News|Articles|June 16, 2026

United Therapeutics Plans FDA Submission for Inhaled Treprostinil in IPF

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Key Takeaways

Pooled TETON‑1/2 trials met the primary endpoint, demonstrating significantly less 52‑week FVC loss with inhaled treprostinil than placebo.
Efficacy signals extended to secondary outcomes, reducing clinical worsening and acute IPF exacerbations across both studies.
Benefit was maintained in patients not receiving antifibrotics, while concomitant nintedanib or pirfenidone was associated with even smaller FVC declines.
Adverse events drove discontinuation more often with treprostinil (20.7%) than placebo (14.7%), with cough and headache most frequent.
A planned FDA sNDA by late summer 2026 could position treprostinil as the first inhaled, direct-to-lung pharmacotherapy for IPF.

Pooled TETON trial data showed inhaled treprostinil preserved lung function in IPF, supporting an FDA submission planned for 2026.

United Therapeutics announced that it plans to submit a supplemental New Drug Application to the FDA for nebulized treprostinil (Tyvaso; United Therapeutics), an inhalation treatment for idiopathic pulmonary fibrosis, by the end of summer 2026.¹

The company recently presented pooled analysis from the TETON-1 (NCT04708782) and -2 (NCT05255991) phase 3 trials assessing the safety and efficacy of the inhaled therapy at the American Thoracic Society 2026 International Conference in May, 2026.¹ Both clinical trials met their primary end points of change in vital forced capacity (FVC) at 52 weeks and secondary efficacy end points, including clinical worsening and acute exacerbation of IPF.²Both the FDA and the European Medicines Agency have granted orphan designation for treprostinil to treat IPF; nebulized treprostinil is still investigational.

“The combined analysis provides an incredibly powerful dataset with both studies complementing each other well,” Steven D. Nathan, MD, lead study author on both trials and Schar Chair of the Advanced Lung Disease Program and Lung Transplant Program at Inova Fairfax Hospital, said in a press release.¹ “These findings have the potential to fundamentally impact how we target IPF and manage patients living with this devastating disease.”

Inhaled Treprostinil Preserved Lung Function Across TETON Trials

Across TETON-1 and -2, there were a total of 1191 patients randomized to receive at least 1 dose of treprostinil (n = 597) or the placebo (n = 594). The median change in FVC at 52 weeks was −45.4 ml (95% CI, −73.8 to −23.1) in the treprostinil group and −161.7 ml (95% CI, −194.5 to −134.1) in the placebo group. Among patients not receiving background antifibrotic therapy, the median change in FVC at 52 weeks was −52.6 ml in the treprostinil group and -141.1 ml in the placebo group.²

These data suggest that inhaled treprostinil significantly preserved lung function as a monotherapy, while patients on background therapies, like nintedanib and pirfenidone, experienced even smaller declines in FVC at 52 weeks.

“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,” Nathan said in an interview with The American Journal of Managed Care^®.³

FDA Submission Could Bring First Inhaled Therapy to Patients With IPF

Inhaled treprostinil would be the first inhaled drug approved for IPF, should United Therapeutics’ submission be accepted by the FDA. This treatment addresses a gap in IPF care, targeting direct lung delivery, as the 2 current antifibrotic medications approved for IPF are administered orally.^1,2

Adverse events (AEs) were the primary reason for discontinuation across both trials. Overall, 62 (20.7%) and 44 (14.7%) patients experienced AEs in the treprostinil and placebo groups, respectively.² The most common adverse events were cough, which occurred in 23 (7.7%) vs 3 (1.0%); headache, 9 (3.0%) vs 4 (1.3%); worsening of IPF, 1 (0.3%) vs 8 (2.7%); and acute respiratory failure, 2 (0.7%) vs 6 (2.0%), in the treprostinil and placebo groups, respectively.

“My personal belief is that once this is available in clinical practice and is approved for IPF, the attrition will, in all likelihood, hopefully not be the same because patients now have a drug that they know they're getting, and they know that it works,” Nathan said. “I think the motivation to continue with it will be much greater than it was perhaps in the clinical trial.”³

References

1. United Therapeutics Corporation announces full results of TETON-2 phase 3 clinical trial published in The New England Journal of Medicine. News release. United Therapeutics Investor Relations. March 11, 2026. Accessed June 15, 2026. https://ir.unither.com/press-releases/2026/03-11-2026-221408955

2. Nathan SD, Smith P, Deng C, et al. Phase 3 Trials of Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. N Engl J Med. Published online May 18, 2026. doi:10.1056/NEJMoa2501488

3. McCrear S. Inhaled treprostinil improves FVC in IPF phase 3 trial: Steven D. Nathan, MD. AJMC. April 24, 2026. Accessed June 15, 2026. https://www.ajmc.com/view/inhaled-treprostinil-improves-fvc-in-ipf-phase-3-trial-steven-d-nathan-md