United Therapeutics Seeks FDA Approval of Tyvaso DPI

United Therapeutics has submitted an application to the U.S. Food and Drug Administration (FDA) seeking approval of Tyvaso DPI, a dry powder inhaled formulation of treprostinil, for both pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD).

To expedite the process, the company  applied for a priority review voucher by the FDA, which could result in a decision by December. Such accelerated reviews shorten the FDA’s consideration of a new drug application to eight months, rather than the standard one year. The agency must first accept the application and issue a formal decision date. It also has yet to approve Tyvaso DPI as trade name.

If approved, breath-powered Tyvaso DPI is expected to be more convenient to take compared with the existing nebulized Tyvaso solution.

The application includes the results of the recently completed BREEZE study (NCT03950739), a Phase 1 clinical trial that demonstrated the safety and tolerability of Tyvaso DPI in people with PAH transitioning from nebulized Tyvaso solution. Improved exercise capacity, reduced patient-reported PAH symptoms and impact, and greater satisfaction with Tyvaso DPI compared to the Tyvaso nebulizer were reported.

Data gathered during a study on pharmacokinetics — the movement of a medicine into, through, and out of the body — in healthy volunteers also was part of the application. Its results showed that Tyvaso DPI led to less treatment exposure variability between participants, suggesting a more precise dosing profile relative to the approved Tyvaso formulation.

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

Tyvaso is a vasodilator that works by relaxing the blood vessels and making them wider, so that blood flows more easily with less pressure. The new product, Tyvaso DPI, combines a dry powder formulation with a small, portable inhalation device called Dreamboat. Developed by MannKind, Dreamboat was approved by the FDA in 2014 for treating diabetes.

Over time, United Therapeutics has developed trepostinil-based therapies for different routes of administration — inhaled (Tyvaso), oral (Orenitram), or infusion/injection (Remodulin) form. Tyvaso is used to improve exercise ability in patients with PAH or PH-ILD.

United Therapeutics and MannKind also are developing BluHale, a Bluetooth-connected accessory for Dreamboat that works with a mobile app intended to track inhaler use.

“Since our founding, we’ve worked hard to ensure our patients have ample choices to deliver treprostinil in various ways to suit their individual needs,” said Gil Golden, MD, PhD, chief medical officer of United Therapeutics. “If approved, Tyvaso DPI will enable patients to go about their day with just a small breath­actuated, dry powder inhaler that easily fits inside a pocket and requires no batteries or external power source to operate.”

Michael Benkowitz, United Therapeutics’ president and chief operating officer added “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.”

“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,” Benkowitz said.