Inhaled Treprostinil Slows FVC Decline in IPF, Study Shows

A new study published in The New England Journal of Medicine offers a promising development for individuals living with idiopathic pulmonary fibrosis (IPF), a chronic and progressive lung disease. Results from the phase 3 TETON-2 trial indicate that inhaled treprostinil, administered over 52 weeks, slowed the decline in forced vital capacity (FVC)—a key measure of lung function—compared to placebo. This finding suggests a potential new therapeutic option for managing IPF, a condition with limited treatment choices and a generally poor prognosis.

Understanding Idiopathic Pulmonary Fibrosis and FVC

IPF is a devastating lung disease characterized by the scarring and thickening of lung tissue, leading to shortness of breath and a gradual loss of lung function. The disease affects approximately 50,000 to 150,000 Americans, and its cause remains largely unknown. The American Thoracic Society provides comprehensive information on IPF, its diagnosis, and management.

FVC, or forced vital capacity, is a measurement of the total amount of air a person can forcibly exhale after a deep breath. In IPF, FVC typically declines over time as lung tissue becomes increasingly scarred and less flexible. Slowing the rate of FVC decline is a primary goal of treatment, as it can help to preserve lung function and improve quality of life.

TETON-2 Trial: Design and Key Findings

The TETON-2 trial, led by Steven D. Nathan, MD, of Inova Fairfax Hospital, involved 593 adults with IPF across multiple centers outside of North America. Participants were randomly assigned to receive either inhaled treprostinil or a placebo for 52 weeks. The study’s primary endpoint was the change in FVC from baseline to week 52.

Researchers found that the median decline in FVC was significantly smaller in the treprostinil group (-49.9 mL) compared to the placebo group (-136.4 mL). This difference of 95.6 mL was statistically significant (P < .001), indicating that inhaled treprostinil demonstrably slowed the rate of lung function decline. Notably, the majority of patients (75.4%) were already receiving background therapy with either pirfenidone or nintedanib, two other antifibrotic medications currently approved for IPF. The benefit of treprostinil was observed regardless of whether patients were on these background therapies.

Beyond FVC: Clinical Worsening and Quality of Life

In addition to the improvement in FVC decline, the study also showed a reduction in clinical worsening events among patients receiving treprostinil. A clinical worsening event was defined as death from any cause, hospitalization due to a respiratory cause, or a 10% or greater relative decline in FVC. 27.2% of patients in the treprostinil group experienced a clinical worsening event, compared to 39% in the placebo group, representing a 30% reduction in risk (HR = 0.71; 95% CI, 0.53-0.95).

patients treated with inhaled treprostinil reported improvements in quality of life, as measured by the King’s Brief ILD questionnaire, and showed a smaller decline in diffusing capacity of the lungs for carbon monoxide (DLCO), another important measure of lung function. These findings suggest that inhaled treprostinil may offer benefits beyond simply slowing FVC decline, potentially improving overall well-being for individuals with IPF.

How Does Inhaled Treprostinil Work?

Treprostinil is a prostacyclin analog, a type of medication that widens blood vessels and reduces pulmonary artery pressure. While initially approved for pulmonary hypertension, research has suggested that treprostinil may also possess antifibrotic properties, meaning it could help to slow the scarring process in the lungs. Previous studies, such as the INCREASE trial, demonstrated improvements in lung function with inhaled treprostinil in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD), prompting further investigation into its potential role in IPF.

Dr. Nathan explained that the foundation for this study stemmed from observations made during the INCREASE trial, where improvements in spirometry (a lung function test) suggested a potential efficacy signal. He also highlighted the growing body of evidence supporting treprostinil’s independent antifibrotic effects, leading to the launch of the TETON program, which includes three ongoing trials evaluating treprostinil in various fibrotic lung diseases.

Safety and Tolerability

The TETON-2 trial also assessed the safety and tolerability of inhaled treprostinil. Adverse events were reported in 91.6% of patients in the treprostinil group and 89.5% in the placebo group, with similar proportions experiencing serious adverse events. The most common adverse event was cough, reported in nearly half of the treprostinil group (48.3%) compared to a quarter of the placebo group (24.1%). However, severe cough was uncommon, occurring in only two patients in the treprostinil group.

A slightly higher proportion of patients discontinued treatment in the treprostinil group (33.6%) compared to the placebo group (24.7%), with adverse events being a common reason for discontinuation. Deaths occurred in 3.4% of the treprostinil group and 7.5% of the placebo group.

What’s Next for IPF Treatment?

The results of the TETON-2 trial are encouraging and suggest that inhaled treprostinil could become a valuable addition to the treatment armamentarium for IPF. The U.S. Food and Drug Administration (FDA) is currently reviewing the data, and a decision on approval is expected in the coming months. If approved, treprostinil would be the fourth approved antifibrotic therapy for IPF, offering clinicians and patients more options for managing this challenging disease.

Dr. Nathan expressed hope that this trial will pave the way for further research into inhaled antifibrotic therapies. The TETON-1 study, focusing on patients in North America, is still ongoing, and the TETON-PPF trial is evaluating treprostinil in patients with progressive pulmonary fibrosis. These studies will provide further insights into the potential benefits of inhaled treprostinil and its role in the broader landscape of IPF treatment.

For more information about IPF and current treatment options, patients and healthcare professionals can consult resources from the Pulmonary Fibrosis Foundation and the New England Journal of Medicine publication of the TETON-2 trial results.