Hemodynamic Effects of the Oral Prostacyclin (IP) Receptor Agonist Ralinepag in Pulmonary Arterial Hypertension
CHEST(2017)
Abstract
SESSION TITLE: Late-Breaking Abstracts SESSION TYPE: Late-Breaking Abstract Slide PRESENTED ON: Wednesday, November 1, 2017 at 02:45 PM - 04:15 PM PURPOSE: Targeting the prostacyclin pathway is a central part of pulmonary arterial hypertension (PAH) management, although inconvenience and side effects remain issues. Ralinepag is an oral, non-prostanoid, 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. We evaluated the efficacy, safety, and tolerability of ralinepag in a multinational double-blind Phase 2 study. METHODS: Adults with stable functional class (FC) II-IV PAH and 6-minute walk distance (6MWD) of 100-500 m were enrolled. All subjects were receiving background PAH treatment with an endothelin receptor antagonist, phosphodiesterase type-5-inhibitor, or soluble guanylate cyclase activator, alone or in combination. Subjects were randomized 2:1 to receive ralinepag (40 subjects) or placebo (21 subjects) in a 9-week titration phase followed by 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 the end of treatment. The primary efficacy endpoint was change in pulmonary vascular resistance (PVR) from BL to Week 22. Additional analyses included changes in 6MWD, hemodynamics, and safety and tolerability. RESULTS: Enrolled subjects had FC II/III/IV (56%/42%/2%) PAH and mean (standard deviation) 6MWD of 378 m (104 m). BL median PVR was 705 (ralinepag) and 480 (placebo) dyn.s.cm-5. Thirty-five percent of ralinepag subjects and 52% of placebo subjects were receiving background monotherapy; 65% and 48%, respectively, were receiving dual combination therapy. Ralinepag improved median PVR by 163.9 dyn.s.cm-5 from BL, compared with 0.7 dyn.s.cm-5 worsening with placebo (P=0.02). Subjects receiving ralinepag had a 29.8% improvement in PVR compared with placebo (P=0.03) and a 20.1% improvement from BL. 6MWD increased by 36.2 m in the ralinepag group, which was not significantly different from placebo. There were 2 deaths, both in the placebo group. Serious adverse events (AEs) occurred in 10% of ralinepag subjects and 28.6% of placebo subjects. The most common treatment-emergent AEs were as expected for prostacyclin receptor agonists. CONCLUSIONS: Ralinepag significantly improved PVR compared with placebo in subjects with FC II-IV PAH on single or dual background therapy. CLINICAL IMPLICATIONS: Targeting the IP receptor with ralinepag may provide clinical benefit in patients with PAH. DISCLOSURE: Fernando Torres: Consultant fee, speaker bureau, advisory committee, etc.: Consultant fee, speaker bureau, advisory committee, etc Harrison Farber: Consultant fee, speaker bureau, advisory committee, etc.: Consultant fee, speaker bureau, advisory committee, etc Arsen Ristić: Consultant fee, speaker bureau, advisory committee, etc.: Consultant fee, speaker bureau, advisory committee, etc Vallerie McLaughlin: Consultant fee, speaker bureau, advisory committee, etc.: Consultant fee, speaker bureau, advisory committee, etc John Adams: Employee: Employee of Arena Pharmaceuticals Jinkun Zhang: Employee: Employee of Arena Pharmaceuticals Preston Klassen: Employee: Employee of Arena Pharmaceuticals Pilar Escribano Subías: Consultant fee, speaker bureau, advisory committee, etc.: Consultant fee, speaker bureau, advisory committee, etc Namita Sood: Consultant fee, speaker bureau, advisory committee, etc.: Consultant fee, speaker bureau, advisory committee, etc Lewis Rubin: Consultant fee, speaker bureau, advisory committee, etc.: Consultant fee, speaker bureau, advisory committee, etc The following authors have nothing to disclose: Anne Keogh Ralinepag is being investigated for the treatment of pulmonary arterial hypertension
MoreTranslated text
Key words
receptor agonist ralinepag,pulmonary arterial hypertension,arterial hypertension,oral prostacyclin
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined