Tracleer and PPH News Enrollment Completed in Phase 2b Trial of Darusentan in Patients With Resistant Systolic Hypertension
DENVER, April 19 /PRNewswire-FirstCall/ -- Myogen, Inc. (Nasdaq: MYOG - News), 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® 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 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.
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Source: Myogen, Inc.
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