Riociguat ( Adempas ) is a soluble guanylate cyclase stimulator approved for the treatment of inoperable and persistent / recurrent chronic thromboembolic pulmonary hypertension ( CTEPH ).
In the 16-week CHEST-1 study, Riociguat showed a favourable benefit-risk profile and improved several clinically relevant end-points in patients with chronic thromboembolic pulmonary hypertension.
The CHEST-2 open-label extension evaluated the long-term safety and efficacy of Riociguat. Eligible patients from CHEST-1 received Riociguat individually adjusted up to a maximum dose of 2.5 mg three-times daily.
The primary objective was the safety and tolerability of Riociguat; exploratory efficacy end-points included 6-min walking distance ( 6MWD ) and World Health Organization ( WHO ) functional class ( FC ).
Overall, 237 patients entered CHEST-2 and 211 ( 89% ) were ongoing at this interim analysis ( March 2013 ).
The safety profile of Riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals.
Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to 1 year in CHEST-2. In the observed population at 1 year, mean±sd 6MWD had changed by +51±62 m ( n=172 ) versus CHEST-1 baseline ( n=237 ), and WHO FC had improved / stabilised / worsened in 47/50/3% of patients ( n=176 ) versus CHEST-1 baseline ( n=236 ).
Long-term Riociguat had a favourable benefit-risk profile and apparently showed sustained benefits in exercise and functional capacity for up to 1 year. ( Xagena )
Simonneau G et al, Eur Respir J 2014; Epub ahead of print