Riociguat for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH): Final data from a phase II long-term extension (LTE) study

Background: Riociguat was well tolerated and significantly improved 6MWD and WHO FC in a Phase II study of pts with PAH or CTEPH. We present final safety and efficacy data from the LTE phase of this study. Methods: Pts with PAH or CTEPH completing the initial 12-wk trial were eligible to enter the LTE. All pts received riociguat individually adjusted to a maximum dose of 2.5 mg three-times daily (tid). The primary outcome was safety and tolerability; secondary outcomes included change from baseline in 6MWD and WHO FC. Results: Of 72 pts in the initial study, 68 (94%) entered the LTE. At study completion, median treatment duration was 77 months (range 3–87 months). Thirty-six (53%) pts remained in the LTE until completion and 32 (47%) discontinued treatment; 11 (16%) due to death (all judged unrelated to study drug) and 6 (9%) due to adverse events (AEs). AEs and serious AEs were reported by 63 (93%) and 52 (76%) pts, respectively. Nasopharyngitis (57%) and peripheral edema (37%; 3% drug-related) were the most common AEs. Mean±SD 6MWD increased from baseline by 58±104 m (n=36) in the overall population at Month 72, and by 87±121 m (n=13) and 41±91 m (n=23) in pts with PAH and CTEPH, respectively. At Month 72, WHO FC had improved/stabilized/worsened vs baseline in 51/43/5% of the overall population (n=37), 62/38/0% of PAH pts (n=13), and 46/46/8% of CTEPH pts (n=24). Survival in the overall population at approximately 9, 36, and 72 months was 97, 91, and 81%, respectively. Conclusions: Riociguat is generally well tolerated in pts with PAH and CTEPH, and led to sustained improvements in 6MWD and WHO FC for up to 6 years.