Combined results of the TETON-1 and TETON-2 Trials of Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis.

BACKGROUND: Inhaled treprostinil has been shown to slow the rate of loss of lung function in IPF patients in two independent studies. A detailed analysis of the fully integrated results of both studies will provide more precise and robust estimates of the drug's efficacy in IPF. METHODS: TETON-1 and TETON-2 were two replicate phase 3 double-blind trials, where patients with IPF were randomized to inhaled treprostinil or placebo. The primary endpoint was change in absolute forced vital capacity (FVC) at week 52. Secondary outcomes were time to clinical worsening, time to IPF exacerbation, survival, percent predicted FVC (ppFVC), quality of life and percent predicted diffusing capacity (ppDLCO) by 52 weeks. RESULTS: There were 1191 patients who underwent randomization and received at least one dose of treprostinil (597 patients) or placebo (594 patients) across both trials. Median change from baseline in FVC was -45.4 ml (95% CI, -73.8 to -23.1) in the treprostinil group and -161.7 ml (95% CI, -194.5 to -134.1) in the placebo group (between-group difference 111.8 ml (95% CI, 79.7 to 144.0, p < 0.0001) at 52 weeks. Treprostinil demonstrated superiority to placebo in five of six secondary efficacy endpoints including: time to first clinical worsening, time to first IPF exacerbation, change from baseline in the K-BILD, ppDLCO, and ppFVC. There were 41 (6.9%) deaths in the inhaled treprostinil group versus 56 (9.4%) deaths in the placebo group. Cough was the most common adverse event. CONCLUSIONS: Inhaled treprostinil slowed the rate of lung function loss, delayed clinical worsening and IPF exacerbations, and demonstrated benefits in DLCO and quality of life over 52 weeks. The results support the use of inhaled treprostinil in patients with IPF.(Funded by United Therapeutics Corp; ClinicalTrials.gov number, NCT04708782 for TETON-1 and NCT05255991 for TETON-2).