B95-09 TETON Phase 3 Clinical Trials of Inhaled Treprostinil for the Treatment of Idiopathic Pulmonary Fibrosis: Integrated Efficacy and Safety Results for TETON-1 and TETON-2

Rationale

Idiopathic pulmonary fibrosis (IPF) greatly impacts quality of life and eventually leads to premature death from respiratory failure. Inhaled treprostinil was studied in IPF based upon preclinical evidence of an antifibrotic mechanism and supportive clinical observation.

Methods

The TETON IPF program consists of two replicate, 52-week, phase 3 studies (TETON-1: RIN-PF-301; TETON-2: RIN-PF-303). Each study enrolled participants with IPF and a forced vital capacity (FVC) ≥45% predicted. The primary endpoint was change in absolute FVC at week 52. Secondary endpoints included time to clinical worsening, time to acute exacerbation of IPF, overall survival, Kings Brief Interstitial Lung Disease Questionnaire (K-BILD), and lung diffusing capacity (DLCO). An integrated analysis of TETON-1 and TETON-2 data will be conducted to strengthen safety and efficacy evaluations.

Results

TETON-1 completed enrollment in January 2025. Headline results are expected in the first half of 2026. An integrated analysis of TETON-1 and TETON-2 data will be presented. Baseline demographics from both studies are presented in Table 1.TETON-2 completed in July 2025, enrolling 597 participants with IPF. The study met its primary endpoint, with the inhaled treprostinil group declining significantly less than the placebo group for the change in absolute FVC from baseline to Week 52 (Hodges-Lehmann estimate of location shift [95% CI]: 95.6 mL [52.2, 139.0]; p < 0.0001). There was also a 29% overall reduction in the risk of experiencing a clinical worsening event (hazard ratio [95% CI]: 0.71 [0.53, 0.95]; p = 0.0190), a 46% numerical reduction in the risk of acute exacerbation of IPF, and a 23% reduction in the risk of death. Change from baseline in % predicted FVC declined significantly less at Week 52 (2.7; p < 0.0001). Change from baseline in patient reported K-BILD total score at Week 52 declined significantly less (2.29; p = 0.0124). In addition, change from baseline in both absolute and % predicted DLCO at Week 52 declined significantly less (0.15; p = 0.0309 and 1.91%; p = 0.0416, respectively). The safety profile was consistent with previous studies of inhaled treprostinil.

Conclusions

TETON-2 demonstrated superiority of inhaled treprostinil over placebo for the primary endpoint. Treatment with inhaled treprostinil was well-tolerated, and the safety profile was consistent with previous inhaled treprostinil studies and known prostacyclin-related adverse events. TETON-1 results will be available in the first half of 2026. Once TETON-1 is complete, data from both trials will be integrated to provide a broader evaluation of the efficacy and safety of inhaled treprostinil in patients with IPF.

This abstract is funded by: United Therapeutics Corporation