Seralutinib for the Treatment of Pulmonary Arterial Hypertension in Adults: TORREY Open-Label Extension Study

Introduction: Seralutinib is an inhaled tyrosine kinase inhibitor targeting platelet-derived growth factor receptor (PDGFR) α/β, colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) kinases. TORREY, a phase 2, double-blind, randomized, placebo-controlled study of seralutinib in pulmonary arterial hypertension (PAH), met its primary endpoint, demonstrating a significant reduction in pulmonary vascular resistance (PVR) over placebo after 24 weeks (NCT04456998; EudraCT 2019-002669-37). We present results (as of December 5, 2024) from an open-label extension (OLE) study evaluating long-term safety, tolerability, and efficacy of seralutinib in adults with PAH (NCT04816604). Methods: Seventy-three of 80 patients who completed TORREY (WHO Group 1 PH on stable PAH medications) and 1/8 patients from a phase 1b study (NCT03926793) enrolled in the OLE. The study design called for dosing of inhaled seralutinib 90 mg twice daily. Treatment-emergent adverse events (TEAEs) were monitored. PVR was measured after 48 weeks (week 72 from TORREY baseline). Analyses are descriptive. Results: At OLE entry, 34 patients continued on seralutinib (Seralutinib Continued); 40 switched from placebo to seralutinib (Placebo Crossover). Common TEAEs were headache (28.4%), coronavirus disease (COVID-19) (27.0%), and cough (23.0%). TEAEs led to seralutinib discontinuation in 20 (27.0%) patients; cough was the reason in 9/74 (12.2%). In the Seralutinib Continued group, median change in PVR from TORREY baseline to weeks 24 and 72 was − 94 dyne·s/cm⁵ and − 143 dyne·s/cm⁵, respectively (n = 28). In the Placebo Crossover group, corresponding values were − 32 dyne·s/cm⁵ and − 56 dyne·s/cm⁵, respectively (n = 27). Continued improvement in 6-min walk distance was observed. N-terminal pro-brain natriuretic peptide (NT-proBNP) significantly decreased with seralutinib during TORREY and remained stable throughout the OLE. After an increase in TORREY, NT-proBNP levels in the Placebo Crossover group nearly returned to TORREY baseline at week 72. Conclusions: These OLE data are consistent with TORREY results and support long-term safety and efficacy of inhaled seralutinib in patients with PAH. A phase 3 study of seralutinib in PAH is underway (PROSERA, NCT05934526). Clinical Trial Registration: ClinicalTrials.gov identifier NCT04816604.