United Therapeutics Completes Enrollment for TETON 2 Study on Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis

United Therapeutics Corporation, a public benefit corporation listed on Nasdaq under the symbol UTHR, has announced the full enrollment of its TETON 2 study. This clinical trial is exploring the efficacy and safety of Tyvaso® (treprostinil) inhalation solution in treating idiopathic pulmonary fibrosis (IPF). The TETON 2 study is a part of a broader initiative, the TETON program, which includes three studies aimed at assessing inhaled treprostinil in IPF and progressive pulmonary fibrosis (PPF).

The TETON 2 study enrolled 597 patients, focusing on individuals outside the United States and Canada. Meanwhile, TETON 1 targets U.S. and Canadian patients with IPF, and TETON PPF evaluates the drug's impact on PPF patients globally. All three studies permit the use of nebulized Tyvaso either as monotherapy or in combination with one approved background therapy for IPF or PPF.

Dr. Peter Smith, Vice President of Product Development at United Therapeutics and the lead for the TETON program, expressed gratitude for the patients and investigators participating in the study. He emphasized the program’s objective to demonstrate that inhaled treprostinil can yield better outcomes for patients suffering from fibrotic lung diseases.

The TETON program's inception was influenced by results from the INCREASE study, which examined nebulized Tyvaso for treating pulmonary hypertension linked with interstitial lung disease (PH-ILD). The INCREASE study’s post-hoc analysis revealed significant improvements in forced vital capacity (FVC) at both 8 and 16 weeks, particularly in patients with underlying IPF. These improvements were maintained for at least 64 weeks, according to open-label extension data published in 2023.

Further, patients who initially received a placebo in the INCREASE study showed notable FVC improvements upon transitioning to nebulized Tyvaso. This, along with extensive preclinical evidence of treprostinil’s antifibrotic activity, suggests that nebulized Tyvaso might be a viable treatment for IPF and PPF patients.

Currently, Tyvaso is approved to enhance exercise ability in patients with pulmonary arterial hypertension and PH-ILD. Although Tyvaso DPI® (treprostinil) Inhalation Powder is not under evaluation in the TETON program, United Therapeutics plans to seek FDA approval to extend the Tyvaso DPI label to include IPF and PPF after the TETON studies and any required bridging studies.

The TETON 2 study is a rigorous, multicenter, randomized, double-blind, placebo-controlled phase 3 trial involving 597 patients. It aims to assess the safety and efficacy of nebulized Tyvaso over 52 weeks at sites outside the U.S. and Canada. The study reached full enrollment in July 2024, with top-line data expected in the second half of 2025. Participants are randomly assigned to receive either nebulized Tyvaso or a placebo, starting with a dose of three breaths four times daily, with the aim to titrate up to 12 breaths as tolerated.

The primary endpoint is the change in FVC from baseline to week 52. Secondary endpoints include time to clinical worsening, the first acute exacerbation of IPF, overall survival at week 52, and changes in percent-predicted FVC. Other study data will encompass plasma NT-proBNP levels, supplemental oxygen use, and lung diffusion capacity, alongside safety assessments including adverse events and vital signs.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by scarring, leading to respiratory failure and death. While its exact cause remains unknown, it rarely occurs before age 50 and is linked to factors such as smoking, genetic predispositions, and possibly acid reflux, viral infections, and air pollution. In the U.S., it affects over 100,000 people, with only two approved therapies that merely slow disease progression.

The TETON program is a significant effort by United Therapeutics to find more effective treatments for this devastating disease, potentially offering new hope to those affected by IPF and PPF.