Inhaled Treprostinil in Idiopathic Pulmonary Fibrosis: Phase 3 Data

Key Takeaways

• Median forced vital capacity decline at week 52 was smaller with treprostinil than with placebo.
• Clinical worsening occurred in 31.8% versus 44.5%, with a hazard ratio of 0.67, and no significant difference was seen in time to IPF exacerbation.
• Cough was the most frequent adverse event, and treatment discontinuation was more common with treprostinil than with placebo.

In a phase 3 randomized comparison in idiopathic pulmonary fibrosis, inhaled treprostinil was associated with a 130.1-ml smaller decline in forced vital capacity than placebo at week 52. The between-group estimate had a 95% confidence interval of 82.2 to 178.1, and the reported P value was less than 0.001. The primary end point was change in forced vital capacity at week 52 in a double-blind population assigned to active therapy or placebo.

The TETON-1 phase 3 trial randomly assigned patients with idiopathic pulmonary fibrosis to inhaled treprostinil or placebo at 12 breaths four times daily. A total of 598 patients received at least one dose, with 299 in each group, and 434 completed week 52 assessments, including 218 and 216 patients, respectively. Mean age was 73.0 years, 77.3% were men, 77.6% were receiving background antifibrotic therapy, and baseline percentage predicted FVC was 74.6%. The primary end point was change in FVC at week 52, and prespecified secondary end points were analyzed in a prespecified order to control for multiplicity. These measures included clinical worsening, acute exacerbation, survival, change in percentage predicted FVC, quality of life, and change in diffusion capacity of the lungs for carbon monoxide.

At week 52, median FVC change was -43.3 ml with inhaled treprostinil and -196.2 ml with placebo. The prespecified clinical-worsening outcome included the first occurrence of death from any cause, hospitalization for a respiratory cause, or a relative decline of at least 10% in percentage predicted FVC. In the time-to-event analysis, that outcome occurred in 31.8% of patients receiving treprostinil and 44.5% of those receiving placebo. The reported hazard ratio was 0.67, with a 95% confidence interval of 0.52 to 0.88 and P=0.003. No significant difference was seen in time to IPF exacerbation, and no further inferences were made regarding secondary end points.

On tolerability, cough was the most frequent adverse event, occurring in 54.8% of patients assigned to treprostinil and 33.1% of those assigned to placebo. Discontinuation occurred in 40.5% and 32.8%, respectively. Adverse events were the primary reason for stopping therapy in 20.7% of treprostinil-treated patients and 14.7% of placebo-treated patients. Investigators also noted that efficacy and safety outcomes were similar in analyses of the combined trial data from both studies. Across 52 weeks, smaller FVC decline and fewer clinical-worsening events were paired with more cough and more treatment discontinuation.