First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension

¹ Dept of Internal Medicine, University Hospital Giessen and Marburg, Giessen, Germany
² Clinical Pharmacology, Bayer HealthCare AG, Pharma Research Centre, 42096 Wuppertal, Germany
³ Global Biostatistics, Bayer HealthCare AG, Pharma Research Centre, 42096 Wuppertal, Germany

^* To whom correspondence should be addressed. E-mail: ardeschir.ghofrani{at}innere.med.uni-giessen.de.

	Abstract

Pulmonary hypertension (PH) is associated with impaired production of the vasodilator nitric oxide (NO). Riociguat (BAY 63-2521) acts directly on soluble guanylate cyclase, stimulating the enzyme and increasing sensitivity to low NO levels. This study evaluates riociguat safety, tolerability and efficacy in patients with moderate-to-severe PH (pulmonary arterial hypertension, distal chronic thromboembolic PH or PH with mild-to-moderate interstitial lung disease).

The optimal tolerated dose was identified by incremental dosing in four patients with PH; pharmacodynamic and pharmacokinetic parameters were assessed following single dose administration (2.5 mg or 1 mg) in ten and five patients with PH respectively. All subjects were analysed for safety and tolerability (n=19).

Riociguat had a favourable safety profile at single doses 2.5 mg. It significantly improved pulmonary haemodynamic parameters and cardiac index in patients with PH in a dose-dependent manner, to a greater extent than inhaled NO. Although riociguat also had significant systemic effects and showed no pulmonary selectivity, mean systolic blood pressure remained >110 mmHg.

This is the first report describing the use of riociguat in patients with PH. The drug was well-tolerated and superior to NO in efficacy and duration. Riociguat therefore has potential as a novel therapy for PH, and warrants further investigation.

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