First Presentation of Full Data Set from the TRIUMPH-1 Trial of Inhaled Treprostinil SILVER SPRING, Md., May 21
SILVER SPRING, Md., May 21 /PRNewswire-FirstCall/ -- United Therapeutics
Corporation (Nasdaq: UTHR) 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.
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SOURCE United Therapeutics Corporation
