First Patient Enrolled in TETON 2 Phase 3 Trial of Tyvaso for IPF
United Therapeutics expands TETON program for idiopathic pulmonary fibrosis
The first patient has been enrolled in a Phase 3 clinical trial of Tyvaso (treprostinil) inhalation solution for patients with idiopathic pulmonary fibrosis (IPF), according to the therapy’s developer, United Therapeutics.
Called TETON 2 (NCT05255991), the trial will evaluate the treatment’s efficacy against a placebo in about 396 adults with IPF, ages 40 and older, at sites outside of the U.S. and Canada.
Tyvaso is approved in the U.S. to treat pulmonary arterial hypertension and to increase exercise capacity in pulmonary hypertension (PH) associated with interstitial lung diseases (ILD), including IPF. It is not currently approved to treat IPF patients who do not have PH.
“The expansion of the TETON program demonstrates our excitement about the potential for Tyvaso in IPF,” Peter Smith, vice president of global product development at United Therapeutics, said in a press release.
“Like with TETON 1, the TETON 2 study is an example of our flexible development model to expand beyond PH to potentially help us better understand the impact of treprostinil as a potential treatment option for this vulnerable group of patients,” added Smith.
IPF is a type of ILD, which comprises a group of diseases characterized by inflammation and fibrosis (scarring) in the lungs. As IPF advances, some patients will develop PH, a condition in which blood pressure in the arteries connecting the heart to the lungs is elevated.
“Despite the availability of two approved products in this therapeutic category, there remains a critical unmet need in IPF,” said Steven Nathan, MD, chair of the TETON program steering committee and medical director of the Advanced Lung Disease and Lung Transplant Program at Inova Fairfax Hospital, Virginia.
Tyvaso’s active ingredient, treprostinil, is a lab-made molecule designed to mimic the activity of prostacyclin, which is produced naturally in the body. Prostacylin works to widen and relax blood vessels, improving blood flow and lowering blood pressure.
Administered through a portable, hand-held device that delivers the medication directly to the lungs, Tyvaso is expected to increase blood circulation and improve exercise and breathing capacity for people with lung disease.
It was first approved in 2009 for pulmonary arterial hypertension, and was expanded in 2021 to include PH-ILD.
INCREASE clinical trial
The PH-ILD expansion was backed by data from the Phase 2/3 INCREASE trial (NCT02630316), which demonstrated that Tyvaso was superior to a placebo at improving exercise capacity in 326 adults with PH-ILD.
It also reduced acute bouts of symptom worsening (exacerbations), lowered levels of NT-proBNP — a marker of heart strain — and prevented lung function decline, as measured by changes in forced vital capacity (FVC). These lung function improvements were particularly pronounced among a subgroup of patients with IPF. Of note, FVC is a lung function parameter that measures the total amount of air a person is capable of exhaling after a deep breath.
“As is now widely known in the pulmonology community, the safety data collected from the INCREASE study showed a positive impact of inhaled treprostinil on FVC in IPF patients with pulmonary hypertension,” Nathan said.
“In follow-up to this, the TETON 1 and TETON 2 studies have been designed to further investigate the potential antifibrotic effects of inhaled treprostinil in IPF patients,” Nathan added.
In both TETON studies, participants will be assigned randomly to receive inhaled Tyvaso four times per day, or a placebo, for one year. Each inhalation delivers about 6 micrograms of treprostinil. Patients will begin with three inhalations four times per day (12 total) and be titrated up to a target of 12 inhalations four times per day, or until they reach their maximum tolerated dose.
The main goal of the TETON clinical program is to assess Tyvaso’s effect on lung function after a year of treatment, which will be assessed by changes in FVC.
Secondary goals include evaluating changes in exacerbations, survival, and a patient symptom questionnaire, as well as overall clinical worsening, defined as death, hospitalization for breathing problems, or at least a 10% decline in FVC.
Assessments for changes related to PH, including NT-proBNP levels, supplemental oxygen use, and lung capacity also will be collected.
Both TETON trials are expected to conclude in June 2025.