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Positive Top Line Results Reported for Phase 2 Trial Evaluating Darusentan
"These results are particularly gratifying considering that these patients were already on full doses of three antihypertensive medications including a diuretic," commented Michael J. Gerber, M.D., Senior Vice President, Clinical Development and Regulatory Affairs. "To the best of our knowledge, no other antihypertensive agent has ever been shown to have efficacy in this setting. This outcome supports our optimism that darusentan has the potential to improve the treatment options available to physicians trying to manage this complex disorder. We look forward to initiating a Phase 3 program to evaluate darusentan in a larger, international patient population."
The primary objective of this Phase 2b randomized, double-blind, placebo-controlled trial was to determine if darusentan is effective in reducing systolic blood pressure in patients with resistant hypertension. Patients were eligible for enrollment in this trial if they had a systolic blood pressure greater than or equal to 140 mmHg and a diastolic blood pressure greater than 90 mmHg despite treatment with full doses of three anti-hypertensive medications, one of which was a diuretic, and no other compelling conditions. For patients with diabetes and chronic renal disease, systolic and diastolic blood pressures inclusion criteria were more stringent, namely a systolic blood pressure greater than 130 mmHg and a diastolic blood pressure greater than 80 mmHg. A total of 115 patients were randomized to darusentan or placebo at approximately 30 investigative sites in the U.S. Patients underwent forced titration every two weeks through 10, 50, 100 and 150 mg of darusentan or placebo until the target dose of 300 mg once daily was achieved. The treatment period was ten weeks followed by a two 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 alpha antagonists and vasodilators) to treat hypertension, a significant percentage of these patients (20-30% according to recently published data) fail to achieve blood pressures within the recommended range.
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 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.
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 hypertension, pulmonary arterial hypertension, chronic renal disease, coronary artery disease and chronic heart failure. Therefore, the Company believes that agents that block the detrimental effects of endothelin may provide significant benefits in the treatment of these conditions. Darusentan demonstrates high potency, high bioavailability and a half-life we believe is suitable for once daily dosing. In a prior clinical study in patients with moderate essential hypertension, darusentan demonstrated statistically significant and clinically meaningful dose-dependent reductions in systolic and diastolic blood pressures.
Source: Myogen, Inc.