit a New Drug Application (NDA) for ralinepag to the U.S. Food and Drug Administration (FDA) by the second half of 2026.
