Inhaled Treprostinil After IPF Progression, With Steven Nathan, MD

A post hoc analysis of the phase 3 TETON-2 trial presented at the CHEST 2026 Annual Meeting in Phoenix supports continuing inhaled treprostinil (Tyvaso) after a first disease progression event in patients with idiopathic pulmonary fibrosis (IPF), according to investigator Steven D. Nathan, MD, FCCP, in an interview with HCPLive.¹

The analysis counted every progression event across 52 weeks instead of stopping at the first. In TETON-2, 126 events occurred in 82 patients receiving inhaled treprostinil, compared with 161 events in 115 patients receiving placebo (P =.003).¹ Nathan advised clinicians to focus less on the differences among event types and more on the overall message: continued therapy lowers the likelihood of a clinical progression event, including mortality.

“Yes, you’ve had some evidence of progression, be it decline in lung function or hospitalization, but all the more reason for you to stay on therapy because you’re now at risk of having other progression events,” said Nathan, medical director of Inova’s Advanced Lung Disease Program and Lung Transplant Program and professor of medicine at the University of Virginia.

FVC Decline and Acute Exacerbations in TETON-2

The between-group difference was driven mainly by ≥ 10% relative declines in percent predicted forced vital capacity (FVC; 54 vs 86 events) and concurrent IPF exacerbation with respiratory hospitalization (6 vs 18 events).¹ Adjudicated respiratory hospitalizations were numerically more frequent with inhaled treprostinil (45 vs 34 events).

Nathan attributed the separation in FVC events to the lower threshold for reaching a 10% decline, which allows more patients to meet the endpoint within 52 weeks. He noted multiple studies have linked this degree of decline to worse outcomes. Patients on a declining trajectory also face subsequent events a 52-week study may not capture.

Nathan described acute exacerbations as more meaningful than a 10% FVC decline, citing their mortality and the hospitalizations and supplemental oxygen use often following them.

“It has a lot of ripple effects and ramifications for patient outcomes and is a very patient-centric metric because patients feel it,” Nathan said.

Evidence for Continuing Inhaled Treprostinil After a First Progression Event

Numerically fewer patients receiving inhaled treprostinil had > 1 progression event (26 vs 36), though the comparison did not reach statistical significance (P =.166).¹ Nathan said he is very confident treatment reduces further progression, citing the consistent direction of outcomes across the individual trials and the combined dataset.

Inhaled treprostinil remains investigational for IPF. The FDA has accepted a supplemental New Drug Application based on TETON-1 and TETON-2, with its review expected to be complete in late April 2027, according to United Therapeutics.² Part 1 of this interview covers the analysis design and event-level results.³

Editor’s note: Reported disclosures for Nathan include Boehringer Ingelheim Pharmaceuticals, United Therapeutics Corporation, and more.

References

1. Nathan SD, Cottin V, Flaherty KR, et al. Efficacy of inhaled treprostinil on multiple disease progression events in patients with idiopathic pulmonary fibrosis in the TETON-IPF program. Presented at: CHEST 2026 Annual Meeting; October 20, 2026; Phoenix, AZ.

2. FDA accepts nebulized treprostinil sNDA for idiopathic pulmonary fibrosis. https://www.hcplive.com/view/fda-accepts-nebulized-treprostinil-snda-for-idiopathic-pulmonary-fibrosis. HCPLive. Published September 3, 2026. Accessed November 2, 2026.

3. Nathan S. Inhaled Treprostinil Reduces Recurrent IPF Events, With Steven Nathan, MD. HCPLive. Published October 26, 2026. Accessed November 2, 2026. https://www.hcplive.com/view/inhaled-treprostinil-reduces-recurrent-ipf-events