United Therapeutics Corporation announced full enrollment of the TETON 2 study evaluating the use of Tyvaso®? (treprostinil) inhalation solution (nebulized Tyvaso) for the treatment of idiopathic pulmonary fibrosis (IPF). The TETON 2 study enrolled 597 patients and is part of the three-study global TETON clinical trial program evaluating the use of inhaled treprostinil in IPF and a similar condition, progressive pulmonary fibrosis (PPF).

TETON 1 is evaluating the use of inhaled treprostinil in IPF in patients in the United States and Canada. TETON 2 is evaluating the use of inhaled treprostinil in IPF in patients outside the United States and Canada. TETON PPF is evaluating the use of inhaled treprostinil in PPF in patients globally.

Patients in any of the TETON program studies may use nebulized Tyvaso alone as a monotherapy or in combination with one background therapy approved for the treatment of IPF or PPF. Enrollment in TETON 1 and TETON PPF is ongoing. The TETON program in IPF and PPF was prompted by data from the INCREASE study of nebulized Tyvaso for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD), which demonstrated in a post-hoc analysis that treatment with nebulized Tyvaso resulted in significant improvements in percent predicted forced vital capacity (FVC) at weeks 8 and 16, with subjects having an underlying etiology of IPF showing the greatest improvement (week 8: 2.5%; p=0.038 and week 16: 3.5%; p=0.015).

Further, open label extension data published in 2023 showed these improvements in FVC were sustained for at least 64 weeks. For those patients who received placebo during the INCREASE study, marked improvements in FVC were observed following transition to nebulized Tyvaso during the open-label extension study. These data points, combined with substantial preclinical evidence of antifibrotic activity of treprostinil, suggest that nebulized Tyvaso may offer a treatment option for patients with IPF and PPF.

The TETON program is evaluating the use of nebulized Tyvaso, which is approved to improve exercise ability in patients with pulmonary arterial hypertension and PH-ILD. Tyvaso DPI® (treprostinil) Inhalation Powder is not being evaluated in the TETON program, but United Therapeutics intends to seek U.S. Food and Drug Administration (FDA) approval to expand the Tyvaso DPI label to include IPF and PPF following completion of the TETON studies and any FDA-required bridging studies. Tyvaso Inhalation Solution and Tyvaso DPI are not approved in any jurisdiction for the treatment of IPF or PPF patients who do not have documented pulmonary hypertension.

The TETON 2 study is a 597-patient, multicenter, randomized, double-blind, placebo-controlled phase 3 registration study to evaluate the safety and efficacy of nebulized Tyvaso in subjects with IPF over a 52-week period at sites outside of the United States and Canada. The study reached full enrollment in July 2024 and top-line data is expected in the second half of 2025. Subjects will be randomly allocated 1:1 to receive nebulized Tyvaso or placebo.

All subjects will initiate nebulized Tyvaso or placebo at a dose of three breaths administered four times daily (QID) and will titrate to a target dosing regimen of 12 breaths QID. Study drug doses may be titrated up as tolerated, until the target dose or maximum clinically tolerated dose is achieved. The primary endpoint of the study is the change in FVC from baseline to week 52.

Secondary endpoints include: (1) time to clinical worsening; (2) time to first acute exacerbation of IPF; (3) overall survival at week 52; (4) change in percent predicted FVC from baseline to week 52; and (5) change in the King?s Brief Interstitial Lung Disease questionnaire. Other data collected in the study will include the plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration, supplemental oxygen use, and lung diffusion capacity. Safety assessments include the development of adverse events, serious adverse events, vital signs, clinical laboratory parameters, and electrocardiogram parameters.