United’s Tyvaso Delivers Positive Phase 3 Results in IPF

United Therapeutics Corporation reported positive results from the Phase 3 TETON-2 trial evaluating nebulized Tyvaso (Treprostinil) in patients with idiopathic pulmonary fibrosis (IPF), demonstrating significant improvements in lung function and reduced risk of disease worsening over 52 weeks. The full trial results have also been published in the New England Journal of Medicine.

The randomized, placebo-controlled study met its primary endpoint, showing that treatment with nebulized Tyvaso significantly improved absolute forced vital capacity (FVC) compared with placebo from baseline to week 52.

At week 52, the median change in FVC was −49.9 mL (95% CI −79.2 to −19.5) in the Tyvaso group compared with −136.4 mL (95% CI −172.5 to −104.0) in the placebo group. The between-group difference was 95.6 mL (95% CI 52.2 to 139.0; P<0.001), indicating a meaningful slowing of lung function decline in treated patients.

Nebulized Tyvaso also significantly reduced the risk of clinical worsening events by 29% compared with placebo (hazard ratio 0.71; 95% CI 0.53–0.95; P=0.02), achieving statistical significance for this key secondary endpoint.

Additional secondary outcomes showed improvements in percent predicted FVC, lung gas exchange measured by diffusion capacity for carbon monoxide (DLCO), and patient-reported quality of life assessed using the King’s Brief Interstitial Lung Disease questionnaire (K-BILD).

Clinical benefits were observed across multiple patient subgroups, including those receiving background antifibrotic therapy such as nintedanib or pirfenidone, as well as across smoking status and supplemental oxygen use.

Steven D. Nathan, M.D., chair of the TETON steering committee and director of the Advanced Lung Disease and Lung Transplant Program at Inova Fairfax Hospital, said the findings demonstrate clinically meaningful improvements in lung function, gas exchange, and quality of life in patients with mild-to-moderate IPF treated for one year.

The Phase 3 TETON-2 study (NCT05255991) enrolled 597 patients with IPF across multiple international sites. Participants had a mean age of 71.7 years, and 80.1% were male. Baseline percent predicted FVC averaged 76.8%, and approximately 75.4% of patients were receiving background antifibrotic therapy.

Patients were randomized 1:1 to receive nebulized Tyvaso (n=298) or placebo (n=295) for 52 weeks. Treatment was initiated at three breaths four times daily and titrated to a target dose of 12 breaths four times daily as tolerated.

Patients who completed the TETON-2 study were eligible to enroll in TETON-OLE (NCT04905693), an ongoing open-label extension study designed to evaluate the long-term safety and tolerability of nebulized Tyvaso in patients with fibrotic lung disease.

Nebulized Tyvaso was generally well tolerated, with a safety profile consistent with previously reported studies of prostacyclin therapies. The most common adverse events included cough, headache, and diarrhea, which were mostly mild to moderate in severity. No new safety signals were observed.

The TETON-2 findings build on earlier observations from a post-hoc analysis of the INCREASE trial in pulmonary hypertension associated with interstitial lung disease, which suggested inhaled treprostinil may improve lung function. These findings led to the broader TETON clinical development program evaluating Tyvaso in fibrotic lung diseases.

The program includes the ongoing TETON-1 trial in IPF patients in the United States and Canada and the TETON-PPF study assessing the therapy in progressive pulmonary fibrosis.

Based on the emerging data, United Therapeutics plans to submit a supplemental New Drug Application to the U.S. Food and Drug Administration in the second half of 2026 seeking to expand the label of Tyvaso to include idiopathic pulmonary fibrosis, pending results from the TETON-1 trial. Both the FDA and the European Medicines Agency have granted orphan drug designation for treprostinil for the treatment of IPF.

Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease characterized by irreversible scarring of lung tissue, leading to declining lung function and respiratory failure. The disease typically affects adults over the age of 50 and is associated with risk factors including smoking, genetic susceptibility, environmental exposures, and gastroesophageal reflux. More than 100,000 people in the United States are estimated to be living with IPF.

For additional safety information, including adverse reactions, drug interactions, warnings, and precautions, refer to the Full Prescribing Information for Tyvaso.

Reference

United Therapeutics Corporation Announces Full Results of TETON-2 Phase 3 Clinical Trial Published in The New England Journal of Medicine, 11 March 2026, United Therapeutics Corporation Announces Full Results of TETON-2 Phase 3 Clinical Trial Published in The New England Journal of Medicine – United Therapeutics Investor Relations

Multinational Study of Efficacy and Safety of Inhaled Treprostinil in Subjects with Idiopathic Pulmonary Fibrosis (TETON-2), ClinicalTrials.gov ID NCT05255991, Study Details | NCT05255991 | Multinational Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis | ClinicalTrials.gov

 Nathan SD et al, Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. N Engl J Med. 2026 Mar 11. doi: 10.1056/NEJMoa2512911. Epub ahead of print. PMID: 41812190, https://doi.org/10.1056/nejmoa2512911