First patient enrolled in TETON PPF study of nebulized Tyvaso
Study will evaluate how safe Tyvaso is, how well it improves lung function
The first patient has been enrolled in a Phase 3 clinical trial of nebulized Tyvaso (treprostinil) inhalation solution for treating progressive pulmonary fibrosis (PPF), according to United Therapeutics, the therapy’s developer.
Called TETON PPF (NCT05943535), the study will evaluate how safe Tyvaso is versus a placebo and how well it improves lung function in up to 698 adults with PPF, ages 18 and older. It’s expected to run at a number of sites around the world, according to the company.
“The initiation of the global TETON PPF study illustrates confidence in nebulized Tyvaso as a potential treatment option for patients with fibrotic lung disease,” Natalie Breytenbach, associate director of global product development at United Therapeutics, said in a company press release. “The expansion of TETON into the PPF patient population allows us to continue to evaluate inhaled treprostinil’s potential for treating this vulnerable group of patients in a robust global pivotal study.” Breytenbach is also the company’s lead for TETON PPF.
Tyvaso is approved in the U.S. to treat pulmonary arterial hypertension and to improve exercise ability in people with pulmonary hypertension associated with interstitial lung disease, a condition wherein blood pressure increases in the lungs as a result of inflammation and tissue scarring, called fibrosis.
Testing Tyvaso in PPF
Pulmonary fibrosis is a form of interstitial lung disease where scarring makes it hard for patients to breathe, leading to shortness of breath, fatigue, and a dry, hacking cough. PPF usually refers to worsening, self-sustaining scarring that leads to poor outcomes despite treatment.
People with PPF “only have limited treatment options currently available to them,” said Steven Nathan, MD, medical director of the Advanced Lung Disease and Lung Transplant Program at Inova Fairfax Hospital in Falls Church, Virginia.
Tyvaso contains treprostinil, a lab-made compound that mimics the activity of prostacyclin, a hormone naturally produced in the body. Administered via a portable, hand-held nebulizer, Tyvaso is inhaled directly into the lungs. Like prostacyclin, it widens and relaxes blood vessels, improving blood flow and reducing blood pressure.
While Tyvaso isn’t approved for people with interstitial lung disease who don’t have pulmonary hypertension, TETON PPF will test it in those with PPF regardless of whether they have high blood pressure in the lungs.
The participants will be randomly assigned to receive either nebulized Tyvaso or a placebo over 52 weeks, or about a year. Both groups will start with three breaths four times a day and gradually increase to a target of 12 breaths four times a day, as tolerated. Each breath delivers about 6 mg of treprostinil.
The study’s main goal is to assess changes in forced vital capacity (FVC), a lung function parameter that measures the total amount of air a person can exhale after a deep breath, over 52 weeks.
Secondary measures include evaluating the time to clinical worsening or first acute exacerbation (worsening) of symptoms, survival, and other measures of lung and heart function. Data on side effects and vital signs also will be collected.
The company also is running two separate registration-phase studies, TETON (NCT04708782) and TETON 2 (NCT05255991), of nebulized Tyvaso in adults with idiopathic pulmonary fibrosis (IPF), a form of pulmonary fibrosis where the underlying cause is unknown.
The TETON program for IPF and PPF stems from data from INCREASE (NCT02630316), a Phase 2/3 clinical trial where Tyvaso was found to outperform a placebo at improving exercise capacity in adults with pulmonary hypertension associated with interstitial lung disease.
It also reduced exacerbations and improved lung function, with the greatest improvements in FVC seen in a subset of people with IPF. The improvements in FVC were maintained for at least 64 weeks, or about 1.2 years.
“The data provide the foundation for further study of inhaled treprostinil’s anti-fibrotic and disease modifying mechanism of action in patients with other forms of fibrotic lung disease like PPF,” said Nathan, who’s also chair of the TETON program steering committee.