United Therapeutics Highlights Poster Presentations from the Recent CHEST 2020 Meeting

Clinical study data suggests Tyvaso® improved forced vital capacity, an important measure of lung function, in patients with pulmonary hypertension associated with interstitial lung disease

Seven poster presentations are available at ir.unither.com

SILVER SPRING, Md. and RESEARCH TRIANGLE PARK, N.C., Oct. 22, 2020 /PRNewswire/ -- United Therapeutics Corporation (Nasdaq: UTHR) today announced new clinical data on Tyvaso® (treprostinil) Inhalation Solution in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD) at CHEST 2020, the annual meeting of the American College of Chest Physicians, held October 18-21. The presentation featured safety data from the phase 3 INCREASE study of Tyvaso, which showed that patients with PH-ILD receiving Tyvaso, compared to those receiving placebo, experienced fewer exacerbations of underlying lung disease and an improvement in forced vital capacity (FVC). The data were featured in one of seven abstracts sponsored by United Therapeutics at the conference.

Interstitial lung disease (ILD) is a group of lung diseases in which significant scarring occurs within the lungs. It is often complicated by pulmonary hypertension (PH; high blood pressure in the lungs). PH-ILD is estimated to affect 30,000 people in the United States. Currently, no drug therapy is approved by the U.S. Food and Drug Administration (FDA) to treat this serious and potentially life-threatening disease.

"Patients with both interstitial lung disease and pulmonary hypertension face severe difficulty breathing which often requires supplemental oxygen and substantially compromises patients' quality of life," said Gil Golden, M.D., Ph.D., Chief Medical Officer of United Therapeutics. "Yet, no therapies are currently approved to treat the condition." 

"We are encouraged by the favorable impact on lung function in PH-ILD patients receiving Tyvaso versus placebo in the INCREASE study, as well as preclinical evidence demonstrating the antifibrotic activity of treprostinil," said Leigh Peterson, Ph.D., Vice President of Product Development at United Therapeutics. "These findings are the basis of additional studies we are planning to assess Tyvaso in treating various forms of interstitial lung disease. We look forward to launching our phase 3 TETON clinical program next year; the first study in this program will enroll subjects with idiopathic pulmonary fibrosis."

The research, The Impact of Inhaled Treprostinil on Patient Lung Function: Results from the INCREASE Study, was presented by Aaron Waxman, M.D., Ph.D., Director of the Pulmonary Vascular Disease Program at Brigham and Women's Hospital and the chair of the INCREASE Study Steering Committee, and provides further detail regarding Tyvaso's effects on FVC during the course of the study. The phase 3, multicenter, randomized, double-blind, placebo-controlled, 16-week, parallel group INCREASE study evaluated Tyvaso in adult patients suffering from World Health Organization (WHO) Group 3 PH-ILD. A total of 326 patients were enrolled at 93 centers and randomized to inhaled Tyvaso (n=163) four times daily or placebo (n=163). United Therapeutics previously announced top-line data from INCREASE showing it met all primary and secondary endpoints and the submission of a supplemental NDA which is currently under review by the FDA.

To evaluate lung function, pulmonary function testing (PFT) was conducted as a safety assessment at Study Weeks 8 and 16. Exacerbation of underlying lung disease, defined as an acute, clinically significant, respiratory deterioration accompanied by evidence of new widespread alveolar abnormality, was assessed over the course of the study and by each Principal Investigator.

Patients receiving Tyvaso, compared to those receiving placebo, experienced significantly fewer exacerbations of underlying lung disease (43 [26.4%] versus 63 [38.7%]; p=0.02 by Fisher's exact test). Other results include:

• Overall, FVC improved with Tyvaso by 28.47 mL and 44.40 mL at Weeks 8 and 16, respectively, when compared to placebo
• Percent predicted FVC also improved at Weeks 8 (1.79%; p=0.0139) and 16 (1.80%; p=0.0277)
• Subgroup analysis of patients with etiology of idiopathic interstitial pneumonia (IIP) demonstrated FVC improvements of 46.48 mL and 108.18 mL (N=146, p=0.0229) at Weeks 8 and 16, respectively, and improvements in % predicted FVC at Weeks 8 (1.95%, p=0.0373) and 16 (2.88%; p=0.0096) compared to placebo
• Further analysis for patients with etiology of idiopathic pulmonary fibrosis (IPF) demonstrated FVC improvements of 84.52 mL and 168.52 mL (N=92, p=0.0108) at Weeks 8 and 16, respectively, and improvements in % predicted FVC at Weeks 8 (2.54%; p=0.0380) and 16 (3.50%; p=0.0147) compared to placebo

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, many of which are consistent with the existing Tyvaso label. The safety profile was consistent with previous studies of Tyvaso in pulmonary arterial hypertension and known prostacyclin-related adverse events (see the Important Safety Information below under "About Tyvaso").

The poster, entitled "The Impact of Inhaled Treprostinil on Patient Lung Function: Results from the INCREASE Study," is available here.

Other posters presented at CHEST 2020 included:

Title: Low Utilization of Prostacyclin Therapy Prior to Death Among Medicare Patients with Pulmonary Arterial Hypertension Lead Author: Stephen Mathai Available: here

Title: Interim Data from the ADAPT Registry: Patient-Reported Real-World Tolerability and Management of Adverse Events with Oral Treprostinil Lead Author: John Kingrey Available: here

Title: Reasons for Refusing Parenteral Therapy: A Qualitative Study of Patients with Pulmonary Arterial Hypertension Lead Author: Kellie MorlandAvailable: here

Title: Contemporary Dosing Characteristics of Oral Treprostinil in Real-world Clinical Practice in Patients with Pulmonary Arterial Hypertension Lead Author: Karim El-KershAvailable: here

Title: Development of the Pulmonary Hypertension Functional Classification Self-Report (PH-FC-SR)Lead Author: Kristin Highland Available: here

Title: Understanding the Psychological Mindset of People with Pulmonary Arterial Hypertension Lead Author: Lillian HansenAvailable: here

About PH-ILDInterstitial lung disease (ILD) is a group of lung diseases that are characterized by significant scarring or fibrosis of the bronchioles and alveolar sacs within the lungs. Increased fibrotic tissue in ILD prevents oxygenation and free gas exchange between the pulmonary capillaries and alveolar sacs, and the condition can present with a wide range of symptoms, including shortness of breath with activity, labored breathing, and fatigue. Pulmonary hypertension (PH) frequently complicates the course of patients with interstitial lung disease and is associated with worse functional status measured by exercise capacity, greater supplemental oxygen needs, decreased quality of life, and worse outcomes.

An estimated 30,000 patients in the United States may suffer from PH-ILD, which 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

INDICATION

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 FOR TYVASO

WARNINGS AND PRECAUTIONS

• The efficacy of TYVASO has not been established in patients with significant underlying lung disease (such as asthma or chronic obstructive pulmonary disease). Patients with acute pulmonary infections should be carefully monitored to detect any worsening of lung disease and loss of drug effect
• TYVASO is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, TYVASO may cause symptomatic hypotension
• Titrate slowly in patients with hepatic or renal insufficiency, as exposure to treprostinil may be increased in these patients
• TYVASO inhibits platelet aggregation and increases the risk of bleeding
• Co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor gemfibrozil may increase exposure to treprostinil. Co-administration of the CYP2C8 enzyme inducer rifampin may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events, whereas decreased exposure is likely to reduce clinical effectiveness

DRUG INTERACTIONS/SPECIFIC POPULATIONS

• The concomitant use of TYVASO with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension
• Co-administration of the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to oral treprostinil. Co-administration of the CYP2C8 enzyme inducer rifampin decreases exposure to oral treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8
• Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality. There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production
• Safety and effectiveness in pediatric patients have not been established
• It is unknown if geriatric patients respond differently than younger patients. Caution should be used when selecting a dose for geriatric patients

ADVERSE REACTIONS

• The most common adverse reactions seen with TYVASO in ≥4% of PAH patients and more than 3% greater than placebo in the placebo-controlled clinical study were cough (54% vs 29%), headache (41% vs 23%), throat irritation/pharyngolaryngeal pain (25% vs 14%), nausea (19% vs 11%), flushing (15% vs