New Phase 3 trial data show ralinepag met main goal in PAH treatment
Study shows therapy cut risk of clinical worsening by 55% vs placebo
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Following positive results from a Phase 3 clinical study, United Therapeutics plans to submit an application to the U.S. Food and Drug Administration (FDA) by the second half of 2026 seeking approval for its experimental oral therapy ralinepag as a treatment for pulmonary arterial hypertension (PAH).
United announced that the ADVANCE OUTCOMES clinical trial (NCT03626688) had hit its main goal, showing ralinepag outperformed a placebo at reducing the risk of clinical worsening — a composite outcome that includes events such as death, nonelective hospitalization for worsening PAH, and disease progression. The company said it plans to use data from the study to support its FDA approval application.
ADVANCE OUTCOMES trial shows strong results for ralinepag
“United Therapeutics was founded on the idea that we could bring transformative therapies to people living with PAH. Our achievement in this pivotal trial is among the most important in our history and strengthens our decades‑long commitment to advancing prostacyclin‑based science,” Martine Rothblatt, PhD, chairperson and CEO of United, said in a company press release.
According to the company, the ADVANCE OUTCOMES trial enrolled 687 people with PAH who were randomly assigned to receive daily ralinepag or a placebo. Among the participants, about 80% were receiving dual background therapy, and about 70% were classified as functional class 2 at the start of the study, meaning they had no symptoms at rest but experienced issues such as shortness of breath during everyday activities like climbing stairs.
According to United, results showed ralinepag reduced the risk of clinical worsening by 55%. At the same time, the odds of clinical improvement by week 28 (almost seven months) were significantly higher with ralinepag than with the placebo, by about 47%. Ralinepag specifically outperformed the placebo in improving scores on the six-minute walk distance, a standardized test used to measure exercise capacity, and in reducing levels of the heart stress marker N-terminal pro-B-type natriuretic peptide (NT-proBNP), the company said.
“The strength and consistency of these findings give us great optimism that ralinepag could meaningfully improve long‑term outcomes and, if approved, usher in a new era of treatment for PAH that brings us closer than ever to addressing the profound unmet needs that persist in this disease. We are grateful for the essential contributions of the study participants and the investigators whose work underpinned this tremendous result,” Rothblatt said.
Ralinepag benefits seen across patient subgroups
United said the efficacy of ralinepag was consistent across different patient subgroups and noted that no new safety signals were observed in the Phase 3 trial. The company didn’t provide specifics, saying details will be presented at an upcoming medical conference.
“In the ADVANCE OUTCOMES study, ralinepag delayed disease progression in patients with PAH facing significant disease burden at baseline. Ralinepag’s potency and once-daily oral dosing make these outcomes highly relevant in real-world settings,” said Vallerie V. McLaughlin, MD, a professor at the University of Michigan and chair of the ADVANCE OUTCOMES steering committee, who has served as a consultant for United.
