DENVER, May 19 /PRNewswire-FirstCall/ -- Myogen, Inc. (Nasdaq: MYOG), a
biopharmaceutical company focused on the discovery, development and
commercialization of small molecule therapeutics for the treatment of
cardiovascular disorders, today announced the initiation of a clinical trial
to evaluate ambrisentan in patients with pulmonary arterial hypertension (PAH)
who have previously discontinued bosentan or sitaxsentan therapy due to liver
function test (LFT) abnormalities, specifically elevated serum
aminotransferase concentrations.
The primary objective of this trial is to determine the incidence of
increased serum aminotransferase concentrations associated with ambrisentan
therapy in patients who have previously discontinued bosentan or sitaxsentan
therapy due to serum aminotransferase abnormalities. This trial will also
evaluate the overall safety, tolerability and efficacy of ambrisentan in this
patient population. Approximately 30 patients will receive 2.5 mg ambrisentan
daily for 4 weeks followed by 5 mg of ambrisentan daily. Patients will be
monitored with clinical laboratory tests every 2 weeks and assessed for safety
and efficacy every 4 weeks during the first 12 weeks of treatment. The
primary endpoint will be assessed after the first 12 weeks of treatment.
Patients who complete week-48 in the extended portion of the study have the
option to receive 10 mg of ambrisentan daily.
Previous clinical trials with bosentan (BREATHE-1) and sitaxsentan
(STRIDE-1) have demonstrated dose-dependent increases in serum
aminotransferase concentrations, specifically alanine aminotransferase (ALT)
and/or aspartate aminotransferase (AST) concentrations, requiring withdrawal
of therapy for reasons of safety. Preclinical studies suggest that serum
aminotransferase elevations induced by bosentan and chemically-related
compounds may be due to their direct competition with bile salts for active
transport across the hepatocyte membrane into the bile canaliculi. We believe
an endothelin receptor antagonist (ERA) such as ambrisentan that has a
distinctly different chemical composition and metabolic pathway may result in
less competition with endogenous bile salts for canalicular transport. In
addition, ambrisentan demonstrated significant efficacy when administered at
daily doses of 1 to 10 mg, doses that are 10-250 times lower than the approved
daily dose of bosentan (125 mg bid) and the proposed daily dose of sitaxsentan
(100 mg once daily). We believe these lower doses might introduce less
competition on a molar basis for canalicular transport, which could result in
a lower incidence and severity of serum aminotransferase elevations.
About Ambrisentan
Ambrisentan is an ETA selective endothelin receptor antagonist being
developed as an oral therapy for patients with PAH. Ambrisentan has been
granted orphan drug designation for the treatment of PAH in both the United
States and European Union. The Company completed a Phase 2 clinical trial of
ambrisentan in September 2003.
In January 2004, Myogen initiated two pivotal Phase 3 clinical trials,
ARIES-1 & ARIES-2, for ambrisentan in PAH. The ARIES trials are randomized,
double-blind, placebo-controlled trials of identical design except for the
doses of ambrisentan and the geographic locations of the investigative sites.
The study design anticipates enrolling 186 patients (62 patients per dose
group) in each trial. ARIES-1 will evaluate ambrisentan doses of 5.0
milligrams and 10.0 milligrams administered orally once per day for 12 weeks.
ARIES-2 will evaluate ambrisentan doses of 2.5 milligrams and 5.0 milligrams
administered orally once per day for 12 weeks. The primary efficacy endpoint
is exercise capacity, measured as the change from baseline in the six-minute
walk test distance compared to placebo. Secondary endpoints include Borg
Dyspnea Index, World Health Organization (WHO) Functional Class and time to
clinical worsening. ARIES-1 is being conducted both in the United States and
abroad, while ARIES 2 is being conducted outside of the United States. The
Company expects to complete enrollment in ARIES-2 by the end of June 2005 and
ARIES-1 in the fourth quarter of 2005. The Company plans to report
preliminary results from each study approximately six months following the
completion of enrollment in that trial.
About Myogen
Myogen is a biopharmaceutical company focused on the discovery,
development and commercialization of small molecule therapeutics for the
treatment of cardiovascular disorders. Myogen currently markets one product
in Europe for the treatment of acute decompensated heart failure and has three
product candidates in late-stage clinical development: enoximone capsules for
the treatment of patients with chronic heart failure, ambrisentan for the
treatment of patients with pulmonary arterial hypertension and darusentan for
the treatment of patients with resistant hypertension. The Company, in
collaboration with Novartis, also conducts a target and drug discovery
research program focused on the development of disease-modifying drugs for the
treatment of chronic heart failure and related cardiovascular disorders.
Please visit Myogen's website at http://www.myogen.com.
Safe Harbor Statement
This press release contains forward-looking statements that involve
significant risks and uncertainties, including the statements relating to the
potential of ambrisentan as a treatment for PAH and its effect in patients who
have experienced elevated LFTs while taking other therapies. Actual results
could differ materially from those projected and Myogen cautions investors not
to place undue reliance on the forward-looking statements contained in this
release.
The results of Myogen's prior clinical trials of its product candidates,
including ambrisentan, do not necessarily predict the results of later-stage
clinical trials. Preliminary results may not be confirmed upon full analysis
of the detailed results of a trial. There can be no assurance that Myogen's
product candidates, including ambrisentan, have better safety profiles than
competing products, including a lower incidence of liver toxicity or liver
toxicity that is not dose dependent. Among other things, Myogen's results may
be affected by competition from other pharmaceutical and biotechnology
companies, Myogen's ability to successfully develop and market its current
products, difficulties or delays in its clinical trials, regulatory
developments involving current and future products and its effectiveness at
managing its financial resources. If the Company's product candidates,
including ambrisentan, darusentan, and enoximone, do not meet the safety or
efficacy endpoints in clinical evaluations, they will not receive regulatory
approval and the Company will not be able to market them. Even if Myogen's
product candidates meet safety and efficacy endpoints, regulatory authorities
may not approve them, or the Company may face post-approval problems that
require the withdrawal of its products from the market. If the Company is
unable to raise additional capital when required or on acceptable terms, it
may have to significantly delay, scale back or discontinue one or more of its
drug development or discovery research programs. Myogen is at an early stage
of development and may not ever have any products that generate significant
revenue.
Additional risks and uncertainties relating to the company and its
business can be found in the "Risk Factors" section of Myogen's Form 10-K for
the year ended December 31, 2004 and Myogen's periodic reports on Form 10-Q
and Form 8-K. Myogen is providing the information contained in this release
as of the date of the release and does not undertake any obligation to update
any forward-looking statements as a result of new information, future events
or otherwise.
SOURCE Myogen, Inc.
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Related links:
http://www.myogen.com
CONTACT:
Derek K. Cole, Director, Investor Relations
of Myogen, Inc., +1-303-464-3986, derek.cole@myogen.com
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