United Therapeutics Announces Full Enrollment in TETON 1 Study of Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis
Inhaled Treprostinil United Therapeutics Corporation a public benefit corporation, recently announced the completion of full enrollment in its pivotal TETON 1 clinical study. This study is designed to evaluate the efficacy and safety of Tyvaso® (treprostinil) inhalation solution, also known as nebulized Tyvaso, as a treatment for idiopathic pulmonary fibrosis (IPF). With a total of 598 participants enrolled, the TETON 1 study is part of a broader three-study global clinical trial program called the TETON program. The program aims to assess the use of inhaled treprostinil in IPF and progressive pulmonary fibrosis (PPF), two debilitating and often fatal lung diseases.
The TETON 1 study specifically focuses on patients in the United States and Canada, making it an important milestone for United Therapeutics as it moves closer to potentially offering a novel treatment option to IPF patients in these regions. Additionally, TETON 2, a sister study to TETON 1, evaluates the use of inhaled treprostinil for IPF in patients located outside the United States and Canada, while TETON PPF assesses its efficacy in treating PPF on a global scale.
Inhaled Treprostinil Patients enrolled in any of the TETON studies are allowed to use nebulized Tyvaso either alone as a monotherapy or in combination with one background therapy approved for treating IPF or PPF. This flexible approach is significant, as it ensures that the treatments used in the trials reflect real-world clinical practices, where many patients with IPF or PPF are on multiple medications simultaneously.
Enrollment Inhaled Treprostinil for TETON 2 concluded in July 2024, with the release of top-line data from that study expected in the second half of 2025. Meanwhile, enrollment in TETON PPF continues, with the ultimate goal of further expanding our understanding of how inhaled treprostinil can be used to address the unmet needs of patients with these serious lung diseases.
A Step Toward Transformative Treatment for IPF
Peter Smith, Pharm.D., Vice President of Product Development at United Therapeutics and the lead for the global TETON program, expressed enthusiasm over the full enrollment of the TETON 1 study. “Completing enrollment in this trial brings us one step closer to potentially delivering a transformative and much-needed treatment option for this vulnerable group of patients living with IPF,” said Smith. He continued, “Each of the participants in this study represents someone seeking better outcomes and improved quality of life. Their willingness to participate, along with the commitment of our investigators, moves us forward in our mission to deliver novel therapies that address significant challenges for patients and meaningfully impact the standard of care.”
IPF is a chronic, Inhaled Treprostinil progressive lung disease that leads to scarring (fibrosis) of the lungs, making it difficult for patients to breathe and get enough oxygen. It is a debilitating condition with a poor prognosis, and there is currently no cure. Existing treatments aim to slow disease progression, but they do not address the underlying causes of fibrosis. Given the severe impact of IPF on patients’ lives and the limited treatment options available, the development of new therapies is crucial.
Supporting Data from Previous Studies
The Inhaled Treprostinil TETON program was inspired by the results of the INCREASE study, which investigated the use of nebulized Tyvaso for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD). In a post-hoc analysis of the INCREASE study, patients with IPF as an underlying cause showed the most significant improvements in percent predicted forced vital capacity (FVC), a key measure of lung function. Specifically, at week 8, the IPF patients treated with nebulized Tyvaso showed a 2.5% improvement in FVC (p=0.038), and by week 16, this improvement had increased to 3.5% (p=0.015).
In addition to these early improvements, open-label extension data published in 2023 revealed that these gains in lung function were sustained for at least 64 weeks. Furthermore, patients who had initially received a placebo in the INCREASE study showed marked improvements in FVC after transitioning to nebulized Tyvaso during the open-label extension study. These compelling results, along with substantial preclinical evidence suggesting the antifibrotic activity of treprostinil, raised the possibility that nebulized Tyvaso could offer a new treatment approach for both IPF and PPF.
TETON Program and Treprostinil
Inhaled Treprostinil, Nebulized Tyvaso is already approved for use in improving exercise capacity in patients with pulmonary arterial hypertension (PAH) and PH-ILD. However, the TETON program is evaluating nebulized Tyvaso for its potential to treat IPF and PPF, conditions for which it is not yet approved. United Therapeutics also has an investigational product, Tyvaso DPI® (treprostinil) Inhalation Powder, but this formulation is not currently being evaluated in the TETON studies.
United Therapeutics plans to seek approval from the U.S. Food and Drug Administration (FDA) to expand the Tyvaso inhalation solution label to include the treatment of IPF and PPF following the completion of the TETON studies and any additional studies required by the FDA. Tyvaso DPI is not currently approved in any jurisdiction for the treatment of IPF or PPF either.
The ultimate goal of the TETON program is to gather the clinical evidence necessary to support regulatory filings in the United States and Europe. If the TETON 1 and TETON 2 trials yield successful results, United Therapeutics intends to use the data from these studies to submit a regulatory filing with the FDA to include IPF in the labeled indications for nebulized Tyvaso. In Europe, where nebulized Tyvaso is not yet approved, the company plans to work with its international distributor, Grupo Ferrer Internacional, S.A., to support a marketing authorization application with the European Medicines Agency (EMA) for the treatment of IPF.
Next Steps in the TETON Program
As enrollment for the TETON 1 study has been completed, attention will now shift to the collection and analysis of data from participants. The TETON 2 study, which is enrolling patients outside the United States and Canada, will provide additional insights into the broader applicability of nebulized Tyvaso for treating IPF. Together, the data from these two trials, along with results from the TETON PPF study, will be pivotal in shaping the future of treatment options for IPF and PPF patients worldwide.
The potential approval of nebulized Tyvaso for IPF could have a significant impact on patient care, providing a new therapy option for a disease with a high unmet medical need. As the study progresses, the research findings will not only be crucial for regulatory approval but will also contribute to a deeper understanding of how inhaled treprostinil can benefit individuals with progressive fibrotic lung diseases.
