United Therapeutics (UTHR) Study result summary

Study design and population

• Phase III ADVANCE OUTCOMES was a global, randomized, double-blind, placebo-controlled trial in 687 PAH patients, with 1:1 randomization and 80% power to detect a hazard ratio of 0.65.

• Patients received once-daily ralinepag or placebo, in addition to standard PAH background therapy, with individualized dosing.

• The primary endpoint was time to first adjudicated clinical worsening event, a composite including mortality, hospitalization, disease progression, and need for additional therapy.

• Most participants were on dual background therapy (about 80%), predominantly ERA and PDE5 inhibitors, with a mean disease duration of 4.5 years and functional class II or III.

• Stratification included baseline six-minute walk distance and functional class, ensuring a contemporary, well-treated cohort.

Patient demographics and baseline characteristics

• 687 subjects were enrolled: 350 received ralinepag, 337 received placebo.

• Median age was 53 years; 75.7% were female.

• Most patients were White (80.2%) and on dual background PAH therapy (79.8%).

• Mean baseline 6MWD was 438.9 meters; 70.5% were WHO functional class II.

• The study population reflected real-world PAH demographics and current treatment guidelines.

Efficacy results

• Ralinepag reduced the risk of clinical worsening events by 55% compared to placebo (hazard ratio 0.45, 95% CI: 0.33–0.62; p<0.0001), with early and durable separation of Kaplan-Meier curves.

• The primary driver of benefit was a three-fold reduction in disease progression events in the ralinepag group.

• Statistically significant improvements were seen in secondary endpoints, including six-minute walk distance, NT-proBNP, and clinical improvement rates.

• Benefits were consistent across all demographics, background therapies, functional classes, and geographies.

• Clinical worsening occurred in 18.3% of ralinepag patients vs. 35.9% of placebo.