United Therapeutics Announces New England Journal of Medicine Publication of the INCREASE Study Evaluating Tyvaso® in Pulmonary Hypertension Associated with Interstitial Lung Disease
SILVER SPRING, Md. and RESEARCH TRIANGLE PARK, N.C., Jan. 13, 2021 /PRNewswire/ -- United Therapeutics Corporation (Nasdaq: UTHR) today announced that results from the INCREASE clinical study of Tyvaso® (treprostinil) Inhalation Solution for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD) have been published online in the New England Journal of Medicine. Results from INCREASE, the largest and most comprehensive completed study of adult patients with PH-ILD, showed that treatment with inhaled Tyvaso was well tolerated and improved the exercise capacity measure of six-minute walk distance (6MWD) by 31 meters relative to placebo at Week 16 (p<0.001) using the mixed model repeated measurement analysis. Additionally, patients treated with Tyvaso experienced significant improvements in other clinically meaningful outcomes, including a decreased risk of clinical worsening, an improvement in forced vital capacity, and a reduction in exacerbation of underlying lung disease.
Interstitial lung disease (ILD) is a group of lung diseases in which marked scarring occurs within the lungs. It is often complicated by pulmonary hypertension (PH; high blood pressure in the lungs). PH is estimated to affect at least 15% of patients with ILD (approximately 30,000 PH-ILD patients) and may affect up to 86% of patients with more severe ILD. Currently, no therapy is approved by the U.S. Food and Drug Administration (FDA) to treat this serious, life-threatening disease.
"Patients with both interstitial lung disease and pulmonary hypertension are more likely to have a worse course of disease and worse survival rate than patients with interstitial lung disease alone. They often have a very poor quality of life and are significantly limited because of severe shortness of breath despite supplemental oxygen," said Steven D. Nathan, M.D., an INCREASE study investigator and Steering Committee member, Director of the Advanced Lung Disease Program and Director of the Lung Transplant Program at Inova Fairfax Hospital in Falls Church, Va., and Professor of Medicine at Virginia Commonwealth University-Inova Campus. "With no therapies currently approved for PH-ILD, the positive efficacy and notable safety outcomes demonstrated in the INCREASE study are very encouraging. Having an approved inhaled treatment to offer my patients with PH-ILD would be transformational for the medical community and, importantly, for patients living with this disease."
United Therapeutics submitted a supplemental New Drug Application (sNDA) for Tyvaso for the treatment of PH-ILD based on the results of the INCREASE study. The sNDA was accepted by the FDA for review, and the company expects the agency's review to be complete in April 2021.
"We are thrilled that the positive pivotal INCREASE study results were published in such a prestigious journal," said Leigh Peterson, Ph.D., Vice President, Product Development at United Therapeutics. "Based on the final data set from INCREASE, we are confident that Tyvaso will provide clinical benefit to patients with PH-ILD, who are in need of a safe and effective therapy. If approved, Tyvaso will be the first and only therapy approved for the treatment of this serious disease, heralding a significant advance in the way these patients are managed."
INCREASE Study Design and Results
The primary efficacy endpoint was the change in six-minute walk distance (6MWD) measured at peak exposure from baseline to Week 16. Results showed that Tyvaso significantly increased 6MWD by 31 meters as analyzed using the Mixed Model Repeated Measurement (p<0.001). When analyzed using a pre-specified worst case imputation for missing data and Hodges-Lehmann estimate, Tyvaso improved 6MWD by 21 meters relative to placebo over the same time period (p=0.0043). The benefits of Tyvaso were observed across subgroups, including etiology and severity of PH-ILD, age group, gender, baseline hemodynamics, and dose group.
Secondary endpoints included change in plasma concentration of the cardiac biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to Week 16; time to clinical worsening as measured by various metrics including hospitalization due to a cardiopulmonary indication, death (all causes) or lung transplantation; change in peak 6MWD from baseline to Week 12; and change in trough 6MWD from baseline to Week 15. Results showed significant improvements in each of the secondary endpoints:
Treatment with Tyvaso of up to 12 breaths per session, four times daily, was well tolerated. Most treatment-related adverse events were mild to moderate in intensity and included cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea, consistent with the existing Tyvaso label. The safety profile was similar to previous studies of Tyvaso in pulmonary arterial hypertension and known prostacyclin-related adverse events (see the Important Safety Information below under "About Tyvaso").
The webcast will feature members of United Therapeutics' management team, including Michael Benkowitz, President and Chief Operating Officer, and will feature Steven D. Nathan, M.D., an INCREASE study investigator and Steering Committee member, Director of the Advanced Lung Disease Program and Director of the Lung Transplant Program at Inova Fairfax Hospital in Falls Church, Va., and Professor of Medicine at Virginia Commonwealth University-Inova Campus.
Those interested in listening to the webcast can register for the event here or can visit the "Events and Presentations" page at ir.unither.com. A replay of the webcast will be available on the United Therapeutics Investor Relations website after the conclusion of the event.
PH-ILD is estimated to affect at least 15% of patients with ILD (approximately 30,000 PH-ILD patients) and may affect up to 86% of patients with more severe ILD. PH-ILD is included within Group 3 of the World Health Organization (WHO) classification of PH; however, no treatments are approved by the FDA for patients with this disease.
About TYVASO® (treprostinil) Inhalation Solution
TYVASO (treprostinil) is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%).
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.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
DRUG INTERACTIONS/SPECIFIC POPULATIONS
About United Therapeutics
Through our wholly owned subsidiary, Lung Biotechnology PBC, we are focused on addressing the acute national shortage of transplantable lungs and other organs with a variety of technologies that either delay the need for such organs or expand the supply. Lung Biotechnology is the first public benefit corporation subsidiary of a public biotechnology or pharmaceutical company.
TYVASO is a registered trademark of United Therapeutics Corporation.
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SOURCE United Therapeutics Corporation
Company Codes: NASDAQ-NMS:UTHR