United Therapeutics to Feature Clinical Data Across its Commercial and Development Portfolio at the CHEST 2022 Annual Meeting

Data from the INCREASE open label extension study of Tyvaso^® detail its long-term safety and tolerability in pulmonary hypertension associated with interstitial lung disease

Data from the FREEDOM-EV open label extension study of Orenitram^® details an association with improved survival and, separately, its effects as part of a combination therapy regimen in patients with pulmonary arterial hypertension

Real-world analysis to describe initial combination treatment strategies in pulmonary arterial hypertension

United Therapeutics is sponsoring the CHEST Women & Pulmonary Luncheon and hosting a PH-ILD educational symposium

United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced that three presentations and two posters across its commercial and development portfolio will be presented at the CHEST 2022 Annual Meeting hosted by the American College of Chest Physicians taking place October 16-19, 2022, in Nashville, Tennessee. In addition, United Therapeutics is sponsoring the CHEST Women & Pulmonary Luncheon and will host an educational symposium on pulmonary hypertension associated with interstitial lung disease (PH-ILD), both on Monday, October 17, 2022.

“CHEST 2022 will provide us with the opportunity to update the pulmonology and pulmonary hypertension communities on long-term data from the INCREASE and FREEDOM-EV open-label extension studies, and to present a concerning real-world claims data analysis describing a potential gap in optimal initial combination therapy for pulmonary arterial hypertension patients,” said Andrew Nelsen, Pharm.D., Vice President, Global Medical Affairs at United Therapeutics. “We’re also thrilled to sponsor two important events at this congress: the Women & Pulmonary Luncheon where women in chest medicine can gain insights on how to advance their careers in this critically important field, and a symposium detailing the screening-to-diagnosis-to-early treatment journey for PH-ILD.”

Oral Presentations include:

Rapid fire original investigation presentation, Monday, October 17, 12:23 - 12:27 PM CT: Rapid Area 1B/4104 – Oral Treprostinil as Part of a Triple-Therapy Regimen for Pulmonary Arterial Hypertension: Analysis from the FREEDOM-EV Open-Label Extension. Presented by Jean Elwing, M.D., FCCP, University of Cincinnati.

Rapid fire original investigation presentation, Monday, October 17, 12:43 - 12:47 PM CT: Rapid Area 1B/4104 – Initial Treatment Strategy in Patients with Pulmonary Arterial Hypertension Using Two Large US Administrative Claims Databases. Presented by Sandeep Sahay, M.D., FCCP, Houston Methodist Hospital.

Rapid fire original investigation presentation, Wednesday, October 19, 11:31 - 11:35 AM CT: Rapid Area 2A/4142 – The Burden of Illness in Patients with Pulmonary Hypertension due to Chronic Obstructive Pulmonary Disease in US Administrative Claims Data. Presented by James Klinger, M.D., FCCP, Alpert Medical School of Brown University.

Posters include:

Pulmonary arterial hypertension (PAH) abstract poster, Tuesday, October 18, 1:30 - 2:30 PM CT: 4218/2070 – Long-Term Safety and Tolerability of Inhaled Treprostinil in Patients with Pulmonary Hypertension Associated with Interstitial Lung Disease in the INCREASE Open-Label Extension. Presented by Jean Elwing, M.D., FCCP, University of Cincinnati.

PAH abstract poster, Tuesday, October 18, 1:30 - 2:30 PM CT: 4218/2071 – Oral Treprostinil Treatment is Associated with Improved Survival in Pulmonary Arterial Hypertension Participants in FREEDOM-EV and the FREEDOM-EV Open-Label Extension Study. Presented by R. James White, M.D., Ph.D., University of Rochester.

Sponsored events include:

The CHEST 2022 Women & Pulmonary Luncheon, Monday, October 17, 12:00 - 1:30 PM CT, featuring Janet Bickel, a noted career and leadership development coach who will provide tips on how to advance one’s career through her presentation, “You Are the CEO of Your Own Career.” The luncheon will be held at the Music City Convention Center, Karl Dean Grand Ballroom A1.

PH in ILD: The Clouds Are Clearing, Monday October 17, 6:30 PM CT, featuring Jean Elwing, M.D., FCCP, University of Cincinnati; Lisa Lancaster, M.D., FCCP, Vanderbilt University; and Sandeep Sahay, M.D., FCCP, Houston Methodist Hospital. The symposium will be held at the Omni Nashville Hotel, Legends Ballroom E-G.

About TYVASO^® (treprostinil) Inhalation Solution and TYVASO DPI^® (treprostinil) Inhalation Powder

INDICATION

TYVASO (treprostinil) Inhalation Solution and TYVASO DPI (treprostinil) Inhalation Powder are prostacyclin mimetics indicated for the treatment of:

• Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies with TYVASO establishing effectiveness predominately included 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 clinical experience with inhaled treprostinil has been on a background of an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor. The controlled clinical experience with TYVASO was limited to 12 weeks in duration.

• Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study with TYVASO establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

• TYVASO and TYVASO DPI are pulmonary and systemic vasodilators. In patients with low systemic arterial pressure, either product may produce symptomatic hypotension.
• Both products inhibit platelet aggregation and increase the risk of bleeding.
• Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both C_max and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness.
• Like other inhaled prostaglandins, TYVASO and TYVASO DPI may cause acute bronchospasm. Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm. Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with TYVASO and TYVASO DPI.

DRUG INTERACTIONS/SPECIFIC POPULATIONS

• The concomitant use of either product with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension.
• Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both C_max and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to 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.

• Across clinical studies used to establish the effectiveness of TYVASO in patients with PAH and PH‑ILD, 268 (47.8%) patients aged 65 years and over were enrolled. The treatment effects and safety profile observed in geriatric patients were similar to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy.

ADVERSE REACTIONS

• Pulmonary Arterial Hypertension (WHO Group 1)
  
  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 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 3-week, open-label, single-sequence, safety and tolerability study (BREEZE) conducted in 51 patients on stable doses of TYVASO who switched to a corresponding dose of TYVASO DPI, the most commonly reported adverse events seen with TYVASO DPI in ≥4% of PAH patients during the 3-week treatment phase included cough (35.3%), headache (15.7%), dyspnea (7.8%), and nausea (5.9%).

• Pulmonary Hypertension Associated with ILD (WHO Group 3)
  
  In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions with TYVASO were similar to the experience in studies of PAH.

Please see Full Prescribing Information for TYVASO or TYVASO DPI, Instructions for Use manuals for TD-100 and TD-300 TYVASO^® Inhalation System and TYVASO DPI^™ Inhalation Powder, and additional information at www.TYVASOHCP.com or call 1‑877‑UNITHER (1-877-864-8437).

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About Orenitram^® (treprostinil) Extended-Release Tablets

Indication

Orenitram is a prostacyclin mimetic indicated for treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to delay disease progression and to improve exercise capacity. The studies that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (66%) or PAH associated with connective tissue disease (26%).

Important Safety Information for Orenitram

Contraindications

• Avoid use of Orenitram in patients with severe hepatic impairment (Child Pugh Class C) due to increases in systemic exposure.

Warnings and Precautions

• Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms.
• The Orenitram tablet shell does not dissolve. In patients with diverticulosis, Orenitram tablets can lodge in a diverticulum.

Adverse Reactions

• In the 12-week, placebo-controlled, monotherapy study, and an event-driven, placebo-controlled, combination therapy study, adverse reactions that occurred at rates at least 5% higher on Orenitram than on placebo included headache, diarrhea, nausea, vomiting, flushing, pain in jaw, pain in extremity, hypokalemia, abdominal discomfort, and upper abdominal pain.

Drug Interactions

• Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil increases exposure to treprostinil; therefore, Orenitram dosage reduction may be necessary in these patients.

Specific Populations

• Animal reproductive studies with Orenitram have shown an adverse effect on the fetus. There are no adequate and well-controlled studies with Orenitram in pregnant women.
• It is not known whether treprostinil is excreted in human milk or if it affects the breastfed infant or milk production.
• Safety and effectiveness of Orenitram in pediatric patients have not been established.
• Use of Orenitram in patients aged 65 years and over demonstrated slightly higher absolute and relative adverse event rates compared to younger patients. Caution should be used when selecting a dose for geriatric patients.
• There is a marked increase in the systemic exposure to treprostinil in hepatically impaired patients.

Please see Full Prescribing Information and Patient Information at www.orenitram.com or call 1-877-UNITHER (1-877-864-8437).

United Therapeutics: Enabling Inspiration

At United Therapeutics, our vision and mission are one. We use our enthusiasm, creativity, and persistence to innovate for the unmet medical needs of our patients and to benefit our other stakeholders. We are bold and unconventional. We have fun, we do good. 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.

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 upcoming medical conference posters and presentations, our opportunity to provide an update on both long-term data from the INCREASE and FREEDOM-EV open-label extension studies and real-world claims data analysis, 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 October 14, 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, TYVASO DPI, and ORENITRAM are registered trademarks of United Therapeutics Corporation.

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