United's PAH drug clears phase 3 trial, setting up filings
United Therapeutics plans to file for approval of ralinepag as a treatment for pulmonary arterial hypertension (PAH) before the end of the year, after positive results in a phase 3 trial.
The drug acts as a prostacyclin receptor agonist, which is a fairly crowded class with several approved oral, intravenous or inhaled therapies. However, United hopes that, as a once-daily oral therapy, ralinepag will be a step up in patient convenience without compromising efficacy.
The results of the placebo-controlled ADVANCE-OUTCOMES study suggest it may be on track to deliver that objective, as ralinepag met its primary objective of lengthening the time to worsening of PAH, a composite of death, hospital admission or the need for IV or inhaled prostacyclin therapy due to worsening PAH, disease progression, or an unsatisfactory long-term clinical response.
There was a 55% improvement on that endpoint compared to placebo, along with encouraging secondary results such as a 47% increased chance of clinical improvement, longer six-minute walk distance (6MWD) test times, and improvements in NT-proBNP levels, a biomarker released when the heart is stressed.
Treatment with ralinepag was well-tolerated, and the safety profile was consistent with known prostacyclin-related adverse events, according to United, which noted that no new safety signals were seen with the drug.
PAH is a life-threatening disease, caused by the narrowing of blood vessels in the lungs, which is currently treated mainly with drugs that dilate the blood vessels, like endothelin antagonists and prostacyclin analogues, as well as phosphodiesterase (PDE) inhibitors that increase blood flow through the lungs.
The market is increasingly crowded, so the commercial potential of ralinepag is open to question, although some analysts have previously said it could have $1 billion-plus potential.
Other oral drugs in the prostacyclin receptor agonist include Johnson & Johnson's $1.9 billion blockbuster Uptravi (selexipag), dosed twice daily, and United's oral drug Orenitram (treprostinil), which needs to be taken three times a day.
Another rival is J&J's Opsynvi (combining endothelin receptor antagonist macitentan and PDE5 inhibitor tadalafil) – another once-daily oral option – which, along with monotherapy Opsumit (macitentan) made sales of $1.1 billion last year.
Beyond those, one of the toughest competitors to ralinepag – if approved – will be MSD's Winrevair (sotatercept), which works by inhibiting activin signalling and achieved sales of $1.4 billion in 2025, its first full year on the market, and is dosed by subcutaneous injection every three weeks.
In a statement, United said ralinepag "has the potential to redefine the PAH treatment landscape as the first and only once-daily oral prostacyclin, combining potent receptor affinity with continuous exposure to deliver long-term, durable efficacy and disease-mitigating outcomes." It intends to file for FDA approval of the drug in the second half of the year.
United acquired rights to ralinepag from Arena Pharma in 2018, in a deal that included an upfront payment of $800 million and up to $400 in milestone payments.
