FDA Accepts Priority Review Request for Tyvaso DPI

The U.S. Food and Drug Administration (FDA) has accepted United Therapeutics’ application for a priority review of Tyvaso DPI, an experimental dry powder inhaled formulation of treprostinil, to treat pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD). 

PAH is a condition in which the narrowing of the arteries that connect the heart to the lungs result in high blood pressure. PH-ILD refers to a group of conditions caused by significant scarring (fibrosis) in the lungs, including idiopathic pulmonary fibrosis (IPF). 

When submitting the approval request for Tyvaso DPI — in the form of a new drug application (NDA) — for both indications earlier this year, United also applied for a priority review voucher, which would allow for an expedited eight-month review instead of the typical 12 months. According to the company, the FDA also implied they have not identified any potential review issues at this time, which may enable Tyvaso DPI to be approved for both indications by October. 

“The acceptance of the Tyvaso DPI NDA for review represents an important regulatory step toward offering this meaningful new product to both PAH and PH-ILD patients,” Martine Rothblatt, PhD, chair and CEO of United, said in a press release. 

Tyvaso is a liquid-based inhaled formulation of treprostinil, a medicine known as a vasodilator. It helps expand blood vessels in the lungs, lowering blood pressure. In PH-ILD conditions, lung tissue is thicker and stiff, forming scars. In later stages of the disease, people may develop high blood pressure in lung blood vessels or pulmonary hypertension.

Tyvaso is approved in the U.S. for both PAH and PH-ILD. In addition to Tyvaso, United is marketing an injectable form of treprostinil, called Remodulin, as well as an oral form, called Orenitram.

Tyvaso DPI is a next-generation dry powder form of Tyvaso, delivered by the small portable Dreamboat inhalation device developed by MannKind and approved by the FDA in 2014. United and MannKind also are developing BluHale, an accessory for Tyvaso DPI that can be connected by Bluetooth to a mobile application to help patients track information about inhaler use. 

The NDA includes data from the now completed Phase 1 BREEZE study (NCT03950739), which evaluated the safety and tolerability of Tyvaso DPI over three weeks in PAH patients previously treated with Tyvaso Inhalation Solution.

Of the 51 participants who enrolled, 49 (96%) completed the transition. Most reported adverse side effects were mild-to-moderate and occurred at frequencies similar to those seen in other studies investigating inhaled treprostinil in patients with PAH.

Tyvaso DPI also eased patient-reported symptoms and improved exercise capacity. Participants also reported greater satisfaction with Tyvaso DPI over the nebulizer treatment.

All 49 BREEZE participants who completed the transition elected to enroll in an extension phase to continue treatment with Tyvaso DPI until the study ended, or the therapy became available commercially. 

A pharmacokinetic study in 36 healthy volunteers that investigated how the medicine is absorbed and eliminated from the body, also was included in the NDA. Results showed comparable treprostinil exposure for each corresponding dose of Tyvaso DPI and Tyvaso Inhalation Solution.

There was 50% less variability in the maximum levels of treprostinil and the time it remained in circulation between participants treated with Tyvaso DPI, suggesting a more precise dosing profile for Tyvaso DPI over nebulized Tyvaso. The safety profile for both treatments was consistent. 

Full data from this study will be presented at upcoming conferences and in scientific publications, according to United.

The FDA has indicated the NDA approval will be subject to an inspection of the facility operated by MannKind, where the product is manufactured. According to United, the inspection is expected to be completed in the third quarter of this year. 

“If approved, Tyvaso DPI will represent yet another path to help us achieve our goal of serving 25,000 patients by the end of 2025,” said Rothblatt.