United Therapeutics Asks FDA to Approve Tyvaso DPI

United Therapeutics has submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) requesting the approval of Tyvaso DPI, an investigational dry powder inhaled formulation of treprostinil, to treat pulmonary hypertension associated with interstitial lung disease (PH-ILD). 

PH-ILD is an umbrella term for lung fibrotic-related conditions, including idiopathic pulmonary fibrosis (IPF).

With this application, the company also is seeking the approval of Tyvaso DPI for the treatment of pulmonary arterial hypertension (PAH), a condition in which the arteries connecting the heart to the lungs become increasingly narrower, resulting in high blood pressure.

United Therapeutics also has applied a priority review voucher to the NDA for an expedited eight-month review, instead of the standard 12-month review. According to the company, this expedited review might enable Tyvaso DPI to be approved for both indications by the end of the year. 

“We’re excited for the potential for Tyvaso DPI to be one of our next product launches, assuming a timely approval in December of this year,” Michael Benkowitz, president and chief operating officer of United Therapeutics, said in a press release.

“The patient choice afforded by Tyvaso DPI, if approved, will help us achieve our goal of doubling the number of patients on Tyvaso therapy by the end of 2022. We remain committed to investigating, innovating, and delivering multiple therapies and treatments designed to help our patients manage their conditions,” he said. 

PH-ILD conditions such as IPF are characterized by the thickening and stiffening of lung tissue that leads to the formation of scars (fibrosis). People with late-stage disease also may develop pulmonary hypertension, or high blood pressure, in lung blood vessels.

Tyvaso is a solution-based inhaled formulation of treprostinil, a vasodilator that helps widen blood vessels in the lungs to lower blood pressure. Recently, it became the first treatment approved in the U.S. for people with PH-ILD. It also is approved to treat PAH.

In addition to being available in an inhaled solution form, treprostinil is marketed in an oral form called Orenitram, and in an injectable form known as Remodulin (all marketed by United Therapeutics).

Tyvaso DPI is a dry powder formulation of treprostinil that delivers the medicine using the small, portable Dreamboat inhalation device developed by MannKind, which was approved by the FDA in 2014.

The NDA was supported by data from the recently completed Phase 1 BREEZE trial (NCT03950739), which evaluated the safety, effectiveness, and pharmacological properties of Tyvaso DPI in 51 people with PAH who  previously were on a stable regimen of Tyvaso Inhalation Solution.

Overall, 49 participants (96%) completed the treatment, and after three weeks, patients showed improved exercise capacity, reduced patient-reported symptoms, and greater satisfaction with the Tyvaso DPI treatment relative to their previous nebulizer treatment regimen.

All participants who completed the three-week treatment enrolled in an extension phase to continue receiving Tyvaso DPI until the study ended or the therapy became available commercially. According to United Therapeutics, improvements seen in exercise capacity also were sustained in the extension phase of the study.

The NDA was supported by data from a study involving 36 healthy volunteers, which aimed to assess the pharmacokinetics (how the medicine moves into and through the body) of three dose levels of the investigational medication. 

This study demonstrated that exposure to treprostinil was comparable between Tyvaso DPI and Tyvaso Inhaled Solution for each dose level. Yet, the lower variability on treprostinil concentrations between subjects treated with Tyvaso DPI suggested the dry powder formulation allowed for more precise dosing relative to the nebulizer form.

“In the BREEZE and pharmacokinetic studies, Tyvaso DPI demonstrated safety, tolerability, and a comparable pharmacokinetic profile to nebulized Tyvaso Inhalation Solution,” said Leigh Peterson, PhD, senior vice president at United Therapeutics. “If approved by the FDA, we expect Tyvaso DPI will provide an advancement in the delivery of inhaled treprostinil therapy.”