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Recent Advances in Chest Medicine |

Riociguat: Mode of action and clinical development in pulmonary hypertension OPEN ACCESS

Hossein-Ardeschir Ghofrani, MD; Marc Humbert, MD; David Langleben, MD; Ralph Schermuly, MD; Johannes-Peter Stasch, PhD; Martin R. Wilkins, MD; James R. Klinger, MD
Author and Funding Information

Funding/Support:

Editorial assistance was provided by Adelphi Communications Ltd (Bollington, UK), supported by Bayer Pharma AG (Berlin, Germany).

Financial/nonfinancial disclosures:

Dr Ghofrani reports grants from Actelion, Bayer HealthCare Pharmaceuticals, Ergonex, and Pfizer; and personal fees from Actelion, Bayer HealthCare Pharmaceuticals, Ergonex, Gilead, GSK, Merck, Novartis, and Pfizer.

Dr Humbert reports personal fees from Actelion, Bayer HealthCare Pharmaceuticals, GSK, Novartis, and Pfizer.

Dr Langleben reports grants, personal fees, and nonfinancial support from Actelion, Bayer HealthCare Pharmaceuticals, Gilead, GSK, and Ikaria.

Dr Schermuly reports grants from Actelion, Bayer HealthCare Pharmaceuticals, Gilead, and Pfizer; and personal fees from Bayer HealthCare Pharmaceuticals and Ergonex.

Dr Stasch is an employee of Bayer Pharma AG, Wuppertal, Germany.

Dr Wilkins reports personal fees and nonfinancial support from Bayer HealthCare Pharmaceuticals.

Dr Klinger reports grants from Actelion, Bayer HealthCare Pharmaceuticals, Gilead, Ikaria, Lung Biotechnology, NIH-NHLBI, Pfizer, and United Therapeutics.

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure and increased pulmonary vascular resistance. If untreated, they can result in death due to right heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. Here we describe in detail the role of the nitric oxide–sGC–cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH, and the mode of action of riociguat. We also review the preclinical data associated with the development of riociguat, along with the efficacy and safety data of riociguat from initial clinical trials and the pivotal Phase III randomized clinical trials in PAH and CTEPH.

1University of Giessen and Marburg Lung Center, Giessen, Germany, member of the German Center for Lung Research (DZL)

2Department of Medicine, Imperial College London, London, UK

3Assistance Publique–Hôpitaux de Paris, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre and Université Paris-Sud, Laboratoire d’Excellence en Recherche sur le Médicament et Innovation Thérapeutique and INSERM Unité 999, Le Kremlin–Bicêtre, France

4Center for Pulmonary Vascular Disease and Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Canada

5Bayer Pharma AG, Wuppertal and University Halle, Institute of Pharmacy, Halle (Saale), Germany

6Division of Pulmonary, Sleep, and Critical Care Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI

Correspondence To: Hossein-Ardeschir Ghofrani, MD, Department of Internal Medicine, Medical Clinic II/V, University Hospital Giessen and Marburg, Klinikstr.33, Giessen 35392, Germany.


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016. doi:10.1016/j.chest.2016.05.024
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Abstract

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure and increased pulmonary vascular resistance. If untreated, they can result in death due to right heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. Here we describe in detail the role of the nitric oxide–sGC–cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH, and the mode of action of riociguat. We also review the preclinical data associated with the development of riociguat, along with the efficacy and safety data of riociguat from initial clinical trials and the pivotal Phase III randomized clinical trials in PAH and CTEPH.


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