Myogen (NASDAQ:MYOG)
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Myogen, Inc. (Nasdaq: MYOG) today announced positive top
line results of the ARIES-1 trial, the second 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 for both ambrisentan
dose groups, with an excellent safety profile and no observed liver
function abnormalities in the ambrisentan treatment groups. On the
basis of the results of ARIES-1 & -2, Myogen expects to submit the
ambrisentan New Drug Application to the U.S. Food and Drug
Administration (FDA) in the fourth quarter of 2006.
The primary efficacy endpoint of the ARIES-1 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, 10 mg of ambrisentan improved the
placebo-corrected mean 6MWD by 51.4 meters (p=0.0001) and 5 mg of
ambrisentan improved the placebo-corrected mean 6MWD by 30.6 meters
(p=0.0084), indicating improved exercise capacity. For the placebo
group, the mean 6MWD at week 12 decreased from baseline by 7.8 meters.
Time to clinical worsening did not reach statistical significance
likely due to the relatively low incidence of clinical worsening
events observed in the trial. Other secondary endpoints had clinically
relevant improvements that achieved p values of less than 0.05 but
were not considered statistically significant due to the pre-specified
approach for multiple comparisons.
The trial safety results demonstrated ambrisentan was generally
well tolerated. The most frequent adverse event was peripheral edema.
No patients treated with ambrisentan developed serum aminotransferase
concentrations greater than three times the upper limit of the normal
range at any time during the 12 week treatment period, compared to two
patients in the placebo group, only one of which was confirmed upon
re-test. Ambrisentan had no apparent effect on the activity or dosing
of warfarin-type anticoagulants commonly co-administered to patients
with PAH.
The delivery of the ARIES-1 trial results triggers a $5.25 million
milestone payment under Myogen's ambrisentan sublicense agreement with
GlaxoSmithKline.
"With two positive, well-controlled studies demonstrating robust
efficacy and a safety database of more than 400 patients on long-term
treatment, we have the foundation for high quality regulatory
submissions worldwide," said Dr. Michael Gerber, Senior Vice President
of Clinical Development and Regulatory Affairs for Myogen. "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."
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
were 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 evaluated
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 was 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-1 enrolled 202 patients primarily from the United
States while ARIES-2 enrolled 192 patients primarily from Europe. In
addition, approximately 400 patients continue ambrisentan treatment in
long-term trials with maximum exposure of more than three years.
To date, the results of clinical studies have indicated that
ambrisentan may provide some or all of the following benefits to PAH
patients:
-- Improvement in exercise capacity that is significant, early in
onset and durable
-- Significant improvement in time to clinical worsening
-- Low incidence and severity of liver function test
abnormalities at all doses treated
-- Comparable benefit in exercise capacity in 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
-- Potential utility in resuming endothelin receptor antagonist
(ERA) treatment in patients who have discontinued treatment
with the alternative ERAs, bosentan or sitaxsentan, or both,
due to liver function abnormalities
-- No clinically relevant drug-drug interactions with
warfarin-type anticoagulants or sildenafil, a PDE-5 inhibitor
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. GlaxoSmithKline sublicensed commercial rights for
ambrisentan outside of the United States.
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-1 top line results
via webcast and conference call on Monday, April 10, 2006 at 8:30 am
Eastern. To access the live webcast, please log on to the Company's
website at www.myogen.com and go to the Investor Relations section.
Alternatively, callers may participate in the conference call by
dialing 800-219-6110 (domestic) or 011-1-303-262-2194 (international).
Webcast and telephone replays of the conference call will be available
approximately two hours after the completion of the call through
Friday, April 28, 2006. Callers can access the replay by dialing
800-405-2236 (domestic) or 011-1-303-590-3000 (international). The
passcode is 11058293#.
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.
Myogen and GlaxoSmithKline have entered into a global PAH partnership
in which Myogen has distribution and marketing rights to
GlaxoSmithKline's Flolan (epoprostenol sodium) in the United States
for the treatment of PAH and GlaxoSmithKline has sublicensed
ambrisentan from Myogen for all territories outside of the United
States. Myogen 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 www.myogen.com.
About Flolan (epoprostenol sodium)
Flolan was approved by the FDA in 1995 and is indicated for the
long-term intravenous treatment of primary pulmonary hypertension and
pulmonary hypertension associated with the scleroderma spectrum of
disease in NYHA Class III and Class IV patients who do not respond
adequately to conventional therapy. Use of Flolan is contraindicated
in patients with congestive heart failure due to severe left
ventricular systolic dysfunction. Flolan should not be used in
patients who develop pulmonary edema during dose initiation. Flolan is
also contraindicated in patients with known hypersensitivity to the
drug or structurally related compounds. Flolan should be used only by
clinicians experienced in the diagnosis and treatment of pulmonary
hypertension. The diagnosis of PPH or PH/SSD should be carefully
established. Please consult complete prescribing information for
Flolan at www.gsk.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-1
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.
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 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 a Phase 2 trial of ambrisentan
and 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 regulatory approvals or in initiating or conducting clinical
trials, whether caused by regulatory issues, competition, adverse
events, patient enrollment rates 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 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, 2005 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 April 10, 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.