ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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The SPECTRA Study: A Phase 2a Single-Arm, Open-Label, Multicenter Exploratory Study to Assess the Effects of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (PAH)
Session Title
D3 - D003 COME TOGETHER - CLINICAL ADVANCES IN PULMONARY HYPERTENSION: LESSONS FROM BEST ABSTRACTS
Abstract
A1187 - The SPECTRA Study: A Phase 2a Single-Arm, Open-Label, Multicenter Exploratory Study to Assess the Effects of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (PAH)
Author Block: A. B. Waxman1, M. G. Risbano2, R. P. Frantz3, S. Manimaran4, J. Lu4, F. Rischard5; 1Brigham and Women's Hospital, Boston, MA, United States, 2University of Pittsburgh, Pittsburgh, PA, United States, 3Mayo Clinic, Rochester, NY, United States, 4Acceleron Pharma, Cambridge, MA, United States, 5University of Arizona, Tucson, AZ, United States.
Background: PAH is characterized by pulmonary vascular remodeling, resulting in increased pulmonary artery pressure (PAP) and progressive right ventricular (RV) dysfunction. Disruptions in transforming growth factor (TGF)-β and bone morphogenetic protein (BMP) signaling are associated with PAH. Novel therapies are needed that target these underlying mechanisms of vascular remodeling to attenuate disease development and progression. Sotatercept is a novel first-in-class fusion protein that is proposed to act by rebalancing signaling between these pro-and anti-proliferative pathways. Preclinically, sotatercept has been shown to reverse vascular muscularization, normalize PAP, and improve both RV hypertrophy and RV function. The PULSAR study (NCT03496207) released positive topline results earlier this year. The SPECTRA study (NCT03738150) is an ongoing novel exploratory study designed to evaluate the effects of sotatercept by invasive cardiopulmonary exercise testing (iCPET). Methods: Eligible patients were enrolled with: WHO Group 1 PAH functional class III; age ≥18; baseline pulmonary vascular resistance of ≥4 Wood units by right heart catheterization; 6-minute walk distance of 100-550 meters; stable PAH standard of care (SOC) therapy (double or triple therapy). Sotatercept was administered by subcutaneous injection every 3 weeks for a 24-week treatment period; 0.3mg/kg sotatercept+SOC for cycle 1 and escalating to 0.7mg/kg sotatercept+SOC at cycle 2 and for the remainder of the treatment period. Upright cycle iCPET was performed at baseline and 24 weeks. Primary endpoint was in VO2 max change from baseline at 24-weeks; secondary endpoints included changes from baseline in various exercise and hemodynamic measures obtained from iCPET. Results: Preliminary data as of 07Oct2020 were available on 10 patients. Peak exercise hemodynamic parameters from iCPET are shown in Table 1. Improvements were seen in mean change from baseline to week-24 in VO2 max, ventilatory efficiency (VE/VCO2 slope), total workload, arteriovenous O2 content difference (Ca-vO2), and reductions were seen in mean change from baseline in mPAP, PAWP, and mRAP. Nine patients reported at least one treatment-emergent adverse event, with 1 patient discontinuing. Two serious adverse events were reported, both considered not related to study drug. Conclusions: In this preliminary analysis of patients in the ongoing SPECTRA study, encouraging results in hemodynamics and exercise tolerance and capacity were seen. Safety was consistent with previous reports in PAH and other patient populations. These results further highlight the clinical efficacy of sotatercept and its potential as a new treatment option for PAH patients.
Author Block: A. B. Waxman1, M. G. Risbano2, R. P. Frantz3, S. Manimaran4, J. Lu4, F. Rischard5; 1Brigham and Women's Hospital, Boston, MA, United States, 2University of Pittsburgh, Pittsburgh, PA, United States, 3Mayo Clinic, Rochester, NY, United States, 4Acceleron Pharma, Cambridge, MA, United States, 5University of Arizona, Tucson, AZ, United States.
Background: PAH is characterized by pulmonary vascular remodeling, resulting in increased pulmonary artery pressure (PAP) and progressive right ventricular (RV) dysfunction. Disruptions in transforming growth factor (TGF)-β and bone morphogenetic protein (BMP) signaling are associated with PAH. Novel therapies are needed that target these underlying mechanisms of vascular remodeling to attenuate disease development and progression. Sotatercept is a novel first-in-class fusion protein that is proposed to act by rebalancing signaling between these pro-and anti-proliferative pathways. Preclinically, sotatercept has been shown to reverse vascular muscularization, normalize PAP, and improve both RV hypertrophy and RV function. The PULSAR study (NCT03496207) released positive topline results earlier this year. The SPECTRA study (NCT03738150) is an ongoing novel exploratory study designed to evaluate the effects of sotatercept by invasive cardiopulmonary exercise testing (iCPET). Methods: Eligible patients were enrolled with: WHO Group 1 PAH functional class III; age ≥18; baseline pulmonary vascular resistance of ≥4 Wood units by right heart catheterization; 6-minute walk distance of 100-550 meters; stable PAH standard of care (SOC) therapy (double or triple therapy). Sotatercept was administered by subcutaneous injection every 3 weeks for a 24-week treatment period; 0.3mg/kg sotatercept+SOC for cycle 1 and escalating to 0.7mg/kg sotatercept+SOC at cycle 2 and for the remainder of the treatment period. Upright cycle iCPET was performed at baseline and 24 weeks. Primary endpoint was in VO2 max change from baseline at 24-weeks; secondary endpoints included changes from baseline in various exercise and hemodynamic measures obtained from iCPET. Results: Preliminary data as of 07Oct2020 were available on 10 patients. Peak exercise hemodynamic parameters from iCPET are shown in Table 1. Improvements were seen in mean change from baseline to week-24 in VO2 max, ventilatory efficiency (VE/VCO2 slope), total workload, arteriovenous O2 content difference (Ca-vO2), and reductions were seen in mean change from baseline in mPAP, PAWP, and mRAP. Nine patients reported at least one treatment-emergent adverse event, with 1 patient discontinuing. Two serious adverse events were reported, both considered not related to study drug. Conclusions: In this preliminary analysis of patients in the ongoing SPECTRA study, encouraging results in hemodynamics and exercise tolerance and capacity were seen. Safety was consistent with previous reports in PAH and other patient populations. These results further highlight the clinical efficacy of sotatercept and its potential as a new treatment option for PAH patients.
