Regulatory & Policy

FDA accepts United Therapeutics' ralinepag NDA for PAH

FDA accepts United Therapeutics' ralinepag NDA for PAH

The US FDA has accepted for review a New Drug Application from United Therapeutics Corporation (Nasdaq: UTHR) for ralinepag, an investigational prostacyclin IP receptor agonist intended to treat pulmonary arterial hypertension (PAH). The agency has set a Prescription Drug User Fee Act (PDUFA) target action date of June 24, 2027.

The filing rests on results from the Phase III ADVANCE OUTCOMES study, in which ralinepag reduced the risk of a first clinical worsening event by 55% compared with placebo (hazard ratio 0.45, 95% CI [0.33–0.62]; p<0.0001) in 687 predominantly pre-treated patients. The trial population was notable for its relatively preserved baseline functional status — 70% of patients were World Health Organization Functional Class (WHO FC) II and 80% were on dual background therapy. Ralinepag also demonstrated statistically significant improvements in N-terminal pro-B-type natriuretic peptide (NT-proBNP; 24.3% reduction over placebo; p=0.0013) and six-minute walk distance (6MWD; +20.4 m placebo-corrected difference; p=0.0033), and increased the odds of clinical improvement by 47% (p=0.015). The full results were published in The Lancet in July 2026.

The safety profile was consistent with known prostacyclin-related adverse events — primarily headache, diarrhea, nausea, and myalgia — and the company said no new safety signals were observed.

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United states that ralinepag would be the first once-daily oral prostacyclin IP receptor agonist available for PAH if approved. The current oral options in the prostacyclin class are selexipag (Uptravi), which requires twice-daily dosing, and oral treprostinil (Orenitram), which requires multiple daily doses taken with food. Merck's sotatercept (Winrevair), approved in 2024 via a distinct activin signaling mechanism, has added a new layer of competition in the class, but does not directly overlap with the prostacyclin pathway.

In May 2026, the company and MannKind Corporation (Nasdaq: MNKD) announced development of a dry powder inhalation formulation of ralinepag (MNKD-1501) for PAH and fibrotic lung diseases, with MannKind eligible for up to USD 35 million in development milestones. United said it plans to file an investigational new drug application for ralinepag DPI later in 2026.


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