Riociguat for the Treatment of Pulmonary Arterial Hypertension (PAH): 1-Year Results from the PATENT-2 Long-term Extension Study

Abstract

PURPOSE: In the 12‐week PATENT‐1 study, riociguat, a novel soluble guanylate cyclase stimulator, significantly improved 6‐minute walking distance (6MWD) and several secondary endpoints in PAH patients. These improvements were maintained for a further 12 weeks in the PATENT‐2 long‐term extension study. Here we present 1‐year data from PATENT‐2. METHODS: Patients could enter PATENT‐2 after successful completion of PATENT‐1 without experiencing ongoing riociguat‐related serious adverse events. During the initial 8‐week blinded period of PATENT‐2, riociguat individual‐titration arm patients continued on their optimum dose (up to 2.5 mg tid) while receiving sham titration; placebo and capped‐dose (up to 1.5 mg tid) arm patients were titrated to their optimum dose (up to 2.5 mg tid). The primary endpoints were safety and tolerability; secondary endpoints included 6MWD and WHO functional class (FC). RESULTS: Of 443 patients in PATENT‐1, 396 (89%) entered PATENT‐2. In this interim analysis (cut‐off March 2013), 324 (82%) patients were ongoing, and 334 (84%) had received ≥1 year of treatment. Overall, 8% of patients withdrew due to adverse events. Long‐term riociguat was well tolerated, with no new safety signals. At the end of PATENT‐1, 6MWD increased by 37±52 m (mean±SD) in the individual‐titration arm, 46±51 m in the capped‐dose arm, and 12±58 m in the placebo arm of the cohort entering PATENT‐2. After 1 year of PATENT‐2 (overall cohort; n=327), 6MWD increased by 51±74 m versus PATENT‐1 baseline. At the end of PATENT‐1, FC was improved/stable/worsened in 21/78/2%, 25/69/5%, and 16/74/9% (data missing for n=1) of individual‐titration, capped‐dose, and placebo‐arm patients, respectively. After 1 year (overall cohort; n=339), the proportions were 33/61/6%. Sixty‐one (15%) patients included in the safety and efficacy analyses received additional PAH medication during PATENT‐2 (n=60 due to worsening pulmonary hypertension). CONCLUSIONS: Long‐term riociguat is well tolerated in PAH patients and shows sustained benefits in 6MWD and FC when used as a monotherapy or in combination with concomitant PAH therapies.