ELEVATE 2: Baseline Demographic Characteristics From the Phase IIB Study of the Efficacy and Safety of Two Doses of Rodatristat Ethyl When Added to Standard of Care for the Treatment of Pulmonary Arterial Hypertension

Abstract

Background: Pulmonary arterial hypertension (PAH) is a rare progressive disease characterized by elevated resting mean pulmonary artery pressure and right ventricular hypertrophy. Platelet‐derived serotonin and serotonin produced in the lung induce excessive growth of pulmonary artery smooth muscle cells and is associated with the development of PAH. Tryptophan Hydroxylase 1 (TPH1) is necessary for serotonin synthesis and is overexpressed in pulmonary artery endothelial cells of PAH patients. Rodatristat ethyl is an investigational, orally administered prodrug for rodatristat, a potentTPH1 inhibitor, and potential first‐in‐class treatment for PAH. In the pulmonary vasculature, rodatristat may inhibit both receptor and serotonin transporter functions, with potential to reduce proliferation and contraction of pulmonary artery smooth muscle cells. Importantly, rodatristat ethyl was designed tonot cross the blood brain barrier. Interim blinded baseline demographic data from the ongoing Phase IIbstudy, ELEVATE 2 (NCT04712669), is summarized here in. Methods: ELEVATE 2 is a double blind, placebo‐controlled study in which Group 1 PAH patients were randomized 1:1:1 to receive placebo, 300 mg BID, or 600 mg BID of rodatristat ethyl in addition to standard of care (SOC) PAH treatment for a period of 24 weeks followed by an optional open‐label extension (OLE). The primary end point is change in pulmonary vascular resistance (PVR) from baseline.The trial included patients age ≥18 years, functional class (FC) II‐III, and six‐minute walk distance(6MWD) between 100‐ 550m and PVR of ≥350 dyn. sec.cm‐5 at baseline. Results: Baseline characteristics are summarized in Table 1. At the time of this analysis, 90 patients were randomized in the study; 37 patients completed the main study, 35 enrolled in the OLE, and 6completed the first 24 weeks of the OLE. The mean age was 53 years, 79% of the study population waswhite, and 76% of patients identified as female. The mean 6MWD was 420 m at baseline and 66% were classified as WHO FC II. Baseline pulmonary vascular resistance was 668 dyn. sec.cm‐5. Patients receiving three SOC drugs at randomization represented 51% of the trial population and 29% were on a continuous infusion of a prostanoid. Conclusions: In this first report of ELEVATE 2, demographic data are broadly consistent with previously reported PAH clinical trial patient populations. Patients were stratified based on mono, dual, or tripleSOC therapies which could include a continuous infusion of a prostanoid. (Table Presented).