The United States (US) Food and Drug Administration (FDA) has accepted a supplemental new drug application from United Therapeutics for nebulized treprostinil (Tyvaso)) Inhalation Solution to treat idiopathic pulmonary fibrosis (IPF), based on positive phase 3 data from the combined TETON-1 and TETON-2 trials.1
Nebulized treprostinil would become the first and only inhaled anti-fibrotic treatment for IPF if the FDA approves the expanded indication, according to United Therapeutics.1 The agency's review is expected to be complete in late April 2027. Both the FDA and the European Medicines Agency have already granted orphan designation to treprostinil for IPF.1
“Nebulized Tyvaso combines direct lung delivery with multimodal activity across fibrotic, vascular, and inflammatory pathways central to IPF, with the potential to help address a significant unmet need for this life-threatening disease,” said Martine Rothblatt, PhD, chairperson and CEO of United Therapeutics.1 “We're galvanized by the FDA's acceptance of the nebulized Tyvaso sNDA for review and believe the strength and rigor of our TETON clinical program support an approvable application for this differentiated multi-pathway treatment for patients managing this life-threatening disease.”
What was the efficacy in TETON-1 and TETON-2?
TETON-1 and TETON-2 are multicenter, randomized, double-blind, placebo-controlled phase 3 registration studies evaluating nebulized Tyvaso in patients with IPF over 52 weeks. TETON-1 enrolled patients in the US and Canada, and TETON-2 enrolled patients outside the US and Canada. Both trials share a primary endpoint of change in absolute forced vital capacity (FVC) from baseline to week 52.1
The program builds on a post-hoc analysis of the INCREASE trial in pulmonary hypertension associated with interstitial lung disease, which suggested nebulized Tyvaso improved FVC in this population.1 In the combined analysis of TETON-1 and TETON-2, nebulized Tyvaso met the primary endpoint, showing statistically significant superiority over placebo for change in absolute FVC, with a Hodges-Lehmann estimate of 111.8 mL (95% CI, 79.7-144.0 mL; P <.0001) from baseline to week 52 in an IPF population broadly treated with background therapy.1
Nebulized Tyvaso secondary endpoints and safety
United Therapeutics reported the combined TETON-1 and TETON-2 analyses achieved statistical significance for most key secondary endpoints.1 These included a reduced risk of a clinical worsening event, a reduced risk of an acute IPF exacerbation, and changes in percent predicted FVC, the King's Brief Interstitial Lung Disease questionnaire, and diffusion capacity of the lungs for carbon monoxide.1 The company's release did not report new safety findings specific to the idiopathic pulmonary fibrosis population studied in TETON-1 and TETON-2.
Patients completing TETON-1 and TETON-2 were eligible to enroll in TETON-OLE, an ongoing open-label extension study evaluating the long-term safety and tolerability of nebulized treprostinil in fibrotic lung disease.1 Nebulized treprostinil remains investigational for idiopathic pulmonary fibrosis and has not been approved by the FDA for this indication.
United Therapeutics is also running TETON-PPF, a global study of nebulized treprostinil in progressive pulmonary fibrosis, for which enrollment is now complete.1 TETON-1 data were presented at the 2026 American Thoracic Society meeting, and TETON-2 data along with the combined TETON-1/TETON-2 analysis were published in The New England Journal of Medicine.2 Treprostinil is already FDA approved to improve exercise ability in pulmonary arterial hypertension and in pulmonary hypertension associated with interstitial lung disease.
References
United Therapeutics Corporation. United Therapeutics Corporation announces FDA acceptance of supplemental New Drug Application for nebulized Tyvaso to treat idiopathic pulmonary fibrosis. Published September 2, 2026. Accessed September 3, 2026. https://ir.unither.com/press-releases/2026/09-02-2026-120033661
Nathan SD, Smith P, Deng C, et al. Phase 3 trials of inhaled treprostinil for idiopathic pulmonary fibrosis. N Engl J Med. Published online May 18, 2026. doi:10.1056/NEJMoa2501488
