Conference: 2018 PHA International PH Conference & Scientific Sessions
Release Date: 06.28.2018
Presentation Type: Abstracts
File Download: Conference 2018_5056
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Abstract presented at the 2018 International PH Conference and Scientific Sessions in Orlando, Fla., June 28-July 1, 2018.
To evaluate the efficacy, safety, and tolerability of ralinepag in a multinational double-blind Phase 2 study.
Ralinepag is a novel, next-generation, oral, highly selective IP receptor agonist with optimized receptor activation and a half-life of ~24 hours. Ralinepag has antiproliferative and vasodilatory activities on pulmonary smooth muscle cells and pulmonary arteries.
Adults with stable functional class (FC) II–IV PAH and 6-minute walk distance (6MWD) of 100–500 m, on single or dual background PAH treatment, were randomized 2:1 to receive ralinepag (n=40) or placebo (n=21) for 9 weeks of titration, then 13-week maintenance. Treatment was initiated at 10 µg twice daily (bid) and titrated weekly up to 300 µg bid, as tolerated. Right heart catheterization was performed at baseline (BL) and at 22 weeks. The primary efficacy endpoint was change in pulmonary vascular resistance (PVR) from BL to Week 22. Additional analyses included changes in 6MWD, hemodynamics, safety and tolerability.
Patients were FC II/III/IV (56%/43%/2%) with mean 6MWD of 378±104 m (SD). BL median PVR was 705 (ralinepag) and 480 (placebo) dyn·s·cm–5. 35% of ralinepag patients and 52% of placebo patients were receiving background monotherapy; 65% and 48%, respectively, were receiving dual therapy. Ralinepag reduced median PVR by 163.9 dyn·s·cm–5 from BL, compared with a 0.7 dyn·s·cm-5 increase on placebo (P=0.02). Patients receiving ralinepag had a 29.8% reduction in PVR compared with placebo (P=0.03), and a 20.1% reduction from BL. 6MWD increased by 36.2 m in the ralinepag group, which was not significantly different from placebo. There were two deaths, both in the placebo group. Serious adverse events (AEs) occurred in 10% of patients on ralinepag and 29% of those on placebo. The most common treatment-emergent AEs were as expected for IP receptor agonists.
Ralinepag significantly reduced PVR compared with placebo in patients with FC II–IV Group 1 PAH on single or dual background therapy.