In a study published in the New England Journal of Medicine, adults with idiopathic pulmonary fibrosis (IPF) who received inhaled treprostinil for 52 weeks experienced less forced vital capacity (FVC) decline compared to those who received placebo.
Full results of the global, multicenter, double-blind, randomized, placebo-controlled phase 3 TETON-2 trial were detailed in the paper, “Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis.”
“This could be the first inhaled therapy, with direct deposition to the actionable areas, approved for this indication,” said Steven D. Nathan, MD, in Healio. Dr. Nathan is medical director of the advanced lung disease and lung transplant program at Inova Fairfax Hospital in Virginia.
The study included 593 patients with IPF aged 40 or older (71.7 years median age; 80.1% men; 83.8% white; 76.8% of predicted FVC) to determine the efficacy of inhaled treprostinil (Tyvaso) on absolute FVC.
“The foundation of this study emanated from the landmark INCREASE study of Tyvaso in PH-ILD,” Dr. Nathan said. “Spirometry was employed as a safety endpoint in this study, but in actual fact, this safety measure provided a potential efficacy signal as the treatment group had significantly higher FVCs compared to the placebo arm at 16 weeks.”
“Indeed, there is a substantial body of evidence that treprostinil has independent antifibrotic properties. This led to the TETON program, which consists of three trials,” Dr. Nathan added.
TETON-1 consists of patients with IPF in North America, TETON-2 consists of patients with IPF in countries outside of North America and TETON-PPF consists of patients who have progressive pulmonary fibrosis (PPF).
According to the paper, participants in the TETON-2 trial began with three breaths four times daily and increased to the target dose of four breaths four times daily by week four.
At 52 weeks, researchers observed a smaller degree of FVC decline from baseline in patients who received treprostinil compared to patients who received placebo (-49.9mL and -136.4 mL median change, respectively).
Three-fourths of the patients were on background antifibrotic therapy (39.3% pirfenidone; 36.1% nintedanib). When including background antifibrotics in their analysis, researchers observed similar results:
- Patients on nintedanib vs. placebo (median change, -43.4 mL vs. -115 mL)
- Patients on pirfenidone vs. placebo (median change, -52.1 mL vs. 187.6 mL)
- Patients not on background antifibrotics vs. placebo (median change, -54.1 mL vs. -107.1 mL)
Researchers also observed similar outcomes as the main analysis when assessing patients by age, sex, ethnic group and geographic region.
In addition, the treprostinil group had smaller changes than the placebo group in the predicted FVC (median, –1.4 percentage points vs. –3.8 percentage points), the King’s Brief ILD questionnaire total score (–1 point vs. –2.6 points) and the diffusing capacity of the lungs for carbon monoxide (-2.8 percentage points vs. -4.1 percentage points).
“It was great that the study met its primary endpoint, but the magnitude of the difference was a pleasant surprise,” Dr. Nathan said. “What was surprising were the secondary endpoints that were met, including time to clinical worsening, change in the diffusing capacity and, most importantly, improvement in quality of life in comparison to placebo.”
Fewer participants in the treprostinil group compared to placebo experienced “death from any cause, hospitalization due to a respiratory cause or a relative decline of [greater than or equal to] 10% in the percentage of predicted FVC,” (27.2% vs 39%, respectively) the authors wrote.
Between the treprostinil and placebo groups, there was no significant difference in time to first IPF exacerbation (6.4% vs 8.1%) or having at least one serious adverse event (25.2% vs 23.1%). In some cases, adverse events caused patients to discontinue treatment in both groups (16.8% treprostinil; 12.5% placebo). This included death as the adverse event in 10 treprostinil patients and 22 placebo patients.
“My hope is that this trial would open the door for more inhaled antifibrotic therapies to be studied,” Dr. Nathan said.
