With the publication of the phase 3 TETON-1 trial investigating inhaled treprostinil for patients with idiopathic pulmonary fibrosis (IPF) earlier this year, the pulmonology community saw a treatment effect that compared favorably with lung-function declines reported in landmark trials of currently approved antifibrotic therapies, reflecting a potentially important advancement in treatment.1
The TETON-1 study, which compared inhaled treprostinil with placebo, met its primary end point. Patients receiving treprostinil experienced a substantially smaller decline in FVC than those receiving placebo. The median decline at 52 weeks was 43.3 mL in the treprostinil group compared with 196.2 mL in the placebo group. Treprostinil was also associated with a significant reduction in clinical worsening events.
“A 130 mL a year difference in FVC decline is quite meaningful,” said Christopher King, MD, FCCP, investigator and Chief of Cardiovascular Critical Care at Inova Schar Heart and Vascular Institute. “I would think about it in terms of the impact this may have on time to development of symptoms, need for oxygen, need for transplant, et cetera, as the years stack up.”
Dr. King said the treatment effect compares favorably with declines reported in landmark trials of currently approved antifibrotic therapies and reflects a potentially important advancement for patients with a progressive disease that remains incurable.
Beyond the effect on lung function, investigators highlighted the reduction in clinical worsening events, a composite end point that included death, respiratory hospitalization, or a substantial decline in lung function.
“I think the effects on clinical worsening make the data even more compelling,” Dr. King said. “Decline in FVC is a surrogate marker for progression but has been shown to correlate with mortality in IPF. The fact that it reduces clinical worsening events further supports the clinical impact of the treatment.”
The results also suggest a possible future that may increasingly include combination approaches for managing IPF. Inhaled treprostinil could complement existing oral therapies rather than compete directly with them, Dr. King said.
Steven D. Nathan, MD, FCCP, lead investigator of the TETON program, echoed that perspective, suggesting that inhaled therapies could provide advantages by delivering medication directly to affected regions of the lung.
“I think where we’re going in the future is combination therapy,” said Dr. Nathan, who is Medical Director of the Advanced Lung Disease and Transplant Program at Inova Fairfax Hospital in Northern Virginia. “It makes a lot of sense that patients should be on an oral therapy and then supplement that with something inhaled.”
Indeed, local drug delivery may help explain the strong efficacy signal observed in the TETON studies.
“I think the very strong efficacy signal emerging from the TETON studies, including five of six secondary end points being met in the combined dataset, was the fact that there was more local deposition and more drug going to the actionable areas at the alveolar level,” Dr. Nathan said.
Safety findings were generally consistent with previous studies. Adverse events occurred in more than 90% of participants, with cough reported most. Treatment discontinuation due to adverse events was higher in the treprostinil arm, although serious adverse events were somewhat less common than with placebo.
However, Dr. King said, the discontinuation findings should be interpreted carefully.
“I think the high discontinuation rate is notable, but should be interpreted in the correct context,” he said. “Our center’s discontinuation rate was lower, showing that with proper coaching and counseling, patients can stay on treatment.”
Dr. Nathan agreed. “We now have very compelling data as to the efficacy of the drug, so I think patients will be more inclined to stick with it, and doctors will be more inclined to encourage their patients to stick with it,” he said.
Questions remain regarding optimal dosing schedules and strategies to reduce cough and improve tolerability. Dr. Nathan said that future research should explore whether lower-frequency dosing might maintain efficacy while improving convenience.
References
1. Nathan SD, Smith P, Deng C, et al. Phase 3 trials of inhaled treprostinil for idiopathic pulmonary fibrosis. N Engl J Med. 2026; 395:115-126. doi:10.1056/NEJMoa2501488
