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Войти в исследования Advances in therapy · 2025
Seralutinib for the Treatment of Pulmonary Arterial Hypertension in Adults: TORREY Open-Label Extension Study.
СтатьяРандомизированное исследованиеКлиническое исследование II фазыМногоцентровое исследованиеКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
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Sitbon Olivier, Sahay Sandeep, Escribano Subías Pilar, Zolty Ronald L, Kingrey John F, Ryan John J, Sobol Irina, Sood Namita, Benza Raymond L, Channick Richard N, Chin Kelly M, Frantz Robert P, Ghofrani Hossein-Ardeschir, Hemnes Anna R, McLaughlin Vallerie V, Vachiéry Jean-Luc, Zamanian Roham T, Ter Veer Anna, Roscigno Robert F, Mottola David, Parsley Ed, Aranda Richard, Zisman Lawrence S, Howard Luke S, TORREY Study Investigators
Аннотация
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. A Graphical Abstract is available for this article.
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. A Graphical Abstract is available for this article.