FDA Accepts United Therapeutics' Supplemental NDA for Nebulized Tyvaso in IPF, With Decision Expected in Late April 2027
Key Insights
The FDA has accepted United Therapeutics' supplemental new drug application for nebulized Tyvaso (treprostinil) in idiopathic pulmonary fibrosis (search), with a target action date in late April 2027.
The filing is supported by the replicate phase 3 TETON-1 and TETON-2 trials, which showed a 111.8 mL between-group difference in FVC change favoring Tyvaso over placebo.
Pooled data showed reduced clinical worsening (29.5% vs 41.8%; HR 0.69) and fewer acute IPF exacerbations (3.2% vs 6.1%; HR 0.52) with nebulized Tyvaso.
The FDA has accepted United Therapeutics' supplemental new drug application for nebulized Tyvaso Inhalation Solution for the treatment of idiopathic pulmonary fibrosis (search) (IPF), the company announced on September 2. The agency's acceptance is a procedural step indicating the filing is complete enough to review, not a verdict on approvability; United Therapeutics expects the review to be completed in late April 2027, and the FDA could approve the drug, request additional information, or decline to approve it. Nebulized Tyvaso remains investigational for IPF and is not approved for that use.
A First-in-Class Ambition in a Disease With Few Options
Tyvaso, an inhaled formulation of treprostinil, is already approved for pulmonary arterial hypertension (search) and for pulmonary hypertension associated with interstitial lung disease. United Therapeutics estimates that at least 100,000 people in the United States are living with IPF, a disease with few treatment options.
"Current FDA-approved treatments for IPF are oral antifibrotic therapies," Franck Rahaghi, MD, chief medical officer of United Therapeutics, told Healio. "If approved, nebulized Tyvaso (treprostinil) would be the first and only inhaled antifibrotic treatment for IPF, combining direct lung delivery with multi-modal activity across fibrotic, vascular and inflammatory pathways."
IPF causes progressive scarring of the lungs from an unknown cause, gradually reducing the lungs' ability to move oxygen into the blood and ultimately leading to respiratory failure. It rarely appears before age 50 and can be associated with cigarette smoking and certain genetic factors, according to the company. Acid reflux, some viral infections, air pollution, and workplace exposures may also be risk factors. Both the FDA and the European Medicines Agency (search) have granted treprostinil orphan designation for IPF.
The IPF program originated from an earlier trial called INCREASE in patients with pulmonary hypertension and interstitial lung disease. A post-hoc analysis of that study suggested the drug was associated with improved lung function, prompting the company to launch the TETON trials.
TETON-1 and TETON-2 Data Underpinning the Filing
The supplemental application includes data from the replicate, multisite, double-blind, randomized, placebo-controlled phase 3 TETON-1 and TETON-2 trials, each running 52 weeks. TETON-1 enrolled patients in the United States and Canada, while TETON-2 enrolled patients outside North America. Data from TETON-2 were published in The New England Journal of Medicine in March, while TETON-1 data plus pooled trial data were simultaneously presented at the American Thoracic Society International Conference and published in The New England Journal of Medicine in May.
In the pooled population, researchers found a smaller degree of FVC decline between baseline and week 52 among adult patients with IPF receiving nebulized Tyvaso versus placebo (median change, −45.4 mL vs. −161.7 mL; between-group difference, 111.8 mL; 95% CI, 79.7-144.1; P < .0001). The pattern persisted across background therapy subgroups: patients on nintedanib (median change, −37.9 mL vs. −130.4 mL; P < .0001), patients on pirfenidone (−46.7 mL vs. −217.4 mL; P < .0001), and patients not on any background antifibrotic therapy (−52.6 mL vs. −141.1 mL; P = .0387).
For clinical worsening, a smaller proportion of patients receiving nebulized Tyvaso versus placebo experienced death from any cause, respiratory-related hospitalization, or a relative decline of at least 10% in percent-predicted FVC (29.5% vs. 41.8%), corresponding to a significantly lower risk for the composite outcome (HR = 0.69; 95% CI, 0.57-0.84). Time to first acute IPF exacerbation in the pooled dataset also differed significantly between groups (3.2% vs. 6.1%; HR = 0.52; 95% CI, 0.3-0.91).
"In the TETON clinical program, nebulized Tyvaso significantly improved preservation of lung function and reduced the risk of clinical worsening and acute IPF exacerbation compared with placebo," Rahaghi told Healio. "These findings highlight the potential for nebulized Tyvaso, if approved for this indication, to meaningfully change the treatment landscape for patients with IPF."
The company reported that the drug also reached statistical significance on most key secondary goals, including changes in a quality-of-life questionnaire and a measure of how well the lungs transfer gas. The trial population was described as broadly treated with background IPF therapy.
Limitations and Safety Considerations
Important limits apply to the evidence. Forced vital capacity measures lung function, not survival, and overall survival at week 52, a secondary endpoint, was not among the results the company listed as statistically significant. The trials were sponsored by United Therapeutics, and TETON-OLE, an open-label extension allowing eligible trial completers to continue treatment, is still evaluating long-term safety.
Safety questions carry over from the drug's existing uses. Tyvaso's prescribing information warns of possible bronchospasm, low blood pressure, and a higher risk of bleeding. In an earlier 12-week trial in pulmonary arterial hypertension (search), cough was reported by 54% of Tyvaso patients compared with 29% on placebo, and headache by 41% compared with 23%. Because IPF mainly affects older adults, many patients already take other medications; the prescribing information warns that using Tyvaso with diuretics, blood pressure drugs, or other vasodilators may increase the risk of symptomatic low blood pressure, making a full medication review relevant for anyone considering it.
What the Review Means for Patients and the Pipeline
Nothing changes for IPF patients today. People taking an oral antifibrotic should not stop or change treatment because of this review, and anyone curious about inhaled treprostinil should discuss it with a pulmonologist. Insurance coverage for an unapproved use can be difficult to obtain, so an FDA decision may matter for access as much as for prescribing. Nebulized Tyvaso is given with a dedicated inhalation device, so patients who eventually use it would need training on the system.
United Therapeutics said in its TETON-PPF enrollment update that enrollment is complete in its study of the drug in progressive pulmonary fibrosis (search), a related condition the company says affects about 200,000 Americans, with topline results expected in the second half of 2027.
Open questions remain, including how the FDA will weigh the lung function data, what long-term safety looks like in IPF, and what the drug would cost for this use. The next milestone is the agency's decision, which United Therapeutics expects in late April 2027.