SILVER SPRING, Maryland, RESEARCH TRIANGLE PARK, North Carolina
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April 25, 2022
(press release)
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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 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: Pharmacokinetic results. Systemic exposure between the nebulized Tyvaso and Tyvaso DPI was comparable between the two formulations. Between-subject variability for area under the curve (AUC) and peak serum concentration (Cmax) parameters was similar across dose levels for each formulation (Tyvaso or Tyvaso DPI). However, variability of AUC and Cmax was 2- to 3-fold lower for Tyvaso DPI when compared to Tyvaso. Optional extension phase. Subjects in BREEZE were given the opportunity to continue in an OEP. All subjects who completed the treatment phase (49/51) elected to continue in the OEP. At the July 2021 data cutoff for this manuscript, 17 patients had reached 51 weeks of Tyvaso DPI use and 39 patients were still participating in the OEP, but not all patients had reached the 51-week visit at the cut-off. Additional data from the OEP also demonstrated: The manuscript, entitled “BREEZE: Open-label Clinical Study to Evaluate the Safety and Tolerability of Treprostinil Inhalation Powder as Tyvaso DPI in Patients With Pulmonary Arterial Hypertension,” is available on the Pulmonary Circulation Journal website and at https://doi.org/10.1002/pul2.12063. About PAH Also known as World Health Organization Group 1 Pulmonary Hypertension, PAH is life-threatening high blood pressure in the arteries of the lungs, affecting the ability of the heart and lungs to work properly in afflicted patients. PAH is a serious, progressive disease for which there is no known cure. About Tyvaso DPI Tyvaso DPI is an investigational drug-device combination therapy comprised of a dry powder formulation of treprostinil and a small, portable, dry powder inhaler. If approved, Tyvaso DPI is expected to provide a more convenient method of administration compared with traditional nebulized Tyvaso therapy. United Therapeutics has developed Tyvaso DPI under a collaboration and license agreement with MannKind Corporation (Nasdaq: MNKD). United Therapeutics and MannKind are also developing BluHale®, a Bluetooth-connected accessory for the Tyvaso DPI inhaler with a companion mobile application intended to help the patient track information about inhaler use. United Therapeutics has submitted a New Drug Application (NDA) to the FDA seeking approval of Tyvaso DPI to treat adult patients with PAH and pulmonary hypertension associated with interstitial lung disease. FDA action on the NDA is anticipated by May 2022. About TYVASO (treprostinil) Inhalation Solution INDICATION TYVASO (treprostinil) is a prostacyclin mimetic indicated for the treatment of: IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS DRUG INTERACTIONS/SPECIFIC POPULATIONS ADVERSE REACTIONS Please see Full Prescribing Information, the TD-100 and TD-300 TYVASO® Inhalation System Instructions for Use manuals, and other additional information at www.tyvaso.com or call 1‑877‑UNITHER (1-877-864-8437). United Therapeutics: Enabling Inspiration We build on the strength of our research and development expertise and a distinctive, entrepreneurial culture that encourages diversity, innovation, creativity, sustainability, and, simply, fun. Since inception, our mission has been to find a cure for pulmonary arterial hypertension and other life-threatening diseases. Toward this goal we have successfully gained FDA approval for five medicines, we are always conducting new clinical trials, and we are working to create an unlimited supply of manufactured organs for transplantation. We are the first publicly-traded biotech or pharmaceutical company to take the form of a public benefit corporation (PBC). Our public benefit purpose is to provide a brighter future for patients through (a) the development of novel pharmaceutical therapies; and (b) technologies that expand the availability of transplantable organs. At the same time, we seek to provide our shareholders with superior financial performance and our communities with earth-sensitive energy utilization. You can learn more about what it means to be a PBC here: unither.com/PBC. Forward-looking Statements Statements included in this press release that are not historical in nature are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, statements relating to our pending NDA for Tyvaso DPI, the timing of its potential approval, the potential clinical benefits of Tyvaso DPI if and when it is approved by the FDA, our ability to create value and sustain our success in the long-term, as well as our efforts to develop technologies that either delay the need for transplantable organs or expand the supply of transplantable organs. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, that could cause actual results to differ materially from anticipated results. Consequently, such forward-looking statements are qualified by the cautionary statements, cautionary language and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of April 6, 2022 and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events, or any other reason. TYVASO is a registered trademark of United Therapeutics Corporation. TYVASO DPI is a trademark of United Therapeutics Corporation. BLUHALE is a registered trademark of MannKind Corporation. PAH-SYMPACT is a registered trademark of Actelion Pharmaceuticals Ltd société anonyme. Dewey Steadman at (202) 919-4097 Source: United Therapeutics Corporation
The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities.
While there are long-term data on use of treprostinil by other routes of administration, nearly all controlled clinical experience with inhaled treprostinil has been on a background of bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase type 5 inhibitor). The controlled clinical experience was limited to 12 weeks in duration.
In a 12-week, placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most common adverse reactions seen with TYVASO in ≥4% of PAH patients and more than 3% greater than placebo in the placebo-controlled study were cough (54% vs 29%), headache (41% vs 23%), throat irritation/pharyngolaryngeal pain (25% vs 14%), nausea (19% vs 11%), flushing (15% vs <1%), and syncope (6% vs <1%). In addition, adverse reactions occurring in ≥4% of patients were dizziness and diarrhea.
In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions were similar to the experience in studies of PAH.
Email: ir@unither.com
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