Riociguat (BAY-63-2521) is an oral soluble guanylate cyclase stimulator in phase III clinical development at Bayer Schering Pharma for the treatment of chronic thromboembolic pulmonary hypertension and for the treatment of pulmonary arterial hypertension (PAH). The compound stimulates sGC, which leads to the catalyzing of cyclic guanosine monophosphate (cGMP), resulting in the dilation of blood vessels, lowering of blood pressure and the mediation of tissue-protective effects.

In February, Bayer Schering Pharma initiated two phase III clinical trials of riociguat: CHEST-1 (chronic thromboembolic pulmonary hypertension sGC stimulator trial) and PATENT-1 (pulmonary arterial hypertension sGC stimulator trial). CHEST-1 is a multicenter, double-blind, randomized, placebo-controlled trial in patients with inoperable chronic thromboembolic pulmonary hypertension. The trial will involve 270 patients who will be randomized to receive either riociguat or placebo for 16 weeks. The treatment success will be measured as the change from baseline in patients' exercise capacity, using the six-minute walking distance test. After the 16-week treatment in CHEST-1, all patients will have the opportunity to participate in an open-label, long-term study (CHEST-2) during which longer-duration safety and efficacy aspects will be assessed. PATENT-1 is a multicenter, double-blind, randomized, placebo-controlled trial in patients with pulmonary arterial hypertension who are either treatment-naive or are being treated with an endothelin receptor antagonist or a prostacyclin analogue. The trial will involve 460 patients who will be randomized to receive either riociguat or placebo. The primary endpoint will be the change from baseline in the six-minute walking distance test after 12 weeks of treatment with riociguat compared to the change in the placebo group. After this study, all patients will have the opportunity to participate in an open-label, long-term study (PATENT-2) during which longer-duration safety and efficacy aspects will be assessed. First results from both trials are expected in 2011.

In 2007, orphan drug designation was received in the E.U. for the treatment of pulmonary arterial hypertension, including treatment of chronic thromboembolic pulmonary hypertension.