Patients with PAH Who Previously Discontinued Other ERA Therapy Due to Liver
Function Abnormalities Treated with Long-term Ambrisentan Therapy
DENVER, Feb. 13 /PRNewswire-FirstCall/ -- Myogen, Inc. (Nasdaq: MYOG)
today announced positive top line results of the AMB-222 study, an open-label
study of ambrisentan in patients with pulmonary arterial hypertension (PAH)
who have previously discontinued bosentan and/or sitaxsentan treatment due to
liver function abnormalities. None of the 36 patients enrolled in the study
had a recurrence of liver function abnormalities that resulted in
discontinuation of ambrisentan during the initial 12-week evaluation period
(the primary endpoint of the study). One patient had a transient serum
aminotransferase test result greater than three-times the upper limit of the
normal range (3xULN) at week 12 that resulted in dose reduction from 5 mg to
2.5 mg ambrisentan. This patient remains on ambrisentan therapy and has not
had a recurrence of serum aminotransferases greater than 3xULN. Patients have
continued to receive ambrisentan therapy for periods up to 9 months (mean
exposure of 6 months) and no further occurrence of serum aminotransferase
concentrations greater than 3xULN has been observed.
"These results suggest that for patients who have had to stop treatment
with other endothelin receptor antagonists due to liver function
abnormalities, ambrisentan may offer an opportunity to resume treatment,"
stated Michael J. Gerber, MD, Senior Vice President of Clinical Development
and Regulatory Affairs for Myogen. "I believe ambrisentan has the potential
to be an important therapeutic option for these patients with PAH and their
physicians. The low incidence and severity of liver function test
abnormalities demonstrated in the ARIES-2 trial and the AMB-222 rescue study
are very encouraging. Ambrisentan has a chemical structure that differs from
those of bosentan and sitaxsentan. We believe that this distinction may
underlie ambrisentan's low propensity to cause liver function abnormalities."
Myogen announced the initiation of AMB-222 in May 2005 with a target
enrollment of 30 patients. A total of 36 patients were enrolled in the study,
of which 31 (86%) had discontinued bosentan, 2 (6%) had discontinued
sitaxsentan and 3 (8%) had discontinued both bosentan and sitaxsentan,
sequentially, due to serum aminotransferase abnormalities. Also, 17 (47%) of
the patients were receiving concomitant sildenafil therapy. Patients received
2.5 mg of ambrisentan once daily for 4 weeks and then the dose was increased
to 5 mg of ambrisentan once daily. The last patient reached the 12-week
endpoint evaluation in January 2006. All patients had the option to continue
ambrisentan therapy after the initial 12-week assessment period.
The primary endpoint of the trial was the incidence of serum
aminotransferase concentrations greater than 3xULN during the 12-week
evaluation period that were related to ambrisentan and resulted in
discontinuation of drug.
The top line results of the ARIES-2 and AMB-222 trials, as well as the
results to date of Myogen's Phase 2 trial of ambrisentan in PAH (AMB-220) and
related long-term study (AMB-220-E) have demonstrated:
* Improvement in exercise capacity that is significant, early in onset and
durable
* Significant improvement in time to clinical worsening
* Comparable benefit in exercise capacity for patients with WHO functional
class II and class III symptoms
* An apparent survival benefit when compared with predicted survival based
on the National Institutes of Health Registry formula
* Effectiveness with once-daily dosing and the potential for dose
flexibility
* Low incidence and severity of liver function test abnormalities at all
doses
* Potential utility in resuming endothelin receptor antagonist (ERA)
treatment in patients who have discontinued bosentan or sitaxsentan
treatment due to liver function abnormalities
* No apparent drug-drug interactions with warfarin-type anticoagulants
Based on results to date and the properties of ambrisentan, Myogen
believes that, if ambrisentan is ultimately approved, it may offer significant
clinical benefit to PAH patients not provided by other PAH therapies.
About Pulmonary Arterial Hypertension
PAH is a highly debilitating disease characterized by severe constriction
of the blood vessels in the lungs leading to very high pulmonary arterial
pressures. These high pressures make it difficult for the heart to pump blood
through the lungs to be oxygenated. Patients with PAH suffer from extreme
shortness of breath as the heart struggles to pump against these high
pressures causing such patients to ultimately die of heart failure. PAH can
occur with no known underlying cause, or it can occur secondary to diseases
such as connective tissue disease, congenital heart defects, cirrhosis of the
liver and HIV infection. PAH afflicts approximately 200,000 patients
worldwide.
About Ambrisentan
Ambrisentan is an investigational drug being developed as a once daily
oral therapy for patients with PAH and has been granted orphan drug
designation for the treatment of PAH in both the United States and European
Union.
Ambrisentan is a non-sulfonamide, propanoic acid-class, type-A selective
endothelin receptor antagonist. Endothelin is a small peptide hormone that
plays a critical role in the control of blood flow and cell growth. Elevated
endothelin blood levels are associated with several cardiovascular disease
conditions, including pulmonary arterial hypertension, chronic renal disease,
coronary artery disease, hypertension and chronic heart failure. The Company
believes that agents that block the detrimental effects of endothelin may
provide significant benefits in the treatment of these conditions.
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 has two product
candidates in late-stage clinical development: ambrisentan for the treatment
of patients with pulmonary arterial hypertension and darusentan for the
treatment of patients with resistant hypertension. The Company 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 summary statements relating to
the top line results of the Company's AMB-222 clinical trial, summary
statements relating to the top line results of the ARIES-2 trial and results
of the Company's Phase 2 trial of ambrisentan in patients with PAH and the
related extension trial, and summary statements relating to the potential
efficacy and safety profile of ambrisentan. Actual results could differ
materially from those projected and the Company cautions investors not to
place undue reliance on the forward-looking statements contained in this
release.
Results from clinical trials, including the Company's AMB-222 trial, are
not necessarily predictive of future clinical results, including results of
the ARIES-1 trial of ambrisentan in patients with PAH. Top line results may
not be confirmed upon full analysis of the detailed results of a trial and
additional information relating to the safety, efficacy or tolerability of the
Company's product candidates, including ambrisentan, may be discovered upon
further analysis of trial data and upon review and analysis of additional
trial data, including data from the Company's ongoing ARIES-1 trial and its
Phase 2 and Phase 3 extension trials of ambrisentan in patients with PAH. If
the Company's product candidates do not meet 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 the Company's product
candidates meet safety and efficacy endpoints, regulatory authorities may not
approve them, the Company may not be able to successfully market them, or the
Company may face post-approval problems that require the withdrawal of its
product from the market. There can be no assurance that Myogen's product
candidates, including ambrisentan, will be proven safe and effective for use
in humans. Abnormal elevations of liver function test results, including
elevated serum aminotransferase concentrations, have been reported in trials
of other endothelin receptor antagonists. The Company's results may be
affected by its effectiveness at managing its financial resources, its ability
to successfully develop and market its product candidates, its ability to
obtain and enforce patent protection for its products, competition from other
biotechnology and pharmaceutical companies, difficulties or delays in
manufacturing its products, and regulatory developments involving current and
future products. Delays in initiating or conducting clinical trials, whether
caused by competition, adverse events, patient enrollment rates, regulatory
issues or other factors, could adversely affect the Company's financial
position and prospects. 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 reports on Form 10-Q and Form 8-
K. It is Myogen's policy to only update or reconfirm its public guidance by
issuing a press release or filing a periodic or current report with the
Securities and Exchange Commission. The Company generally plans to provide
guidance as part of its annual and quarterly earnings releases but reserves
the right to provide guidance at different intervals or to revise its practice
in future periods. All information in this press release is as of February
13, 2006. Myogen undertakes no duty or obligation to update any forward-
looking statements contained in this release as a result of new information,
future events or changes in the Company's expectations. The Company also
disclaims any duty to comment upon or correct information that may be
contained in reports published by the investment community.
SOURCE Myogen, Inc.
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Related links:
http://www.myogen.com
CONTACT:
Derek K. Cole, Director, Investor Relations
of Myogen, Inc., 303-464-3986, or derek.cole@myogen.com
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