Clinical Trial

. 2025 Oct;42(10):5104-5123.

doi: 10.1007/s12325-025-03297-2. Epub 2025 Aug 11.

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

Olivier Sitbon¹, Sandeep Sahay², Pilar Escribano Subías³, Ronald L Zolty⁴, John F Kingrey⁵, John J Ryan⁶, Irina Sobol⁷, Namita Sood⁸, Raymond L Benza⁹, Richard N Channick¹⁰, Kelly M Chin¹¹, Robert P Frantz¹², Hossein-Ardeschir Ghofrani^{13

14}, Anna R Hemnes¹⁵, Vallerie V McLaughlin¹⁶, Jean-Luc Vachiéry¹⁷, Roham T Zamanian¹⁸, Anna Ter Veer¹⁹, Robert F Roscigno¹⁹, David Mottola¹⁹, Ed Parsley¹⁹, Richard Aranda¹⁹, Lawrence S Zisman¹⁹, Luke S Howard²⁰; TORREY Study Investigators

Affiliations

¹ Centre de Référence de l'Hypertension Pulmonaire (Réseau PulmoTension) Service de Pneumologie et Soins Intensifs Respiratoires, Université Paris-Saclay/Hôpital Bicêtre, 78, rue Général Leclerc, 94270, Le Kremlin-Bicêtre, France. olivier.sitbon@aphp.fr.
² Houston Methodist Hospital/Weill Cornell Medicine, Houston, TX, USA.
³ University Hospital 12 de Octubre, CIBER CV, Complutense University, Madrid, Spain.
⁴ University of Nebraska Medical Center, Omaha, NE, USA.
⁵ INTEGRIS Health Pulmonary Hypertension Center of Oklahoma, Oklahoma City, OK, USA.
⁶ University of Utah Health, Salt Lake City, UT, USA.
⁷ New York Presbyterian/Weill Cornell Medical Center, New York, NY, USA.
⁸ University of California Davis Medical Center, Sacramento, CA, USA.
⁹ Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁰ UCLA Medical Center, Los Angeles, CA, USA.
¹¹ UT Southwestern Medical Center, Dallas, TX, USA.
¹² Mayo Clinic, Rochester, MN, USA.
¹³ Universities of Giessen and Marburg Lung Center (UGMLC), Institute for Lung Health (ILH), Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Giessen, Germany.
¹⁴ Department of Medicine, Imperial College London, London, UK.
¹⁵ Vanderbilt University, Nashville, TN, USA.
¹⁶ University of Michigan, Ann Arbor, MI, USA.
¹⁷ Université Libre de Bruxelles, HUB - Hôpital Erasme, Brussels, Belgium.
¹⁸ Stanford University School of Medicine, Stanford, CA, USA.
¹⁹ Gossamer Bio, Inc., San Diego, CA, USA.
²⁰ Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.

PMID: 40788460
PMCID: PMC12474731
DOI: 10.1007/s12325-025-03297-2

Clinical Trial

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

Olivier Sitbon et al. Adv Ther. 2025 Oct.

. 2025 Oct;42(10):5104-5123.

doi: 10.1007/s12325-025-03297-2. Epub 2025 Aug 11.

Authors

Affiliations

¹ Centre de Référence de l'Hypertension Pulmonaire (Réseau PulmoTension) Service de Pneumologie et Soins Intensifs Respiratoires, Université Paris-Saclay/Hôpital Bicêtre, 78, rue Général Leclerc, 94270, Le Kremlin-Bicêtre, France. olivier.sitbon@aphp.fr.
² Houston Methodist Hospital/Weill Cornell Medicine, Houston, TX, USA.
³ University Hospital 12 de Octubre, CIBER CV, Complutense University, Madrid, Spain.
⁴ University of Nebraska Medical Center, Omaha, NE, USA.
⁵ INTEGRIS Health Pulmonary Hypertension Center of Oklahoma, Oklahoma City, OK, USA.
⁶ University of Utah Health, Salt Lake City, UT, USA.
⁷ New York Presbyterian/Weill Cornell Medical Center, New York, NY, USA.
⁸ University of California Davis Medical Center, Sacramento, CA, USA.
⁹ Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁰ UCLA Medical Center, Los Angeles, CA, USA.
¹¹ UT Southwestern Medical Center, Dallas, TX, USA.
¹² Mayo Clinic, Rochester, MN, USA.
¹³ Universities of Giessen and Marburg Lung Center (UGMLC), Institute for Lung Health (ILH), Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Giessen, Germany.
¹⁴ Department of Medicine, Imperial College London, London, UK.
¹⁵ Vanderbilt University, Nashville, TN, USA.
¹⁶ University of Michigan, Ann Arbor, MI, USA.
¹⁷ Université Libre de Bruxelles, HUB - Hôpital Erasme, Brussels, Belgium.
¹⁸ Stanford University School of Medicine, Stanford, CA, USA.
¹⁹ Gossamer Bio, Inc., San Diego, CA, USA.
²⁰ Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.

PMID: 40788460
PMCID: PMC12474731
DOI: 10.1007/s12325-025-03297-2

Abstract

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.

Keywords: Efficacy; Inhaled tyrosine kinase inhibitor; Long-term; PDGFR inhibitor; Pulmonary arterial hypertension; Pulmonary vascular resistance; Safety; Seralutinib.

Plain language summary

Pulmonary arterial hypertension is a progressive disease that causes small blood vessels in the lungs to get thicker and stiffer, making it harder for the heart to pump blood to the lungs. The phase 2 TORREY study compared inhaled seralutinib to placebo in 86 participants, showing that seralutinib reduced the pressure in blood vessels in the lungs better than placebo. This result was enhanced in participants with more severe symptoms. Seralutinib also made it easier to perform everyday activities, like walking, in patients with more symptoms. Mild-to-moderate cough was a common side effect, occurring with similar frequency in seralutinib and placebo treatment groups. In this article, we report results of an ongoing open-label extension study in which 74 patients (who participated in the TORREY study or an earlier study, collectively called the “parent studies”) received seralutinib for an extended period of time. The open-label extension looked at side effects as well as measures of improvement such as pressure in blood vessels in the lung and exercise capacity (using the 6-min walk test). Seralutinib was well tolerated. Ongoing improvements in lung blood vessel pressure and exercise capacity were observed. Because of these findings, a larger phase 3 study (PROSERA, NCT05934526) is currently underway.

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Conflict of interest statement

Declarations. Conflict of Interest: Olivier Sitbon reports having received grants or contracts for research and education (payment made to the institution) from Janssen, MSD, and Ferrer; received grants or contracts for education (payment made to the institution) from AOP Orphan; payment or honoraria for lectures from AOP Orphan and Ferrer; and for educational events, lecturer, from Janssen and MSD; support for attending meetings or travel (travel costs) from MSD and Janssen; and participated on an Advisory Committee for Gossamer Bio, Inc., AOP Orphan, Enzyvant, Ferrer, Janssen, Liquidia, Roivant, MSD, and United Therapeutics. Sandeep Sahay reports having received consulting fees from Janssen, United Therapeutics, Liquidia, Keros, and Merck; support for attending meetings and/or travel from Janssen for presenting scientific work at WSPH meeting; patents submitted for Janssen as inventor, secondary titration of Uptravi; participation on an advisory board for United Therapeutics, Bayer, Liquidia, Merck, and Gossamer Bio, Inc.; participation as Chair and member of a Data Safety Monitoring Board for NIH-funded trials; holding a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as PVD section Chair, ACCP, CHEST, Member of scientific leadership committee PHA. Pilar Escribano Subías reports having received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Janssen, MSD, Ferrer, AOT, and Aerovate; support for attending meetings and/or travel from Janssen and MSD; participation on a data safety monitoring board or advisory board for Gossamer Bio, Inc., Janssen, MSD, AOT, Aerovate, and Ferrer; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Gossamer Bio, Inc. Ronald L. Zolty reports having received consulting fees from Johnson & Johnson, United Therapeutics, Bayer, and Alnylam. John J. Ryan reports having received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Bayer, Merck, Janssen PH, United Therapeutics, and Liquidia. Namita Sood reports having received consulting fees from United Therapeutics and Merck; membership in a Speakers Bureau for Bayer and BI; and membership in an Advisory Board for United Therapeutics and Merck. Raymond L. Benza reports having received consulting fees from Merck, United Therapeutics, KEROS, Aerovate, Insmed, and Cereno; served as an advisory committee member for Gossamer Bio, Inc.; served as an advisory board member for Altavant, Merck, Janssen, and Insmed; served on a data safety monitoring board for Janssen; and served on a scientific advisory board for Cereno. Richard N. Channick reports having received consulting fees from Gossamer Bio, Inc., Janssen, Bayer, United Therapeutics, and Third Pole; payment or honoraria for lectures from Janssen and Bayer; and participated on an advisory committee for Gossamer Bio, Inc., Janssen, and Bayer. Kelly M. Chin reports having received grants or contracts (fees to institution) for clinical studies overseen by her from Gossamer Bio, Inc., Janssen, United Therapeutics, Merck, and Altavant; received fees for work on an advisory board for Merck; received fees for work as an advisory committee member for Gossamer Bio, Inc.; received fees for work as a steering committee member for Janssen; received fees for work on an adjudication committee for United Therapeutics; and received fees for an editorial role with the American Heart Association. Robert P. Frantz reports having royalties or licenses from UpToDate; receiving consulting fees from Janssen and Liquidia; participated on a Data Safety Monitoring board for Aerovate; participated as an Advisory Committee member for Gossamer Bio, Inc.; participated on an Advisory Board for Janssen, Liquidia, Tenax Therapeutics, ShouTi, Insmed, and Merck. Hossein-Ardeschir Ghofrani reports having received consulting fees from Gossamer Bio, Inc., Aerovate, Altavant, Bayer AG, Attgeno, Janssen/Actelion, MSD/Acceleron, and Pfizer; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events as a speaker from Bayer AG, Janssen/Actelion, and MSD/Acceleron; participated as an Advisory Committee member for Aerovate, Altavant, Bayer AG, Attgeno, Janssen/Acctelion, MSD/Acceleron, and Pfizer; and as a member of a Data and Safety Monitoring Board for Insmed. Anna R. Hemnes reports having received grants or contracts from NHLBI; consulting fees from United Therapeutics, Tenax Therapeutics, Merck, and Janssen; having served as an Advisory Committee member for Gossamer Bio, Inc.; and having held stock from Tenax Therapeutics. Vallerie V. McLaughlin reports having received grant support from Aerovate, Enzyvant/Altavant, Gossamer Bio, Inc., Janssen, Merck/Acceleron, Sonovie, and Keros; consulting fees from Aerami, Aerovate, Altavant, Apollo, Bayer, CVS/Caremark, LLC, Corvista, Gossamer Bio, Inc., Janssen, Keros, Liquidia, Merck, Morphic, Regeneron, Respira, Roivant, United Therapeutics, and Vertex; and participated as an advisory committee member for Gossamer Bio, Inc. Jean-Luc Vachiéry reports having received consulting fees from Gossamer Bio, Inc., Insmed, and Tectonic; and consulting fees paid to his institution from Aerovate, Janssen, Enzyvant, Bayer HealthCare, Merck, Liquidia, and Aerami; received payment or honoraria (payment to institution) for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen, Merck, Novartis, and Boehringer Ingelheim; received payment for expert testimony from Actelion Pharmaceuticals; received either support for attending meetings or travel (payment to institution) from Merck; participated on a data safety monitoring board (payment to institution) from Janssen, GSK, and Moderna; membership on Steering Committees for Gossamer Bio, Inc., Insmed, Merck, and United Therapeutics. Roham T. Zamanian reports having received grants or contracts for industry-supported research from United Therapeutics, Janssen, Tenax Therapeutics, and Gossamer Bio, Inc.; consulting fees from Janssen, Vivus, Morphogen-IX, Merck, and Gossamer Bio, Inc.; and stock or stock options from Selten. Luke S. Howard reports having received payment or honoraria for speaker bureau membership from Janssen; participated as an Advisory Board member for Janssen, MSD, Altavant, United Therapeutics, Keros Therapeutics, and Liquidia, and as an Advisory Committee member for Gossamer Bio, Inc.; and having stock or stock options (shareholder) at ATXA Therapeutics, iOWNA, Circular, and Calibre Biometrics. Anna ter Veer, Robert F. Roscigno, David Mottola, Ed Parsley, Richard Aranda, and Lawrence S. Zisman, report stocks or stock options from Gossamer Bio, Inc.; and employment at Gossamer Bio, Inc. Lawrence S. Zisman also reports patents related to seralutinib (assigned to Gossamer Bio, Inc., or Pulmokine) and other financial or non-financial interests (payments) from Xoma, Inc. Olivier Sitbon, Pilar Escribano Subías, Ronald L. Zolty, John F. Kingrey, John J. Ryan, Irina Sobol, Namita Sood, Raymond L. Benza, Richard N. Channick, Kelly M. Chin, Robert P. Frantz, Hossein-Ardeschir Ghofrani, Anna R. Hemnes, Vallerie V. McLaughlin, Jean-Luc Vachiéry, Roham T. Zamanian, and Luke S. Howard, report receiving medical writing and editing support, and rapid service fee support, for the present manuscript funded by Gossamer Bio, Inc. and Open Access fee support from the Université Paris-Saclay. Ethical Approval: The OLE protocol and all study-related documents were approved at each study center by the institutional review board or independent ethics committee for each site (Supplementary material). The OLE study was conducted in accordance with the tenets of the Declaration of Helsinki and the International Conference on Harmonisation-Good Clinical Practice, and all applicable laws and regulations. Prior to participation, all patients provided written informed consent.

Figures

**Fig. 1**
Open-label study design for patients who completed prior seralutinib studies. *BID* twice daily, *OLE* open-label extension, *RHC* right heart catheterization

**Fig. 2**
Patient disposition in TORREY and TORREY open-label studies (as of December 5, 2024). Eighty-six patients were randomized in TORREY and 8 patients were randomized in the phase 1b trial. *ALT* alanine aminotransferase, *BID* twice daily, *OLE* open-label extension. ^aAdverse events leading to treatment discontinuation were cough (5), ALT increased (1), abdominal pain (1), acute respiratory failure (1), arthralgia (1), confusional state (1), respiratory failure (1), pulmonary arterial hypertension (1), and throat irritation (1). ^bAdverse events leading to treatment discontinuation were cough (4), vomiting (1), ALT increased (1), and vascular device infection (1)

**Fig. 3**
PVR in the OLE study (safety population). A Median (IQR) change in PVR (dyne·s/cm⁵) at weeks 24 and 72 from the double-blind period of TORREY (left) and the open-label extension (right). B Median (IQR) PVR (dyne·s/cm⁵) for patients in the Placebo Crossover group and Seralutinib Continued group at TORREY baseline, week 24, and week 72. C Percent change in PVR at weeks 24 and 72 (per individual patient) in patients with week 72 right heart catheterization data originally randomized to seralutinib or originally randomized to placebo. Open teal circles represent week 24 data for patients randomized to seralutinib in TORREY. Filled teal circles represent week 72 data for patients randomized to seralutinib in TORREY. Open gray circles represent week 24 data for patients randomized to placebo in TORREY. Filled gray circles represent week 72 data for patients randomized to placebo in TORREY. *IQR* interquartile range, *OLE* open-label extension, *PVR* pulmonary vascular resistance

**Fig. 4**
Mean change (SE) in 6MWD throughout the double-blind TORREY and OLE studies for Placebo Crossover and Seralutinib Continued groups (OLE safety population). Teal = seralutinib; gray = placebo. Number of patients evaluable at each visit are shown below the graph for each time point. *6MWD* 6-min walk distance, *OLE* open-label extension, SE standard error

**Fig. 5**
NT-proBNP throughout the double-blind TORREY and OLE studies (OLE safety population). Teal = seralutinib; gray = placebo. Number of patients evaluable at each visit are shown below the graph for each time point. Two very large outliers (13,022 ng/l; 14,520 ng/l) in the Placebo Crossover group are not shown at week 72. *NT-proBNP* N-terminal pro b-type natriuretic peptide, *OLE* open-label extension, SE standard error

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References

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

Affiliations

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

Authors

Affiliations

Abstract

Plain language summary

Conflict of interest statement

Figures

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