Sustained benefit with seralutinib treatment: Lessons from the open-label extension (OLE) of the TORREY study

Objective: A reduction in pulmonary vascular resistance (PVR) of 15-50% in patients with pulmonary arterial hypertension (PAH) has been observed in studies of combination therapy. Seralutinib, a novel inhaled PDGFRα/β, CSF1R, and c-KIT kinase inhibitor, significantly reduced PVR at Week (W) 24 in the phase 2 TORREY study ( NCT04456998 ). Most patients were WHO functional class (FC) II, receiving 3 PAH medications at randomization (baseline, BL), including prostacyclin. To characterize the longer-term hemodynamic benefits of seralutinib, we identified patients in the OLE ( NCT04816604 ) with a > 15% reduction in PVR from BL to W72. Methods: 74 patients enrolled in the OLE. Hemodynamic data were available for 53 patients at W72; patients demonstrating a > 15% PVR reduction from BL to W72 were identified. Results are descriptive. Results: Seralutinib treatment for up to 72 weeks resulted in a > 15% PVR decrease in 26 (49%) patients. The mean BL PVR was 643 dynes*s/cm5, six-minute walk distance (6MWD) was 413 m, and 17 patients were WHO FC II. 13 patients were receiving 3 PAH medications, including prostacyclin. The mean PVR reduction was 234 dynes*s/cm5 (36%) at W72. Furthermore, mean pulmonary artery pressure decreased by 6.5 mmHg (13%), cardiac output increased by 0.9 L/min (20%), and 6MWD increased from BL by 40 m. Seralutinib was well tolerated. Conclusions: In 49% of patients with W72 right heart catheterization data, longer-term seralutinib treatment resulted in sustained hemodynamic and 6MWD improvement.