Circulating Biomarker Results from a Phase 2 Study of Seralutinib in Pulmonary Arterial Hypertension
ORCID
0000-0001-9627-6236 (Benza)
Document Type
Article
Publication Date
2026
DOI
10.1093/ajrccm/aamag175
Publication Title
American Journal of Respiratory and Critical Care Medicine
Volume
Advance online publication
Pages
23 pp.
Abstract
[Introduction] To the Editor: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by obstructive pulmonary arterial remodeling (1). Seralutinib, an investigational inhaled tyrosine kinase inhibitor, potently and selectively targets kinases relevant to PAH pathobiology including platelet-derived growth factor receptors (PDGFR) α and β, colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) (2). In preclinical models, seralutinib improved cardiopulmonary hemodynamics, reversed pulmonary vascular pathology and decreased right ventricular hypertrophy (3). In TORREY, a phase 2, multicenter, double-blind, randomized, placebo-controlled trial in PAH, seralutinib significantly reduced pulmonary vascular resistance (PVR) after 24 weeks with good tolerability (4). Interim analysis of an open-label extention (OLE) study showed further PVR reductions with seralutinib through 72 weeks (5). In this exploratory, hypothesis-generating biomarker analysis, we evaluated pharmacodynamic activity of seralutinib to identify circulating proteins associated with treatment and characterize the mechanism of action (MOA) in PAH patients. Some results were previously reported in abstract form (6,7).
Rights
© The Authors 2026.
Published by Oxford University Press on behalf of the American Thoracic Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) License, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints.
Original Publication Citation
Osterhout, R., Boucly, A., Benza, R. L., Channick, R. N., Chin, K. M., Frantz, R. P., Hemnes, A. R., Howard, L. S., McLaughlin, V. V., Sitbon, O., Vachiéry, J.-L., Zamanian, R. T., Aranda, R., Cravets, M., Ding, Z., Duong-Verlé, T., Mottola, D., Roscigno, R. F., Sitapara, R.,…Ghofrani, H.-A. (2026). Circulating biomarker results from a phase 2 study of seralutinib in pulmonary arterial hypertension. American Journal of Respiratory and Critical Care Medicine. Advance online publication. https://doi.org/10.1093/ajrccm/aamag175
Repository Citation
Osterhout, R., Boucly, A., Benza, R. L., Channick, R. N., Chin, K. M., Frantz, R. P., Hemnes, A. R., Howard, L. S., McLaughlin, V. V., Sitbon, O., Vachiéry, J.-L., Zamanian, R. T., Aranda, R., Cravets, M., Ding, Z., Duong-Verlé, T., Mottola, D., Roscigno, R. F., Sitapara, R.,…Ghofrani, H.-A. (2026). Circulating biomarker results from a phase 2 study of seralutinib in pulmonary arterial hypertension. American Journal of Respiratory and Critical Care Medicine. Advance online publication. https://doi.org/10.1093/ajrccm/aamag175
Supplementary Data
Included in
Cellular and Molecular Physiology Commons, Hematology Commons, Hemic and Immune Systems Commons, Molecular, Cellular, and Tissue Engineering Commons, Pharmaceutics and Drug Design Commons
Comments
Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the authors, article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout.