Mini-symposia to focus on long-term extension data for the Tyvaso® INCREASE study, the ralinepag phase 2 study, and the Orenitram® FREEDOM-EV study
Poster presentations touch on real-world treprostinil use, Tyvaso DPI™, and other treprostinil clinical studies
United Therapeutics is hosting a sponsored symposium on PH-ILD and sponsoring the ATS 2022 Women’s Forum
SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.–(BUSINESS WIRE)–United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced that eight posters and three mini-symposia across the company’s commercial and development portfolio will be presented at the 2022 American Thoracic Society (ATS) International Conference, taking place May 13-18, 2022, in San Francisco. In addition, the company is hosting a sponsored symposium on pulmonary hypertension associated with interstitial lung disease (PH-ILD) and is sponsoring the ATS 2022 Women’s Forum.
“ATS 2022 will provide us with the opportunity to update the pulmonary hypertension community on long-term data with presentations on the INCREASE, FREEDOM-EV, and phase 2 ralinepag open label extension studies,” said Gil Golden, M.D., Ph.D., Chief Medical Officer of United Therapeutics. “This year’s conference will also allow us to feature poster presentations on Tyvaso DPI, the EXPEDITE study, the ADAPT registry, and real-world outcomes data for our treprostinil products.”
Mini-symposia include:
Mini-symposium, Sunday, May 15, 2:45 – 2:55 PM PT: A96 – Long-Term Data from Study APD811-007, an Open-Label Extension Study Evaluating Ralinepag for the Treatment of Pulmonary Arterial Hypertension. Presented by Elizabeth S. Klings, M.D., Boston University School of Medicine.
Mini-symposium, Sunday, May 15, 3:15 – 3:25 PM PT: A96 – Long-Term Efficacy of Oral Treprostinil in Subjects with Pulmonary Arterial Hypertension: FREEDOM-EV Open-Label Extension Study. Presented by R. James White, M.D., Ph.D., University of Rochester.
Mini-symposium, Monday, May 16, 3:35 – 3:45 PM PT: B96 – Long-Term Effects of Inhaled Treprostinil in Patients with Pulmonary Hypertension Due to Interstitial Lung Disease: The INCREASE Study Open-Label Extension. Presented by Aaron B. Waxman, M.D., Ph.D., Brigham and Women’s Hospital, Boston.
Posters include:
Thematic poster session, Monday, May 16, 11:15 AM – 1:15 PM PT: B53/P202 – Comparison of Pharmacokinetics of 3 Doses of Treprostinil Inhalation Powder (Tyvaso DPI) and 3 Doses of Tyvaso in Healthy Normal Volunteers. Presented by Kareem El-Kersh, M.D., University of Nebraska Medical Center.
Thematic poster session, Monday, May 16, 11:15 AM – 1:15 PM PT: B53/P203 – Rapid Titration of Parenteral Treprostinil to EXPEDITE Dosing of Oral Treprostinil. Presented by Vijay P. Balasubramanian, M.D., MRCP, University of California, San Francisco, Fresno.
Thematic poster session, Monday, May 16, 11:15 AM – 1:15 PM PT: B53/P205 – Strategies to EXPEDITE the Time to Effective Dosing of Oral Treprostinil in Patients with Pulmonary Arterial Hypertension. Presented by Chad E. Miller, M.D., Piedmont Healthcare Atlanta.
Thematic poster session, Monday, May 16, 11:15 AM – 1:15 PM PT: B52/P178 – Incidence and Predictors of Catheter-Related Adverse Events Among Medicare Adult Patients with Pulmonary Arterial Hypertension Using Intravenous Prostacyclin Therapy. Presented by Murali Chakinala, M.D., Washington University St. Louis.
Poster discussion session, Monday, May 16, 2:15 PM – 3:45 PM PT: B106/605 – Clinician-Based Risk Assessment Compared to REVEAL Lite 2 and Parenteral Prostacyclin Utilization in a Physician-Conducted Retrospective Chart Review of Patients with Pulmonary Arterial Hypertension. Presented by Amresh Raina, M.D., Allegheny General Hospital, Pittsburgh.
Poster discussion session, Monday, May 16, 2:15 – 3:45 PM PT: B106/607 – A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in Subjects with Pulmonary Arterial Hypertension (ADVANCE OUTCOMES). Presented by Vallerie Victoria Mclaughlin, M.D., University of Michigan Hospital.
Poster discussion session, Monday, May 16, 2:15 – 3:45 PM PT: B106/608 – Clinical Improvement in Pulmonary Arterial Hypertension (PAH) Patients Transitioning from Selexipag to Oral Treprostinil: Interim Results from the ADAPT Registry. Presented by Daniel J. Lachant, D.O., University of Rochester.
Rapid abstract poster discussion session, Tuesday, May 17, 2:15 PM – 3:45 PM PT: C105/504 – Comparative Effectiveness of Inhaled Treprostinil vs Iloprost in Patients with Pulmonary Arterial Hypertension: An Analysis of U.S. Administrative Claims Data. Presented by Charles D. Burger, M.D., Mayo Clinic Florida.
Sponsored events include:
Sponsored Symposium, Sunday, May 15, 6:30 PM – 9:30 PM PT, A New Frontier in PH-ILD: Screening, Diagnosis, and Treatment Options. Presented by Franck Rahaghi, M.D., MHS, FCCP, Cleveland Clinic Florida; Nicholas Kolaitis, M.D., MAS, University of California, San Francisco; and Steven Nathan, M.D., FCCP, Inova Fairfax Hospital.
The ATS 2022 Women’s Forum, Monday, May 16, 11:45 AM – 1:15 PM PT, featuring Patricia W. Finn, M.D., the Earl M. Bane professor, associate dean for strategic initiative, head of the Department of Medicine, and an associate program director for the Medical Scientist Training Program at the University of Illinois at Chicago.
About TYVASO® (treprostinil) Inhalation Solution
Eyebrow (abbreviated) Indication
- For the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability.
- For the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability.
INDICATION
TYVASO (treprostinil) is a prostacyclin mimetic indicated for the treatment of:
- Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies 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 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.
- Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study 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 is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, TYVASO may produce symptomatic hypotension.
- TYVASO inhibits platelet aggregation and increases the risk of bleeding.
- Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax 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.
DRUG INTERACTIONS/SPECIFIC POPULATIONS
- The concomitant use of TYVASO 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 Cmax 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 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.
- 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 were similar to the experience in studies of PAH.
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).
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).
About Remodulin® (treprostinil) Injection
Indication
Remodulin is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%).
In patients with PAH requiring transition from epoprostenol, Remodulin is indicated to diminish the rate of clinical deterioration. Consider the risks and benefits of each drug prior to transition.
Important Safety Information for Remodulin
Warnings and Precautions
- Chronic intravenous (IV) infusions of Remodulin delivered using an external infusion pump with an indwelling central venous catheter are associated with the risk of blood stream infections (BSIs) and sepsis, which may be fatal. Therefore, continuous subcutaneous (SC) infusion is the preferred mode of administration.
- Avoid abrupt withdrawal or sudden large reductions in dosage of Remodulin, which may result in worsening of PAH symptoms.
- Titrate slowly in patients with hepatic or renal insufficiency, because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic or renal function.
- Remodulin is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with Remodulin may produce symptomatic hypotension.
- Remodulin inhibits platelet aggregation and increases the risk of bleeding.
Adverse Reactions
- In clinical studies of SC Remodulin infusion, the most common adverse events reported were infusion site pain and infusion site reaction (redness, swelling, and rash). These symptoms were sometimes severe and sometimes required treatment with narcotics or discontinuation of Remodulin. The IV infusion of Remodulin with an external infusion pump has been associated with a risk of blood stream infections, arm swelling, paresthesias, hematoma, and pain. Other common adverse events (≥3% more than placebo) seen with either SC or IV Remodulin were headache (27% vs. 23%), diarrhea (25% vs. 16%), nausea (22% vs. 18%), rash (14% vs. 11%), jaw pain (13% vs. 5%), vasodilatation (11% vs. 5%), edema (9% vs. 3%), and hypotension (4% vs. 2%).
Drug Interactions
- Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn.
Specific Populations
- In patients with mild or moderate hepatic insufficiency, decrease the initial dose of Remodulin to 0.625 ng/kg/min of ideal body weight, and monitor closely. Remodulin has not been studied in patients with severe hepatic insufficiency.
- Safety and effectiveness of Remodulin 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.
- There are no adequate and well-controlled studies with Remodulin in pregnant women. It is not known whether treprostinil is excreted in human milk or if it affects the breastfed infant or milk production.
Please see accompanying Full Prescribing Information for Remodulin.
For additional information, visit www.RemodulinPro.com or call Customer Service at 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 upcoming medical conference posters and presentations, 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 29, 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, REMODULIN, and ORENITRAM are registered trademarks of United Therapeutics Corporation.
TYVASO DPI is a trademark of United Therapeutics Corporation.
Contacts
Dewey Steadman
(202) 919-4097
ir@unither.com