Significant Improvement in Six-Minute Walk Distance of 59.4 Meters and in Time
to Clinical Worsening with No Observed Liver Function Abnormalities
DENVER, Dec. 12 /PRNewswire-FirstCall/ -- Myogen, Inc. (Nasdaq: MYOG)
today announced positive top line results of the ARIES-2 trial, the first
pivotal Phase 3 trial evaluating ambrisentan, an oral endothelin receptor
antagonist (ERA), in pulmonary arterial hypertension (PAH). The trial met the
primary efficacy endpoint of improved exercise capacity, the key secondary
endpoint of time to clinical worsening and several other secondary efficacy
endpoints.
The primary efficacy endpoint of the ARIES-2 trial was the
placebo-corrected mean change in six-minute walk distance (6MWD) at week 12
compared to baseline. Results of the trial demonstrated that with once-daily
dosing, 5 mg of ambrisentan improved the placebo-corrected mean 6MWD by 59.4
meters (p=0.0002) and 2.5 mg of ambrisentan improved the placebo-corrected
mean 6MWD by 32.3 meters (p=0.0219). For the placebo group, the mean 6MWD at
week 12 decreased from baseline by 10.1 meters. Improvements in time to
clinical worsening compared to placebo were observed for both the 5 mg dose
group (p=0.0076) and the 2.5 mg dose group (p=0.0048).
The trial safety results demonstrated ambrisentan was generally well
tolerated. The most frequent adverse event was headache, which occurred in
12.7% of patients in the 5 mg dose group and 7.8% in the 2.5 mg dose group,
compared to 6.2% in the placebo group. No patients treated with ambrisentan
developed serum aminotransferase concentrations greater than three-times the
upper limit of the normal range, compared to one patient in the placebo group.
Ambrisentan had no apparent effect on the activity or dosage of warfarin-type
anticoagulants commonly prescribed for patients with PAH.
"We believe the robustness of these results is unprecedented for oral
therapies for patients with pulmonary arterial hypertension and represents a
significant achievement for ambrisentan and Myogen," said J. William Freytag,
President and Chief Executive Officer of Myogen. "We greatly appreciate the
support and efforts of the ARIES-2 clinical sites. Based on the properties of
ambrisentan and the clinical results obtained to date, we believe that, if
approved, ambrisentan has the potential to offer significant advantages over
other endothelin receptor antagonists for the treatment of PAH. We are
excited by the progress of the ambrisentan clinical program and look forward
to learning the results of ARIES-1 in the second quarter of 2006."
"The top line results of this trial fulfilled our expectations in every
regard," said Dr. Michael Gerber, Senior Vice President of Clinical
Development and Regulatory Affairs for Myogen. "The magnitude of improvement
in six-minute walk distance and dose-response for the primary endpoint were
impressive. Furthermore, the delay in clinical worsening observed at week 12
for both dose groups compared to placebo was remarkable. These results and
those of our long-term Phase 2 trial suggest that, if approved, ambrisentan
could ultimately represent a major treatment advance for patients with
pulmonary arterial hypertension."
In January 2004, Myogen announced the initiation of two pivotal Phase 3
clinical trials, ARIES-1 and ARIES-2, evaluating the safety and efficacy of
ambrisentan in patients with PAH. The ARIES trials are randomized,
double-blind, placebo-controlled trials of identical design except for the
doses of ambrisentan studied and the geographic locations of the investigative
sites. Both trials were designed to enroll 186 patients (62 patients per dose
group). ARIES-1 will evaluate once-daily doses of 5 mg and 10 mg of
ambrisentan. ARIES-2 evaluated once-daily doses of 2.5 mg and 5 mg of
ambrisentan. The primary efficacy endpoint is exercise capacity, measured as
the mean change from baseline at 12 weeks in the 6MWD compared to placebo.
Secondary endpoints include time to clinical worsening, World Health
Organization (WHO) functional class, SF-36(TM) Health Survey, and Borg dyspnea
index. ARIES-2 enrolled 192 patients primarily from Europe, while ARIES-1
enrolled 202 patients primarily from the United States. The Company expects
to report top line results for ARIES-1 in the second quarter of 2006.
In addition, more than 300 patients continue ambrisentan treatment in
long-term trials with maximum exposure of more than three years.
The top line results of the ARIES-2 trial and the results to date of
Myogen's Phase 2 trial of ambrisentan in PAH and related long-term study 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 in patients with WHO functional
class II symptoms relative to those with 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
- 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.
Conference Call
J. William Freytag, President and CEO, and other members of Myogen's
senior management will discuss the ARIES-2 top line results via webcast and
conference call on Monday, December 12, 2005 at 8:30 am Eastern. To access
the live webcast, please log on to the Company's website at
http://www.myogen.com and go to the Investor Relations section.
Alternatively, callers may participate in the conference call by dialing
800-366-3908 (domestic) or 011-1-303-262-2140 (international). Webcast and
telephone replays of the conference call will be available approximately two
hours after the completion of the call through Friday, December 30, 2005.
Callers can access the replay by dialing 800-405-2236 (domestic) or
011-1-303-590-3000 (international). The passcode is 11048390#.
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 ARIES-2 clinical trial, summary
statements relating to the 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 ARIES-2 trial, are
not necessarily predictive of future clinical results, including possible
results of the ARIES-1 trial. 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, 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 December
12, 2005. 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., +1-303-464-3986, derek.cole@myogen.com
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