Treprostinil Inhalation Significantly Improves FVC in People With Idiopathic Pulmonary FIbrosis

The TETON-2 study of treprostinil inhalation solution has met its primary efficacy endpoint of demonstrating improvement in absolute forced vital capacity (FVC) in people with idiopathic pulmonary fibrosis (IPF).1

“As clinicians, we witness firsthand the devastating impact of IPF, with limited therapies to offer these vulnerable patients under our care,” Steven D. Nathan, MD, Schar Chair, Advanced Lung Disease and Lung Transplant Program at Inova Fairfax Hospital and Chair of the TETON Steering Committee, said in a statement.1 “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. These unequivocally positive results included endpoints that were not attained in prior phase 3 IPF clinical trials — including, importantly, a difference in quality of life. It is also notable that most patients were already on standard of care anti-fibrotic therapy, which makes these results even more impressive. We are especially excited for our patients, as these results offer a renewed sense of hope.”

Treprostinil demonstrated superiority over placebo for the change in absolute FVC by 95.6 mL (Hodges-Lehmann estimate, P <.0001) from baseline to week 52 in patients with IPF across subgroups of background therapy use (nintedanib, pirfenidone, or no background therapy), smoking status, and supplemental oxygen use.

Investigators also observed improvements in most secondary endpoints, including time to first clinical worsening event, as well as 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) compared to placebo. Time to first acute exacerbation of IPF and overall survival at week 52 trended in favor of treprostinil, although this was not significant. Treprostinil was well-tolerated with a safety profile consistent with previous studies and known prostacyclin-related adverse events and no new safety signals.

“It is a profound honor to witness the power of scientific innovation realized for patients in need,” Martine Rothblatt, PhD, Chairperson and Chief Executive Officer of United Therapeutics, added.1 “TETON-2’ssuccessful outcomeaffirms the anti-fibrotic power of Tyvaso. We have unlocked new hope for patients with IPF and their families.”

TETON-2 study (NCT05255991) was a multicenter, randomized, double-blind, placebo-controlled phase 3 registration study that evaluated the safety and efficacy of nebulized treprostinil in 597 people with IPF over a 52-week period at sites in Argentina, Australia, Belgium, Chile, Denmark, France, Germany, Israel, Italy, Mexico, the Netherlands, New Zealand, Peru, South Korea, Spain, and Taiwan.

Participants were randomly assigned 1:1 to receive nebulized treprostinil or placebo at a dose of 3 breaths administered 4 times daily (QID) and titrated to a target dosing regimen of 12 breaths QID, stratified by IPF background therapy use, and titrated up as tolerated until reaching the target dose or maximum clinically tolerated dose. Participants that completed TETON-2 could enroll in the ongoing TETON-OLE study (NCT04905693) open-label extension study. Further data from TETON-2 study will be presented at the European Respiratory Society Congress in late September in Amsterdam.

Data from TETON-2, as well as from the ongoing TETON-1 study, are intended to support support a supplemental New Drug Application to the FDA to add IPF to the labeled indications for nebulized Treprostinil, currently approved under the name Tyvaso, for the treatment of pulmonary arterial hypertension in 2022.2

United Therapeutics intends to use the 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 to add IPF to the labeled indications for nebulized Tyvaso. United Therapeutics 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 are 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.1

“These overwhelmingly positive data send a clear signal of the potential benefits of Tyvaso for patients with IPF,” Peter Smith, PharmD, Senior Vice President, Product Development at United Therapeutics and the lead for the global TETON program, added.1 “We are deeply grateful to every patient who participated in this important study and the investigators whose dedication made this milestone possible. These results have the potential to reshape the treatment of IPF, extending new opportunities to a much broader patient population than ever before.”

References

1. United Therapeutics Corporation Announces TETON-2 Pivotal Study of Tyvaso® Meets Primary Endpoint for the Treatment of Idiopathic Pulmonary Fibrosis. News release. United Therapeutics. September 2, 2025. https://ir.unither.com/press-releases/2025/09-02-2025-120037033

2. United Therapeutics Announces FDA Approval of Tyvaso DPI™. News release. United Therapeutics. May 24, 2022. https://ir.unither.com/press-releases/2022/05-24-2022