EXPRESS: Riociguat improves health-related quality of life for patients with pulmonary arterial hypertension: results from the phase 4 MOTION study Running title: Riociguat improves HRQoL in phase 4 MOTION study.

Pulmonary arterial hypertension (PAH) is characterized by progressive dyspnea and exercise limitation and is associated with reduced health-related quality of life. Few clinical studies have evaluated the primary effects of treatment of PAH from the patient perspective. Here, we present the impact of riociguat on patient-reported outcomes (PROs) in treatment-naive patients with PAH. MOTION (NCT02191137) was an open-label, phase 4 trial of riociguat monotherapy in treatment-naive patients with PAH. The primary endpoint was the change in total score from baseline to Week 24 in the Living with Pulmonary Hypertension (LPH) questionnaire. The Short Form-12 Health Survey and Work Limitations Questionnaire 8 were also utilized to assess PROs. Other secondary endpoints included change from baseline in World Health Organization functional class (WHO FC), 6-min walk distance (6MWD), Modified Borg Dyspnea Scale, and safety. At week 24 (n = 66), the mean (standard deviation [SD]) total LPH score was 37.17 (24.61), for a mean (SD) change from baseline of -10.99 (22.51). At last visit, with week 24 imputed, the mean (SD) total score was 40.63 (28.38), for a mean (SD) change from baseline of -5.40 (27.8) (n = 75; P = 0.0484). Improvement in LPH questionnaire total score was observed by week 4 and was maintained through week 24. Improvements were observed in WHO FC, Modified Borg Dyspnea Scale, and accelerometer-measured 6MWD at week 24. Treatment with riociguat had a positive impact on PROs in treatment-naive patients with PAH and was well tolerated, with a similar safety profile to that observed in placebo-controlled phase 3 trials.