DENVER, April 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 completion of patient enrollment
in DAR-201, the company's Phase 2b trial of darusentan in patients with
resistant systolic hypertension.
"The completion of patient enrollment in the darusentan resistant
hypertension trial is the first of several important clinical trial milestones
for Myogen this year," said J. William Freytag, President and Chief Executive
Officer of Myogen. "In addition to completing this trial on July 8th and
reporting its preliminary results one to two months thereafter, we also expect
to report results from our two pivotal Phase 3 trials of enoximone capsules in
patients with advanced chronic heart failure in the middle of the year and
results from one of our two pivotal Phase 3 trials of ambrisentan in patients
with pulmonary arterial hypertension by the end of the year."
About DAR-201
The primary objective of this Phase 2b randomized, double-blind,
placebo-controlled trial is to determine if darusentan is effective in
reducing systolic blood pressure in patients with resistant systolic
hypertension. Patients were eligible for enrollment in this trial if they had
a systolic blood pressure greater than or equal to 140 mmHg despite treatment
with full doses of three anti-hypertension medications, one of which was a
diuretic. A total of 115 patients were randomized to darusentan or placebo at
approximately 30 investigative sites. Patients undergo forced titration every
two weeks through 10, 50, 100 and 150 mg of darusentan or placebo until the
target dose of 300 mg once a day is achieved. The treatment period is
10 weeks followed by a 2-week drug withdrawal period.
About Resistant Hypertension
Hypertension affects approximately 50 million individuals in the United
States and approximately one billion worldwide. Despite the availability and
use of several classes of drugs (diuretics, ACE inhibitors, angiotensin
receptor blockers, beta-blockers, calcium channel blockers, central alpha
receptor agonists, peripheral antagonists and vasodilators) to treat
hypertension, a significant percentage of these patients cannot achieve blood
pressures within the recommended range, a condition referred to as "resistant
hypertension."
The "Seventh Report of the Joint National Committee on Prevention,
Detection, Evaluation and Treatment of High Blood Pressure" (JNC7) defines
resistant hypertension as "the failure to achieve goal blood pressure in
patients who are adhering to full doses of an appropriate three-drug regimen
that includes a diuretic." According to JNC7, a systolic blood pressure of
less than 140 mmHg and a diastolic blood pressure of less than 90 mmHg are
recommended for patients with hypertension and no other serious conditions.
For patients with serious conditions, such as diabetes and chronic renal
disease, target systolic and diastolic blood pressures are more stringent -- a
systolic blood pressure goal of less than 130 mmHg and a diastolic blood
pressure goal of less than 80 mmHg.
Clinical studies in hypertension have shown that diastolic blood pressure
can be controlled to a goal of 90 mmHg in approximately 90% of hypertensive
patients. However, in these same studies, guideline-recommended goals for
systolic blood pressure were achieved in only 60% of patients, even when
multi-drug regimens were utilized. Clinical studies have also shown that
hypertension in patients with diabetes or chronic renal disease is
consistently more difficult to manage, requiring treatment with a multi-drug
regimen. Despite intensive, multi-drug therapy, however, only 50% of patients
with diabetes or chronic renal disease reach traditional blood pressure goals,
with even fewer reaching the more stringent blood pressure goals now
recommended by JNC7. Moreover, data from a study conducted in a hypertension
specialist clinic revealed that more than half of the diabetic patients
examined required treatment with three or more antihypertensive drugs and only
22% of the patients studied achieved systolic blood pressure of less than
130 mmHg.
We believe a considerable number of individuals with hypertension,
especially those with diabetes or chronic renal disease, are at risk for
significant and progressive cardiovascular and renal complications due
primarily to inadequate control of their systolic blood pressure. As a
result, we believe there is a significant opportunity for a drug that is
capable of lowering blood pressure in this resistant patient population.
About Darusentan
Darusentan is a type-A selective endothelin receptor antagonist (ERA) and
potent inhibitor of endothelin-induced vasoconstriction. Endothelin is a
small peptide hormone that is believed to play 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. Therefore, we believe that agents
that block the detrimental effects of endothelin will provide significant
benefits in the treatment of these conditions. Darusentan is selective for
the ET(A) receptor versus the ET(B) receptor, demonstrates a half-life that
may be suitable for once a day dosing and has demonstrated a significant
anti-hypertensive effect in patients with moderate essential hypertension. As
an ERA, darusentan affects blood pressure by a mechanism different than other
approved antihypertensive drugs.
In 2000, the original sponsor of darusentan evaluated the safety and
efficacy of darusentan as monotherapy in 392 patients with moderate essential
hypertension (Stage II) in a Phase 2 randomized, double-blind,
placebo-controlled, dose-ranging trial titled the HEAT study. The primary
endpoint of the trial was change in sitting diastolic blood pressure after six
weeks of treatment. Changes in systolic blood pressure and pulse rate were
secondary endpoints.
The results of this study demonstrated that darusentan produced
statistically significant and clinically meaningful reductions in diastolic
and systolic blood pressures in a dose-dependent manner. The mean
placebo-corrected change from baseline in systolic blood pressure was
-6.0 mmHg on 10 mg, -7.3 mmHg on 30 mg and -11.3 mmHg on 100 mg darusentan
after six weeks of treatment. Significant reductions in diastolic blood
pressure were also observed (-3.7, -4.9 and -8.3 mmHg, for the three dose
groups, respectively). Heart rate remained unchanged in all groups. Headache
was the most commonly reported adverse event, with no relevant difference
among placebo and active treatment groups. Flushing and peripheral edema were
seen in a dose-dependent fashion in the darusentan treatment groups. There
were no treatment-related elevations in liver function tests in the study.
This study was conducted in a different patient population than is being
studied in DAR-201 and there can be no assurance that comparable results will
be observed in DAR-201 as those reported in the HEAT study.
About Myogen
Myogen currently markets one product (Perfan(R) I.V.) 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 advanced chronic heart failure, ambrisentan for the
treatment of patients with pulmonary arterial hypertension and darusentan for
the treatment of patients with resistant systolic 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 our 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
reporting of results from the company's Phase 2b trial of darusentan and
pivotal Phase 3 trials of oral enoximone and 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.
Among other things, the projected timing of a public announcement relating
to the company's clinical trial results may be affected by difficulties or
delays in completion of patient treatment, data collection and data analysis.
In addition, the company's operating and financial results may be affected by
difficulties or delays in its clinical trials, competition from other
pharmaceutical and biotechnology companies, regulatory developments involving
current and future products, its effectiveness at managing its financial
resources and its ability to successfully develop and market its current
products. Results from earlier clinical trials, including the HEAT trial, are
not necessarily predictive of future clinical results. Preliminary results
may not be confirmed upon full analysis of the detailed results of a trial.
Delays in 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's
product candidates, including darusentan, ambrisentan 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 the company'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 product 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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