Riociguat is a soluble guanylate cyclase (sGC) stimulator which has a dual mechanism of action. It sensitises sGC to endogenous nitric oxide (NO) by stabilising binding between sGC and NO and directly stimulates sGC independently of NO.
Riociguat has been studied in two key phase III clinical trials. The PATENT-1 study evaluated riociguat in patients with symptomatic pulmonary arterial hypertension and the CHEST-1 study assessed the efficacy and safety of riociguat for the treatment of chronic thromboembolic pulmonary hypertension that was inoperable or that had persisted or recurred after pulmonary endartectomy.
In both trials, patients were randomised to receive placebo or riociguat titrated over 8 weeks to optimal individual dose (range 500 microgram to 2.5mg three times daily), which was then maintained over a further 4 weeks in PATENT-1 and 8 weeks in CHEST-1.
The primary endpoint, placebo-adjusted change from baseline in 6-minute walk distance, was 36 metres in PATENT-1 and 46 metres in CHEST-1 (p<0.0001 for both comparisons).
Headache, hypotension, GI upset, dizziness and peripheral oedema were the most commonly reported adverse effects.
Further information: Bayer