Clinical Trial

. 2025 Nov:248:108318.

doi: 10.1016/j.rmed.2025.108318. Epub 2025 Aug 27.

BREEZE Optional Extension Phase: Long-term safety and efficacy of treprostinil dry powder inhaler (Tyvaso DPI) in pulmonary arterial hypertension

Sandeep Sahay¹, Harold Palevsky², Karim El-Kersh³, Ricardo Restrepo-Jaramillo⁴, Abubakr A Bajwa⁵, Sapna Desai⁶, Joanna M Joly⁷, Leslie A Spikes⁸, Michael S Eggert⁹, Shilpa Johri¹⁰, Shelley M Shapiro¹¹, Micah R Fisher¹², Trushil G Shah¹³, Gautam V Ramani¹⁴, Jinesh P Mehta¹⁵, Claire M Thrasher¹⁶, Chunqin Deng¹⁶, Peter Smith¹⁶, Meredith Broderick¹⁶, Charles D Burger¹⁷

Affiliations

¹ Division of Pulmonary, Critical Care and Sleep Medicine, Houston Methodist Hospital, 6445 Main St, Houston, TX, 77030, USA.
² Perelman School of Medicine of the University of Pennsylvania, Penn Presbyterian Medical Center, 3737 Market St, Philadelphia, PA, 19104, USA.
³ Department of Medicine, Division of Pulmonary Critical Care and Sleep Medicine, University of Arizona College of Medicine, 1111 East McDowell Rd, Phoenix, AZ, 85006, USA.
⁴ University of South Florida, 2 Tampa General Cir, Tampa, FL, 33606, USA.
⁵ Mayo Clinic College of Medicine & Science, Department of Pulmonary, Allergy & Sleep Medicine Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA.
⁶ John Ochsner Heart and Vascular Institute, Ochsner Medical Center, 1514 Jefferson Hwy, New Orleans, LA, 70121, USA.
⁷ Division of Cardiovascular Disease, UAB Department of Medicine, 500 22nd St S, Birmingham, AL, 35233, USA.
⁸ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA.
⁹ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Sentara Cardiovascular Research Institute, 600 Gresham Dr, Norfolk, VA, 23507, USA.
¹⁰ Pulmonary and Critical Care Medicine, Pulmonary Associates of Richmond Inc, 6600 W Broad St, Richmond, VA, 23230, USA.
¹¹ Division of Cardiology, VA Greater Los Angeles Healthcare System, Division of Pulmonary Critical Care, David Geffen UCLA School of Medicine, 200 Medical Plaza, Los Angeles, CA, 90095, USA.
¹² Emory University Division of Pulmonary Allergy, Critical Care and Sleep Medicine, 1365 Clifton Rd NE, Atlanta, GA, 30322, USA.
¹³ Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine University of Texas Southwestern Medical Center, 5939 Harry Hines Blvd, Dallas, TX, 75390, USA.
¹⁴ Division of Cardiology, University of Maryland, 419 West Redwood St, Baltimore, MD, 21201, USA.
¹⁵ Pulmonary and Critical Care Medicine, The Cleveland Clinic, 2950 Cleveland Clinic Blvd, Weston, FL, 33331, USA.
¹⁶ United Therapeutics Corporation, 55 T.W. Alexander Dr, Durham, NC, 27709, USA.
¹⁷ Department of Pulmonary and Critical Care Medicine, Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA. Electronic address: burger.charles@mayo.edu.

PMID: 40882760
DOI: 10.1016/j.rmed.2025.108318

Free article

Clinical Trial

BREEZE Optional Extension Phase: Long-term safety and efficacy of treprostinil dry powder inhaler (Tyvaso DPI) in pulmonary arterial hypertension

Sandeep Sahay et al. Respir Med. 2025 Nov.

Free article

. 2025 Nov:248:108318.

doi: 10.1016/j.rmed.2025.108318. Epub 2025 Aug 27.

Authors

Affiliations

¹ Division of Pulmonary, Critical Care and Sleep Medicine, Houston Methodist Hospital, 6445 Main St, Houston, TX, 77030, USA.
² Perelman School of Medicine of the University of Pennsylvania, Penn Presbyterian Medical Center, 3737 Market St, Philadelphia, PA, 19104, USA.
³ Department of Medicine, Division of Pulmonary Critical Care and Sleep Medicine, University of Arizona College of Medicine, 1111 East McDowell Rd, Phoenix, AZ, 85006, USA.
⁴ University of South Florida, 2 Tampa General Cir, Tampa, FL, 33606, USA.
⁵ Mayo Clinic College of Medicine & Science, Department of Pulmonary, Allergy & Sleep Medicine Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA.
⁶ John Ochsner Heart and Vascular Institute, Ochsner Medical Center, 1514 Jefferson Hwy, New Orleans, LA, 70121, USA.
⁷ Division of Cardiovascular Disease, UAB Department of Medicine, 500 22nd St S, Birmingham, AL, 35233, USA.
⁸ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA.
⁹ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Sentara Cardiovascular Research Institute, 600 Gresham Dr, Norfolk, VA, 23507, USA.
¹⁰ Pulmonary and Critical Care Medicine, Pulmonary Associates of Richmond Inc, 6600 W Broad St, Richmond, VA, 23230, USA.
¹¹ Division of Cardiology, VA Greater Los Angeles Healthcare System, Division of Pulmonary Critical Care, David Geffen UCLA School of Medicine, 200 Medical Plaza, Los Angeles, CA, 90095, USA.
¹² Emory University Division of Pulmonary Allergy, Critical Care and Sleep Medicine, 1365 Clifton Rd NE, Atlanta, GA, 30322, USA.
¹³ Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine University of Texas Southwestern Medical Center, 5939 Harry Hines Blvd, Dallas, TX, 75390, USA.
¹⁴ Division of Cardiology, University of Maryland, 419 West Redwood St, Baltimore, MD, 21201, USA.
¹⁵ Pulmonary and Critical Care Medicine, The Cleveland Clinic, 2950 Cleveland Clinic Blvd, Weston, FL, 33331, USA.
¹⁶ United Therapeutics Corporation, 55 T.W. Alexander Dr, Durham, NC, 27709, USA.
¹⁷ Department of Pulmonary and Critical Care Medicine, Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA. Electronic address: burger.charles@mayo.edu.

PMID: 40882760
DOI: 10.1016/j.rmed.2025.108318

Abstract

Introduction: Pulmonary arterial hypertension (PAH) is a rare and progressive disease associated with significant morbidity and mortality. Prostacyclins, including treprostinil, are a mainstay of PAH treatment, particularly in patients with intermediate to high risk of death. Following the approval of treprostinil inhalation solution for PAH, treprostinil dry powder inhaler (DPI) was developed as a small, portable, low-maintenance device to improve patient experience.

Objective: The primary objective of the BREEZE study was to assess the safety and tolerability of treprostinil DPI in PAH.

Methods: BREEZE was a 3-week, single-arm, open-label study in which patients with PAH transitioned from a stable dose of treprostinil inhalation solution to a comparable dose of treprostinil DPI.

Results: Following the 3-week treatment phase, 49 of 51 patients opted to enroll in the Optional Extension Phase (OEP). Throughout the OEP, 6MWD continued to increase with a median change from baseline of 16 m at week 107 and over a third of patients experiencing an improvement of at least 30 m. Patient satisfaction with the DPI device was overwhelmingly positive while drug-related adverse events were infrequent and characteristic of prostacyclin therapy.

Conclusion: The BREEZE OEP successfully demonstrated the safety of long-term treatment with treprostinil DPI in patients with PAH.

Clinical trial registration: NCT03950739.

Keywords: Dry powder inhaler; Exercise capacity; Prostacyclin dosing; Pulmonary arterial hypertension; Treprostinil.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:CB has received grants or consulting fees from Merck, Insmed, Gossamer Bio, Liquidia, Aerovate, and Janssen. KEK has received consulting fees from and participated in Advisory Boards for United Therapeutics, Johnson and Johnson, and Merck. SJ has received consulting fees from United Therapeutics, Bellerophon, Bayer, and Acceleron, and participated in Advisory Boards for Janssen and Merck. HP has participated in Advisory Boards for United Therapeutics. RRJ has received grants or consulting fees from Janssen, Bayer, United Therapeutics, and Merck. SSa has received grants or consulting fees from Merck, United Therapeutics, Gossamer, Keros, Pulmovant, Liquidia, and Respira Therapeutics, and participated in advisory boards for United Therapeutics and Liquidia. TS has received consulting fees from and participated in advisory boards for United Therapeutics and Bayer. SSh has received grants from Liquidia, Pharmosa, and Gossamer. LS has received grants from Acceleron, Gossamer, Insmed, Merck, and Liquidia. CD, MB, PS, and CT are employees of United Therapeutics. The study protocol, protocol amendments, and informed consent forms were submitted for review and approved by each site's institutional review board or independent ethics committee.

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BREEZE Optional Extension Phase: Long-term safety and efficacy of treprostinil dry powder inhaler (Tyvaso DPI) in pulmonary arterial hypertension

Affiliations

BREEZE Optional Extension Phase: Long-term safety and efficacy of treprostinil dry powder inhaler (Tyvaso DPI) in pulmonary arterial hypertension

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical