FDA Approves Treprostinil Inhalation Powder for PAH and PH-ILD

The FDA approved an inhalation powder formulation of treprostinil (formerly LIQ861, Yutrepia; Liquidia Corporation) for the treatment of pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD). The approval was supported by findings from the phase 3 INSPIRE trial (NCT03399604).^1,2

Image credit: Pakin | stock.adobe.com

Yutrepia is an investigational, inhaled dry-powder formulation of treprostinil delivered through a low-resistance, palm-sized device. The formulation is intended to be more convenient and accessible for patients. This device is designed using PRIMT technology, which enables the development of drug particles that are both uniform and precise in their size, shape, and composition, and aims to enhance deposition within the lung following oral inhalation. The new drug application was resubmitted on March 28, 2025, which was a complete class 1 response to a previous action letter that was issued on August 16, 2024, granting tentative approval of treprostinil for both PAH and PH-ILD.^1,3,4

“Today, we celebrate for the patients and physicians who will now have access to a potential best-in-class dry-powder form of treprostinil with exceptional portability, tolerability, titratability, and durability,” Roger Jeffs, PhD, CEO of Liquidia, said in a news release. “With today’s milestone, our commercial team is prepared to launch Yutrepia and bring meaningful change to the lives of patients in need, and we look forward to speaking with physicians and patients about the unique benefits of Yutrepia in the days and weeks ahead.”¹

The approval of the nasal powder was based on findings from the phase 3 INSPIRE trial, an open-label, multicenter study to evaluate the long-term safety and tolerability of inhaled treprostinil in patients with PAH aged at least 18 years who transitioned from nebulized treprostinil or added the dry powder formulation. Patients who transitioned from the nebulized treprostinil initiated the powder at a dose comparable to their nebulized treprostinil dose, whereas prostacyclin-naïve patients received 26.5 mcg 4 times a day. Up-titration in 26.5-mcg increments was permitted for both groups.^1,5

The primary safety measures were the incidences of adverse events (AEs) and serious AEs. Exploratory efficacy measures were also assessed during the trial.^1,2,5

A total of 121 patients were enrolled, of whom 29 patients discontinued from the trial, with the most common reason being AEs. The findings showed that 80% of the transition group and 96% of the prostacyclin-naïve group titrated to a dose of 79.5 mcg or greater 4 times per day at day 360, respectively. One patient achieved a dose of 212 mcg 4 times per day.^1,5

“I am so pleased that patients with PAH and PH-ILD now have this newly introduced option for inhaled treprostinil… I am confident in the safety, tolerability and dosing that Yutrepia offers. The low-effort inhalation device used to deliver Yutrepia may make it easier to start and maintain patients on treatment, especially those with limited inspiratory flows or lung capacity,” principal investigator Nicholas Hill, MD, Chief Pulmonary, Critical Care & Sleep Division, professor of medicine at Tufts University School of Medicine, explained.¹

The most common AEs were cough, headache, upper respiratory tract infection, dyspnea, dizziness, throat irritation, diarrhea, chest discomfort, fatigue, and nasopharyngitis. Most of these events were considered treatment-related but mild to moderate in severity and anticipated for prostacyclin therapy administered by inhalation. In an evaluation of exploratory efficacy measures, patients remained stable or improved over the 1-year treatment duration.^1,3,5

“PAH and PH-ILD impact more than 105,000 patients in the U.S. alone. These patient communities and the physicians who serve them need therapies that can lead to the improvement of quality of life,” said Matt Granato, president and CEO of the Pulmonary Hypertension Association. “We are always glad to see industry research leading to the development of drugs that expand options for the patient community.”¹

REFERENCES

1. Liquidia. U.S. FDA Approves Liquidia’s YUTREPIA™ (treprostinil) Inhalation Powder for Patients with Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD). News release. May 23, 2025. Accessed May 27, 2025. https://liquidia.com/news-releases/news-release-details/us-fda-approves-liquidias-yutrepiatm-treprostinil-inhalation

2. Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil (INSPIRE). ClinicalTrials.gov identifier: NCT03399604. Updated July 30, 2024. Accessed May 22, 2025. https://clinicaltrials.gov/study/NCT03399604

3. Liquidia. Liquidia Corporation Announces FDA Acceptance of New Drug Application Resubmission for YUTREPIA™ (treprostinil) Inhalation Powder. News release. March 28, 2925. Accessed May 22, 2025. https://www.liquidia.com/news-releases/news-release-details/liquidia-corporation-announces-fda-acceptance-new-drug

4. Liquidia. Pipeline & Products — Our pipeline. Accessed May 22, 2025. https://liquidia.com/pipeline-and-products

5. Hill NS, Feldman JP, Sahay S, et al. INSPIRE: Safety and tolerability of inhaled Yutrepia (treprostinil) in pulmonary arterial hypertension (PAH). Pulm Circ. 2022; 12:e12119. doi:10.1002/pul2.12119