TETON-1: Treprostinil Preserved Lung Function in Idiopathic Pulmonary Fibrosis

New phase 3 data presented at the 2026 American Thoracic Society (ATS) International Conference in Orlando, Florida, and simultaneously published in the New England Journal of Medicine, showed inhaled treprostinil preserved lung function and reduced the risk of clinical worsening in patients with idiopathic pulmonary fibrosis (IPF).1

The findings from the TETON-1 trial demonstrated that nebulized treprostinil (Tyvaso) met both its primary endpoint, which was a change in absolute forced vital capacity (FVC) from baseline to week 52, and several secondary endpoints, according to United Therapeutics. Investigators reported that median FVC decline at week 52 was −43.3 mL in the nebulized treprostinil arm (95% confidence interval [CI], −92.1 to −9) compared with −196.2 mL with placebo (95% CI, −227.1 to −155.6), translating to a between-group difference of 130.1 mL (95% CI, 82.2 to 178.1; P <.001).

As for the key secondary endpoint, the study showed that nebulized treprostinil reduced the risk of a clinical worsening event by 33% relative to placebo (hazard ratio [HR], 0.67; 95% CI, 0.52-0.88; P =.0034). Additional secondary endpoints numerically favored treatment with nebulized treprostinil, including percent predicted FVC, quality of life assessed by the King’s Brief Interstitial Lung Disease questionnaire, and diffusion capacity of the lungs for carbon monoxide.

According to investigators, treatment effects were observed across patient subgroups, including those receiving background antifibrotic therapy with nintedanib or pirfenidone, as well as patients not receiving background therapy.

“The results of TETON-1 validate what was seen in TETON-2,” said Steven D. Nathan, MD, chair of the TETON Steering Committee and Schar chair of the Advanced Lung Disease and Lung Transplant Program at Inova Fairfax Hospital, in a statement. “The meaningful effect on FVC decline observed across all subgroups, as well as achieving positive results for five out of six secondary endpoints in the combined analysis, is truly impressive for a 52-week treatment duration.”

Combined analyses from TETON-1 and TETON-2 similarly favored nebulized treprostinil. Median FVC decline at week 52 was −45.4 mL in the treatment group (95% CI, −73.8 to −23.1) versus −161.7 mL with placebo (95% CI, −194.5 to −134.1), corresponding to a between-group difference of 111.8 mL (95% CI, 79.7 to 144; P <.0001).

Across the pooled analysis, nebulized treprostinil reduced the risk of clinical worsening by 31% (HR, 0.69; 95% CI, 0.57 to 0.84; P =.0002) and reduced the risk of acute IPF exacerbation by 48% (HR, 0.52; 95% CI, 0.30 to 0.91; P =.0223). Investigators also reported statistically significant improvements in percent predicted FVC, quality-of-life scores, and DLCO.

Although overall survival at week 52 numerically favored treprostinil, the difference did not reach statistical significance.

IPF is a progressive fibrotic lung disease characterized by worsening lung function and respiratory failure; most patients die within 3 to 5 years following diagnosis. Existing approved therapies, including nintedanib and pirfenidone, slow disease progression but do not reverse fibrosis. According to United Therapeutics, nebulized treprostinil may offer a differentiated mechanism by targeting fibrotic, vascular, and inflammatory pathways through direct lung delivery.

“The profound impact of the TETON clinical program in IPF, with combined results showing significantly improved preservation of lung function and quality of life, as well as reductions in disease worsening and acute IPF exacerbations, represents a truly important advancement for people living with this progressive, life-threatening disease,” said Martine Rothblatt, PhD, chief executive officer of United Therapeutics, in a statement.

The TETON-1 trial enrolled 598 patients with IPF across sites in the US and Canada. The randomized, double-blind, placebo-controlled phase 3 study evaluated nebulized treprostinil over 52 weeks. Eligible patients may continue into the ongoing TETON-OLE open-label extension study.

The therapy remains investigational for IPF and has not been approved by the FDA for this indication. However, United Therapeutics stated it plans to submit a supplemental New Drug Application to the FDA by the end of summer 2026 and seek priority review for the addition of IPF to treprostinil’s labeled indications.

References

1. United Therapeutics Corporation Announces TETON-1 Study of Tyvaso Published in The New England Journal of Medicine and Presented at ATS 2026. Unither.com. Published 2026. Accessed May 20, 2026. https://ir.unither.com/press-releases/2026/05-18-2026-211528317

2. Fernández Fabrellas E, Peris Sánchez R, Sabater Abad C, Juan Samper G. Prognosis and Follow-Up of Idiopathic Pulmonary Fibrosis. Med Sci (Basel). 2018;6(2):51. Published 2018 Jun 14. doi:10.3390/medsci6020051