SILVER SPRING, Maryland & RESEARCH TRIANGLE PARK, North Carolina, Aug 24, 2026
United Therapeutics Corporation announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for ralinepag for the treatment of adults with pulmonary arterial hypertension (PAH). The FDA has established June 24, 2027, as the Prescription Drug User Fee Act (PDUFA) target action date, marking an important regulatory milestone for the investigational therapy. If approved, ralinepag could become a once-daily oral prostacyclin receptor agonist for PAH, potentially offering an additional treatment option for patients living with the progressive and life-threatening pulmonary vascular disease. Ralinepag has not been approved by the FDA for any indication and remains investigational for PAH.
FDA Accepts Ralinepag Application for PAH
The acceptance of the NDA moves ralinepag into formal FDA review following the completion of its late-stage clinical development program. The application is supported by results from the pivotal Phase 3 ADVANCE OUTCOMES study, a global, randomized, double-blind, placebo-controlled, event-driven trial involving 687 patients with PAH. Participants received individualized, once-daily ralinepag or placebo in addition to standard PAH-specific background therapy, with dosing titrated according to tolerability and clinical response. The study achieved its primary endpoint, with ralinepag demonstrating a statistically significant 55% reduction in the risk of clinical worsening compared with placebo in a predominantly pre-treated PAH population. The clinical worsening endpoint included events such as death, nonelective hospitalization related to worsening PAH, initiation of prostacyclin pathway therapy for worsening disease, disease progression, or an unsatisfactory long-term clinical response. The FDA’s June 24, 2027 PDUFA date provides the target timeline for the agency’s regulatory decision.
Phase 3 Data Show Reduced Clinical Worsening
Beyond the primary endpoint, ADVANCE OUTCOMES generated additional findings supporting the development of ralinepag. The investigational therapy produced statistically significant improvements in NT-proBNP, a biomarker associated with cardiac stress and heart failure, as well as six-minute walk distance (6MWD), an established measure of exercise capacity in PAH clinical studies. Ralinepag also increased the odds of achieving clinical improvement by 47%, according to the company. United Therapeutics reported that these findings were consistent across patient subgroups, including different disease etiologies, baseline exercise capacity, World Health Organization Functional Class, NT-proBNP levels and background PAH therapies. The reported safety profile was described as consistent with known prostacyclin-related adverse events, with no new safety signals identified during the study. These findings have also been presented at the 2026 American Thoracic Society annual meeting and published in The Lancet, providing additional scientific visibility for the Phase 3 program.
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Ralinepag Targets Prostacyclin Signaling in PAH
Ralinepag is a highly selective prostacyclin IP receptor agonist designed to restore prostacyclin signaling, an important pathway involved in pulmonary vascular function. Activation of IP receptors on pulmonary artery endothelial and smooth muscle cells promotes downstream cyclic AMP signaling, which can contribute to vasodilation and inhibition of vascular remodeling. United Therapeutics states that ralinepag combines potent IP receptor activity with sustained exposure, supporting its once-daily dosing approach. Earlier Phase 2 research showed that ralinepag reduced pulmonary vascular resistance in patients receiving either single- or dual-agent background therapy. PAH is characterized by increased pressure in the pulmonary arteries and structural changes in pulmonary blood vessels that place increasing strain on the right side of the heart. As the disease progresses, patients can develop right heart failure and potentially death, highlighting the need for therapies capable of slowing disease progression and improving functional outcomes. The FDA filing acceptance represents a significant milestone in United Therapeutics’ PAH development strategy, with the regulatory review now underway and a decision targeted for June 2027. While the Phase 3 results provide encouraging evidence of ralinepag’s potential to reduce clinical worsening and improve selected measures of disease status, final approval and labeling remain subject to FDA review. If approved, ralinepag could expand the therapeutic options available to adults with PAH through its once-daily oral administration and prostacyclin pathway mechanism.
Source: United Therapeutics press release
