United Therapeutics Corporation announced that its pivotal TETON-2 study evaluating nebulized Tyvaso (treprostinil) Inhalation Solution for idiopathic pulmonary fibrosis (IPF) treatment successfully met its primary efficacy endpoint. The phase 3 trial demonstrated a statistically significant improvement in absolute forced vital capacity (FVC) of 95.6 mL compared to placebo (Hodges-Lehmann estimate, p <0.0001) from baseline to week 52 in IPF patients.
Study Design and Patient Population
The TETON-2 study (NCT05255991) was a 597-patient, multicenter, randomized, double-blind, placebo-controlled phase 3 registration study conducted over 52 weeks across 16 countries including Argentina, Australia, Belgium, Chile, Denmark, France, Germany, Israel, Italy, Mexico, the Netherlands, New Zealand, Peru, South Korea, Spain, and Taiwan. The study achieved full enrollment in July 2024.
Patients were randomly assigned 1:1 to receive nebulized Tyvaso or placebo, stratified by IPF background therapy use. All subjects initiated treatment at a dose of three breaths administered four times daily and titrated to a target dosing regimen of 12 breaths four times daily, with doses titrated up as tolerated until the target dose or maximum clinically tolerated dose was achieved.
Efficacy Across Multiple Endpoints
Benefits of Tyvaso were observed across all patient subgroups, including those using background therapy (nintedanib, pirfenidone, or no background therapy), different smoking statuses, and supplemental oxygen use. The study achieved statistical significance in most secondary endpoints, including time to first clinical worsening event and changes from baseline to week 52 in percent predicted FVC, King's Brief Interstitial Lung Disease quality of life questionnaire (K-BILD), and diffusion capacity of lungs for carbon monoxide (DLCO).
While not reaching statistical significance, both time to first acute exacerbation of IPF and overall survival at week 52 trended in favor of Tyvaso treatment.
Clinical Significance and Expert Commentary
"These overwhelmingly positive data send a clear signal of the potential benefits of Tyvaso for patients with IPF," said Peter Smith, Pharm.D., Senior Vice President, Product Development at United Therapeutics and lead for the global TETON program. "These results have the potential to reshape the treatment of IPF, extending new opportunities to a much broader patient population than ever before."
Steven D. Nathan, M.D., Schar Chair, Advanced Lung Disease and Lung Transplant Program at Inova Fairfax Hospital and Chair of the TETON Steering Committee, emphasized the clinical need: "Existing IPF treatments offer only modest benefits, often with challenging side effects. These results represent a major step forward, giving us hope for improving outcomes in patients who desperately need better options."
Dr. Nathan noted that the positive results included endpoints not attained in prior phase 3 IPF clinical trials, particularly the difference in quality of life measures. He highlighted that most patients were already receiving standard of care anti-fibrotic therapy, making the results even more impressive.
Safety Profile
Treatment with Tyvaso was well-tolerated, with a safety profile consistent with previous Tyvaso studies and known prostacyclin-related adverse events. No new safety signals were identified during the study period.
Regulatory Strategy and Next Steps
United Therapeutics intends to use data from both the TETON-2 study and the ongoing TETON-1 study of nebulized Tyvaso (NCT04708782) to support a supplemental New Drug Application to the FDA for adding IPF to Tyvaso's labeled indications. The company plans to meet with the FDA before the end of the year to discuss ways to potentially expedite the regulatory review process when TETON-1 results become available. Data readout from TETON-1 is expected in the first half of 2026.
Both the FDA and the European Medicines Agency have granted orphan designation for treprostinil to treat IPF. Additional TETON-2 study results will be presented at the European Respiratory Society Congress in Amsterdam on September 28, 2025.
Disease Background and Market Impact
Idiopathic pulmonary fibrosis is a scarring disease of the lungs of unknown cause and represents the most common of the idiopathic interstitial pneumonias. IPF is characterized by progressive loss of the lungs' ability to transfer oxygen into the blood, ultimately resulting in respiratory failure and death. The disease rarely presents before age 50 and can be associated with cigarette smoking and certain genetic dispositions.
According to recent research cited by United Therapeutics, IPF affects between 0.33 and 4.51 people per 10,000 persons worldwide, with the company estimating over 100,000 IPF patients in the United States alone.
Martine Rothblatt, Ph.D., Chairperson and Chief Executive Officer of United Therapeutics, stated: "TETON-2's successful outcome affirms the anti-fibrotic power of Tyvaso. We have unlocked new hope for patients with IPF and their families."
