Inhaled Treprostinil Improves FVC in IPF TETON-1 Trial: Steven D. Nathan, MD

Recent results from the TETON-1 phase 3 clinical trial assessing inhaled treprostinil to treat idiopathic pulmonary fibrosis (IPF) showed a significant change in forced vital capacity (FVC) compared with placebo.¹

Beyond meeting the study’s primary end points of change in absolute FVC, treprostinil also significantly reduced the risk of clinical worsening in addition to various other improvements. This therapy shows promise as a direct therapy and a promising cornerstone of future combination therapies for IPF, lead study author Steven D. Nathan, MD, medical director of the Advanced Lung Disease Program and Lung Transplant Program at Inova Fairfax Hospital, said in an interview with The American Journal of Managed Care^® (AJMC^®).

In this Q&A, Nathan dissects the study’s findings and the future application for patients with IPF.

This transcript has been lightly edited for clarity.

AJMC: What were the most common adverse events observed, and how do they compare to existing IPF therapies like nintedanib or pirfenidone in terms of tolerability?

Nathan: The main one was cough, and then treprostinil is a prostanoid, so there was some flushing, a little bit of headache, and a little bit of gastrointestinal (GI) upset because there is some systemic absorption.

But the biggest issue was the cough that we spoke about previously. All the antifibrotics have tolerability issues. Certainly, pirfenidone does in terms of GI side effects and photosensitivity. Nintedanib has the main side effect of diarrhea, and a lot of the attrition on that drug is due to uncontrolled diarrhea.

And then we have the new kid on the block, which is nerandomilast, which also has some of these same side effects, including diarrhea, but generally is much better tolerated than the other antifibrotics.

AJMC: Treprostinil’s mechanism differs from antifibrotics currently used in IPF. Based on your findings, do you see evidence that it may be targeting different aspects of disease biology?

Nathan: I think it certainly is. It was initially approved as a pulmonary vasodilator in pulmonary arterial hypertension and subsequently approved in pulmonary hypertension and interstitial lung disease. But I do believe in this a lot, especially the biological plausibility as to why it has independent antifibrotic properties.

It's not just working on the vasculature, but it's working at the alveoli interface in terms of having direct antifibrotic properties through the process gland and process cycling pathways.

AJMC: How do these results shape the future treatment landscape for IPF, and what are the next steps? Are treatments like treprostinil moving toward broader approvals or additional confirmatory trials?

Nathan: I think we have the confirmatory trial in the TETON-1 study, and now we have 2 pivotal phase 3 studies, which is typically what the FDA will require in order to garner an approval. I think we have the data to get through the FDA. I don't want to preempt, but I think it should become available as another treatment for IPF, which will give us our fourth antifibrotic to treat these patients. And I think having choice is great for providers and especially for patients, and I think it will have a firm place in current treatment management of patients with IPF.

It should be the first inhaled drug approved for IPF. It's a little bit different compared to the systemic drugs, and I think, intuitively, to me, it makes a lot of sense to give something inhaled where you can get direct deposition in the areas that it needs to get vs giving something systemically. And I think what I foresee for the future, as we've seen in many disease states, is combination therapy in many of our patients, and this might be one of the cornerstones of combination therapy.

Reference

1. Nathan SD, Smith P, Deng C, et al. Inhaled treprostinil for idiopathic pulmonary fibrosis. N Engl J Med. Published online March 11, 2026. doi:10.1056/NEJMoa2512911