Myogen (NASDAQ:MYOG)
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Myogen, Inc. (Nasdaq: MYOG) today announced results for
the integrated analysis of ARIES-1 and ARIES-2, the pivotal Phase 3
trials evaluating ambrisentan, an oral endothelin receptor antagonist
(ERA), in pulmonary arterial hypertension (PAH). The integrated
analysis was prospectively defined as a supportive analysis of the
ARIES trials' results and was detailed in a data analysis plan
submitted to the U.S. Food and Drug Administration prior to unblinding
the data for either ARIES trial.
The primary efficacy endpoint, placebo-corrected mean change in
six-minute walk distance at week 12 compared to baseline, demonstrated
a robust, dose-dependent increase in exercise capacity with
statistical significance for the combined data for all doses
(p less than 0.0001, linear regression model) and for each individual
ambrisentan dose.
-0-
*T
Dose Group Change in 6MWD Nominal p-value
----------------------------------------------------------------------
2.5 mg (n=64) 32.3 meters 0.0219
5 mg (n=130) 44.6 meters less than 0.0001
10 mg (n=67) 51.4 meters 0.0001
*T
Improvement in time to clinical worsening, a key secondary
endpoint and measure of disease progression, was significant for the
combined dose analysis (p = 0.0003) and for each of the three
individual ambrisentan dose groups (p less than 0.05 for each group).
All other prespecified secondary efficacy endpoints, including WHO
functional class, SF-36(R) Health Survey and Borg dyspnea index,
demonstrated statistically significant improvements for the combined
data for all dose groups and for the 5 mg and 10 mg doses (p less than
0.05 for each group).
Preliminary analysis of the top line safety results demonstrated
that ambrisentan was well tolerated. The most frequent adverse event
was peripheral edema, which was primarily mild to moderate in
severity. No patients treated with ambrisentan developed serum
aminotransferase concentrations greater than three-times the upper
limit of the normal range (3xULN) at any time during the 12-week
treatment period, compared to three patients in the placebo groups
(2.3%).
"Since both ARIES trials achieved their primary efficacy endpoint
for all three ambrisentan doses, we conducted the prespecified
analysis of the integrated data generated by ARIES-1 and ARIES-2 to
better understand the dose response for both the primary and secondary
endpoints in these trials and to generate a more robust measure of the
treatment effect of the 5 mg dose, the common dose in the two trials,"
said Dr. J. William Freytag, President and CEO. "The integrated
analysis also enables us to gain a better understanding of the
dose-related incidence of adverse events. This analysis further
reinforces our confidence that ambrisentan has the potential to be a
significant therapeutic advance in the treatment of 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. The trials
were conducted under protocols with identical inclusion and exclusion
criteria. 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. ARIES-1 enrolled 202 patients primarily in
the United States while ARIES-2 enrolled 192 patients primarily in
Europe. Approximately 400 patients are continuing 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 tested
-- 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 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 licensed 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. Myogen 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.
Myogen and GlaxoSmithKline have entered into a global PAH
collaboration 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 licensed ambrisentan
from Myogen for all territories outside of the United States, where
Myogen retains exclusive rights. 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 combined analysis of the Company's ARIES
clinical trials, summary statements relating to the results of the
Company's prior clinical trials of ambrisentan in patients with PAH
and the related extension trials, 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. Even though prospectively defined,
analyses that combine the results of separate trials, including this
analysis, may not be accepted by regulatory agencies. Even though
ambrisentan met the defined safety and efficacy endpoints, regulatory
authorities may not approve it for marketing. If ambrisentan is
approved, the Company may not be able to successfully market it, or
the Company may face post-approval problems that require its
withdrawal 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. If ambrisentan
is approved for marketing, the market size for PAH and the market
acceptance of ambrisentan to treat PAH is uncertain, and ambrisentan
may never be a profitable product. 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 May 3,
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.