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Treprostinil Data Presented at American Thoracic Society Conference Demonstrates Significant Clinical Progress in All Four Routes of Administration; First Presentation of Full Data Set from the TRIUMPH-1 Trial of Inhaled Treprostinil


5/22/2008 11:13:16 AM

SILVER SPRING, Md., May 21 /PRNewswire-FirstCall/ -- United Therapeutics Corporation and its wholly-owned subsidiary Lung Rx, Inc. today announced that data from seven presentations concerning the treatment of pulmonary arterial hypertension (PAH) with treprostinil were reported at the American Thoracic Society (ATS) meeting in Toronto, Ontario. The ATS presentations involved treprostinil delivered by inhaled, oral, intravenous and subcutaneous routes of administration.

"It has always been our goal to build a portfolio of products from the remarkable treprostinil molecule that will create viable treatment options for patients along the full continuum of this life-threatening disease," said Martine Rothblatt, Ph.D., United Therapeutics' Chairman and Chief Executive Officer. "The results of these diverse studies covering all four routes of delivery are bringing us just that much closer to realizing our goal."

Inhaled Treprostinil

In TRIUMPH-1: Discussion of Inhaled Treprostinil Sodium in Patients with PAH, Dr. Vallerie McLaughlin, Director of the Pulmonary Hypertension Program at the University of Michigan, presented the full data set from the TRIUMPH-1 study of investigational inhaled treprostinil. Dr. McLaughlin's presentation confirmed that six-minute walk (6MW) distance increased by approximately 20 meters in patients receiving inhaled treprostinil as compared to patients receiving placebo, with a durable and significant effect on 6MW distance observed at trough exposure.

Dr. McLaughlin also presented data showing that inhaled treprostinil improved both quality of life and levels of NT-pro-BNP, a plasma biomarker of cardiac function, in patients receiving inhaled treprostinil as compared to patients receiving placebo. Patients receiving inhaled treprostinil showed a median decrease in NT-pro-BNP levels of 57 pg/ml at 12 weeks, as compared to a median increase of 40 pg/ml at 12 weeks in those patients receiving placebo.

Dr. McLaughlin also highlighted the convenience of inhaled treprostinil, which is administered via four one-minute inhalation sessions per day.

The TRIUMPH-1 (TReprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension) trial was a randomized, double-blind, placebo-controlled trial of patients with severe PAH. The study population consisted of 235 patients who were optimized on an approved oral therapy for PAH, either bosentan (Tracleer(R)), an endothelin receptor antagonist, or sildenafil (Revatio(R)), a phosphodiesterase-5 inhibitor. In addition to one of these oral therapies, patients were administered inhaled treprostinil or placebo in four daily inhalation sessions with a maximum dose of 54 micrograms per session over the course of the 12-week trial.

Oral Treprostinil

In Plasma Levels with Oral Treprostinil Dietholamine over a Wide Range of Doses in Patients with PAH, Dr. R. James White of the University of Rochester presented data from a 12-patient study showing that a sustained-release capsule of treprostinil administered twice daily allowed patients to maintain consistent therapeutic levels of treprostinil in their bloodstreams in an equivalent therapeutic range to intravenously or subcutaneously administered treprostinil. The pharmacokinetic profile demonstrated that the release of treprostinil from the oral dosage form was sustained and supported the twice-daily regimen used in United Therapeutics' ongoing Phase 3 FREEDOM studies of oral treprostinil in patients with PAH. Dr. White's presentation also highlighted that the dose of oral treprostinil administered to each patient showed a linear correlation with total plasma exposure (AUC) and maximum exposure (Cmax). This is an important finding that supports the ability to reliably titrate oral treprostinil to therapeutic levels.

Intravenous Treprostinil

In Intravenous Treprostinil Effect on Angiopoietin-2 Levels During 12 Weeks of Blinded Therapy: a Study of 11 Biomarkers in PAH, Dr. R. James White presented results of his biomarker study demonstrating that intravenously administered treprostinil sodium (Remodulin(R)) decreased the presence of a specific protein that contributes to PAH -- Angiopoietin-2 -- in 12 of 13 patients. This study was part of the first randomized, placebo-controlled trial of an infused prostacyclin in patients with PAH. The primary endpoint of this randomized, placebo-controlled study, change in 6MW distance, showed an 83-meter improvement as compared to placebo.

In Treatment Effects Following Rapid Switch to IV Treprostinil in Stable PAH Patients, Dr. Omar A. Minai of the Cleveland Clinic presented data from an ongoing single-center, 8-week study of treatment satisfaction of PAH patients who switched from epoprostenol (Flolan(R)) to intravenous Remodulin. Rapid switch from Flolan to Remodulin occurred by directly switching the infusion pump reservoir. Dr. Minai reported that no patients experienced clinical deterioration or change in functional class, and he also observed a favorable impact on quality of life as early as 8 weeks following transition. He noted that time spent by patients on drug preparation decreased by 44 percent with Remodulin as compared to Flolan.

In Multi-Center Experience with Transition to Treprostinil from Inhaled Iloprost in PAH, Dr. Robert Frantz of the Mayo Clinic presented a retrospective chart review that evaluated best practices principally surrounding transitions from inhaled iloprost (Ventavis(R)) to intravenous Remodulin. Medical records were assessed to determine the reason for transition, transition procedure, dose titrations and clinical outcomes. The primary reason for transition in all patients was worsening PAH, with non-compliance with the Ventavis dosing regimen reported as a secondary reason for transition. Most patients transitioned to Remodulin in an inpatient setting, but many patients were successfully transitioned at home with the assistance of an infusion nurse. The authors reported that 6MW distances were maintained post-transition, no serious adverse events occurred due to the switch, and adverse events were consistent with known prostacyclin side effects.

In Long-Term IV Treprostinil in Pediatric PAH, Dr. Cherise Rowan of the Columbia University Medical Center presented data from an independent retrospective chart review of 16 pediatric patients transitioned from Flolan to Remodulin between 2004 and 2007. Based on clinical observations and hemodynamic data, the authors of this analysis concluded that transition of children with stable PAH from long-term intravenous Flolan to intravenous Remodulin appears safe with efficacy maintained.

Subcutaneous Treprostinil

In Subcutaneous Treprostinil for Severe PAH: Hemodynamic and Clinical Outcomes Discussion, Dr. Francisco J. Soto of the Medical College of Wisconsin presented independent data from a cohort of 52 PAH patients receiving subcutaneous Remodulin over a period of 5 years. He noted that substantial improvements were seen in hemodynamics, 6MW distance, BNP and NYHA functional class at an average duration of more than one year. Key success factors in the response with subcutaneous Remodulin included rapid dose escalation to a minimum target of 40 ng/kg/min, infrequent subcutaneous catheter site changes, and proactive pain management. The authors conclude that once patients overcome the initial obstacles of subcutaneous administration of Remodulin (e.g., infusion site pain), they tolerate treatment very well and sustain durable clinical and hemodynamic benefits.

Investor Q&A Session

United Therapeutics will host an investor Q&A session following the conclusion of the ATS conference at The Westin Harbour Castle, One Harbour Square, Toronto, Ontario, on May 21, 2008, at 5:00 pm EDT. Vallerie McLaughlin, MD, Director of the Pulmonary Hypertension Program at the University of Michigan, will join United Therapeutics' senior management in this Q&A session, which is also being webcast and can be accessed via United Therapeutics' website at http://ir.unither.com/events.cfm.

About Remodulin

Remodulin is indicated for the treatment of PAH in patients with NYHA Class II-IV symptoms to diminish symptoms associated with exercise. It may be administered as a continuous subcutaneous infusion or continuous intravenous infusion; however, because of the risks associated with chronic indwelling central venous catheters, including serious blood stream infections, continuous intravenous infusion should be reserved for patients who are intolerant of the subcutaneous route, or in whom these risks are considered warranted.

Remodulin is indicated to diminish the rate of clinical deterioration in patients requiring transition from Flolan(R); the risks and benefits of each drug should be carefully considered prior to transition.

Important Safety Information

Chronic intravenous infusions of Remodulin are delivered using an indwelling central venous catheter. This route is associated with the risk of blood stream infections (BSI) and sepsis, which may be fatal. Remodulin is contraindicated in patients with hypersensitivity to Remodulin, its ingredients, or similar drugs. Remodulin is a potent vasodilator. It lowers blood pressure, which may be further lowered by other drugs that also reduce blood pressure. Remodulin inhibits platelet aggregation and therefore, may increase the risk of bleeding, particularly in patients on anticoagulants. Abrupt withdrawal or sudden large reductions in dosage of Remodulin may result in worsening of PAH symptoms and should be avoided. Caution should be used in patients with hepatic or renal problems. The most common side effects of Remodulin included those related to the method of infusion. For subcutaneous infusion, infusion site pain and infusion site reaction (redness and swelling) occurred in the majority of patients. These symptoms were often severe and could lead to treatment with narcotics or discontinuation of Remodulin. For intravenous infusion, line infections, sepsis, arm swelling, paresthesias, hematoma and pain were most common. General side effects (>5% more than placebo) were diarrhea, jaw pain, vasodilation, and edema.

About United Therapeutics and Lung Rx

United Therapeutics Corporation is a biotechnology company focused on the development and commercialization of unique products to address the unmet medical needs of patients with chronic and life-threatening cardiovascular and infectious diseases and cancer.

Lung Rx, Inc. is a biotechnology company focused on unmet medical needs in pulmonary medicine and pulmonary delivery of innovative therapeutic products. [uthr-g]

CONTACT: Andrew Fisher of United Therapeutics Corporation,
+1-202-483-7000, Afisher@unither.com

Web site: http://www.unither.com/


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