INHALED treprostinil slowed lung function decline in TETON-1, a Phase III trial in idiopathic pulmonary fibrosis presented at ATS 2026 in Orlando, Florida.
Inhaled Treprostinil in IPF
Presented during the Breaking News: Clinical Trial Results in Pulmonary Medicine Advance Outcomes session, TETON-1 evaluated inhaled treprostinil in patients with idiopathic pulmonary fibrosis, a progressive disease associated with reduced quality of life and premature death from respiratory failure.
The 52-week Phase III study, also known as RIN-PF-301, enrolled patients with idiopathic pulmonary fibrosis in the USA and Canada. Eligible participants had centrally reviewed IPF and a forced vital capacity of at least 45% predicted. Treatment was delivered by nebulizer four times daily, titrated from three breaths to a target dose of 12 breaths four times daily, with participants allowed to enter on background antifibrotic therapy.
TETON-1 Shows FVC Benefit
TETON-1 met its primary endpoint, showing a statistically significant placebo corrected difference of 130.1 mL in absolute forced vital capacity at Week 52. Separation between treatment and placebo emerged by Week 8 and continued through Week 52.
The FVC trajectory favored inhaled treprostinil across background therapy groups. Patients not receiving background therapy had numerically less FVC decline with inhaled treprostinil, while statistically significant benefits were observed among patients receiving nintedanib or pirfenidone. The presenter emphasized the consistency of treatment effect across these groups, rather than interpreting the no background therapy subgroup as evidence of reduced efficacy.
Clinical Worsening and Safety Findings
Inhaled treprostinil also reduced the risk of clinical worsening by 33%, based on a composite of death, respiratory hospitalization, or 10% relative reduction in FVC. Time to first acute exacerbation numerically favored inhaled treprostinil, with a 50% relative reduction, although event rates were low. Overall survival, King’s Brief Interstitial Lung Disease Questionnaire scores, and DLCO also showed numerical trends favoring inhaled treprostinil.
Adverse events were common in both arms. Cough was the most frequent adverse event, reported in 54.8% of patients receiving inhaled treprostinil and 33.1% receiving placebo. Throat irritation was also more common with inhaled treprostinil. Serious adverse events occurred in 18% of the treatment arm and 24% of the placebo arm, while study drug related serious adverse events were 3.3% in both groups.
The discontinuation rate was high, which the presenter partly attributed to the burden of nebulized therapy four times daily and “nebulizer fatigue.” Only a minority of discontinuations were attributed purely to cough. Overall, the safety profile was described as consistent with known prostacycline related adverse events.
Reference
Steven D. Nathan. TETON-1 Phase 3 Clinical Trial of Inhaled Treprostinil for the Treatment of Idiopathic Pulmonary Fibrosis. ATS International Conference, 15-20 May, 2026.
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