In subjects with PAH, transition from Tyvaso® to Tyvaso DPI™ demonstrated safety and tolerability with significant improvements in six-minute walk distance, device preference and satisfaction, and patient reported outcomes

Tyvaso DPI safety confirmed through 51 weeks of optional extension phase data with no study drug-related serious adverse events

FDA action on the New Drug Application for Tyvaso DPI is expected by May 2022

SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)-- United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced the publication of additional clinical and long-term safety data from the BREEZE study evaluating Tyvaso DPI™ (treprostinil) in patients with pulmonary arterial hypertension (PAH) in the journal Pulmonary Circulation.

The publication evaluated the BREEZE study and its ongoing optional extension phase (OEP), and concluded:

• Tyvaso DPI’s delivery device, along with the clinical results from BREEZE, may facilitate the introduction of inhaled treprostinil earlier in the clinical course of PAH for appropriate patients;

• Doses of Tyvaso DPI above the current recommended dose of nebulized Tyvaso (9-12 breaths four times daily) were well tolerated, potentially allowing for titration to higher dose levels without resulting in prolonged treatment sessions;

• A simplified dosing regimen could potentially increase patient compliance; and

• Tyvaso DPI has a pharmacokinetic (PK) profile comparable to nebulized Tyvaso, such that patients will not have to use more drug than nebulized Tyvaso to get the same treprostinil blood concentration or treatment effect.

Tyvaso DPI is a next-generation dry powder formulation of Tyvaso, which is currently undergoing review by the U.S. Food and Drug Administration (FDA). If approved, Tyvaso DPI is expected to provide a more convenient method of administration as compared with traditional nebulized Tyvaso therapy.

“If approved, I believe Tyvaso DPI could represent a very exciting addition to the treatment paradigm for the PAH population,” said Leslie Spikes, M.D., Associate Professor of Pulmonary and Critical Care Medicine at the University of Kansas Medical Center. “The ease of use, portability, and ability to titrate the dose with Tyvaso DPI should have a beneficial impact on patient compliance and persistence and could result in improved exercise ability.”

“We’re thrilled that this manuscript builds on earlier data presented at the European Respiratory Society’s 2021 International Congress, with additional long-term follow-up data that continues to show a strong safety profile for patients transitioning from nebulized Tyvaso to Tyvaso DPI,” said Peter Smith, PharmD, Vice President, Product Development, at United Therapeutics. “The optional extension phase is still ongoing, and we’ve accrued over 71 patient-years of experience with Tyvaso DPI.”

The BREEZE study

The BREEZE study enrolled 51 subjects on a stable regimen of Tyvaso who were transitioned to Tyvaso DPI at a corresponding treprostinil dose. The primary objective of the study was to evaluate the safety and tolerability of Tyvaso DPI during a three-week treatment phase in PAH patients previously treated with Tyvaso Inhalation Solution; the majority of patients in the study were on dual background PAH therapies.

Top line data showing the BREEZE study met its primary objective were released in January 2021 and clinical data was presented at the European Respiratory Society International Congress in September 2021.

Secondary objectives of the study included changes in six-minute walk distance (6MWD), device preference and satisfaction as evaluated through the Preference Questionnaire for Inhaled Treprostinil Devices (PQ-ITD), and patient reported PAH symptoms and impact (PAH-SYMPACT®).

Primary safety and tolerability objective. Transition from Tyvaso to Tyvaso DPI demonstrated safety and tolerance. Forty-nine out of 51 patients (96%) completed the three-week treatment phase, while two subjects discontinued due to treatment-related adverse events during the treatment phase. There were no study drug-related serious adverse events. Most adverse events experienced during the study were mild to moderate in severity and occurred at severities and frequencies consistent with those seen in other inhaled treprostinil studies in patients with PAH. Please see Important Safety Information about Tyvaso at the end of this press release.

Secondary objectives. Three weeks after switching from Tyvaso to Tyvaso DPI, patients in the BREEZE study demonstrated:

• Significant improvements in 6MWD compared to baseline. Improvements of 11.5 meters (p=0.0217) in 6MWD compared to baseline were observed through the three-week treatment phase;

• Significant improvements in overall satisfaction with the Tyvaso DPI inhaler. Using the PQ-ITD, significant improvements (p