Riociguat for Pulmonary Hypertension

Abstract

Pulmonary hypertension (PH) encompasses a group of diseases associated with progressively increasing pulmonary vascular resistance, right heart failure and premature death. Riociguat is a novel, first-in-class oral drug that directly stimulates soluble guanylate cyclase, both independently of the endogenous vasodilator nitric oxide (NO) and in synergy with NO. Single oral doses of riociguat were well tolerated in a Phase I study of healthy volunteers. They had a favorable safety profile, and improved pulmonary hemodynamics and cardiac index to a greater extent than inhaled NO in a proof-of-concept study in patients with moderate-to-severe PH. In a 12-week Phase II trial in patients with chronic thromboembolic PH or pulmonary arterial hypertension, pulmonary hemodynamics and exercise capacity improved following individual dose titration with oral riociguat, which was generally well tolerated. Further trials in PH have been initiated.

Keywords:

• chronic thromboembolic pulmonary hypertension
• pulmonary arterial hypertension
• pulmonary hypertension
• riociguat
• soluble guanylate cyclase

Financial & competing interests disclosure

Hossein-Ardeschir Ghofrani has received honoraria and research funds from Actelion, Bayer Schering, ErgoNex Pharma, GlaxoSmithKline, Novartis and Pfizer. Robert Voswinckel has received honoraria from Actelion, BayerSchering and Pfizer. Henning Gall has received honoraria from Actelion and BayerSchering. Norbert Weissmann has received research funds from ErgoNex Pharma, BayerSchering, Solvay and Pfizer. Ralph T Schermuly has received research funds from Actelion, ErgoNex Pharma, Bayer Schering, Solvay and Pfizer. Friedrich Grimminger has received hono- raria and research funds from Actelion, Bayer Schering,Novartis and Pfizer. Werner Seeger has received honoraria and research funds from Actelion, BayerSchering and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. Dr Anja Becher from Oxford PharmaGenesis Ltd (Oxford, UK) provided editorial assistance, supported by Bayer Schering Pharma AG, Germany.