ADVANCE OUTCOMES is a phase 3, randomised, double-blind trial tested oral ralinepag against placebo in pulmonary arterial hypertension patients, measuring time to first clinical worsening (death, hospitalisation, need for parenteral/inhaled prostacyclin therapy, disease progression, or unsatisfactory clinical response). Patients were enrolled between Jan 24, 2019, and June 20, 2025. Of 1037 patients screened for eligibility, 728 were randomly assigned and received at least one dose of ralinepag or placebo; 687 were included in the full analysis and safety sets, of whom 350 received ralinepag and 337 received placebo.
Key results:
- Clinical worsening occurred in 18% of the ralinepag group vs 36% of the placebo group — a 55% risk reduction (HR 0.45, p<0.0001)
- Ralinepag caused more treatment discontinuations due to side effects (19% vs 3%)
- Serious adverse events and deaths were similar between groups
Bottom line: Ralinepag, an oral once-daily prostacyclin-pathway drug, significantly reduced the risk of disease worsening in pulmonary arterial hypertension patients already on standard therapy, though with a higher rate of tolerability-related discontinuation.
Read more at this link on The Lancet
Citation
Vallerie V McLaughlin, Derek Solum, Daniel Lachant, Ali Ataya, Joan A Barberà, Gisela Bohns Meyer, Sung-A Chang, Richard Channick, Colin Church, John Feenstra, Sean Gaine, George Giannakoulas, Carlos Jerjes-Sanchez, Dinesh Khanna, Nick H Kim, Ronald Oudiz, Ioana R Preston, Namita Sood, Fernando Torres, Jean-Luc Vachiery, Tomás Pulido, Dana Cella, Chunqin Deng, Miluska Escudero, Victoria Lacasse, Leigh Peterson, Raymond Benza, Marc Humbert,
Ralinepag for the treatment of pulmonary arterial hypertension (ADVANCE OUTCOMES): a randomised, double-blind, placebo-controlled phase 3 study, The Lancet, 2026, ISSN 0140-6736, https://doi.org/10.1016/S0140-6736(26)01011-1. (https://www.sciencedirect.com/science/article/pii/S0140673626010111)