Gilead Sciences' data from DAR-311 (DORADO), a phase-III clinical trial evaluating the company's once-daily oral endothelin receptor antagonist (ERA) darusentan as an add-on treatment for resistant hypertension, showed meaningful reductions in blood pressure when darusentan was added to existing antihypertensive regimens in a very difficult-to-treat patient population.
The data was presented at the American Society of Hypertension, Inc (ASH) Twenty-Fourth Annual Scientific Meeting and Exposition (ASH 2009) in San Francisco.
DAR-311 is an international phase-III double-blind, placebo-controlled parallel group trial, in which 379 patients were randomized to receive once-daily doses of darusentan 50 mg (n=81), 100 mg (n=81), 300 mg (n=85) or placebo (n=132) for up to 14 weeks as an add-on to existing antihypertensive regimens. The co-primary efficacy endpoints were change from baseline to week 14 in trough sitting systolic blood pressure (SBP) and trough sitting diastolic blood pressure (DBP). Secondary endpoints included change from baseline in mean 24-hour SBP and DBP and percent of patients reaching SBP goal. Gilead announced top-line results from the study in April.
"Because of the increased risk of a number of life-threatening cardiovascular conditions associated with failure to control blood pressure, including stroke and heart attack, it is essential that new therapeutic approaches be evaluated for treatment of resistant hypertension," said Michael A Weber, professor of Medicine at the Suny Downstate Medical College of Medicine, Brooklyn, New York and lead study author. "These data are important because they showed meaningful reductions in blood pressure when darusentan was added to existing antihypertensive regimens in a very difficult-to-treat patient population."
Baseline demographic and clinical characteristics were comparable across treatment groups. The mean patient age was 62 years old with 39 per cent of patients over age 65. The mean body mass index (BMI) was 32 kg/m2, an indication of obesity. Forty percent of patients were diabetic and 25 per cent of patients had chronic kidney disease (CKD).
In DAR-311, mean reductions in trough sitting SBP from baseline of 16.5 mmHg, 18.1 mmHg, 18.1 mmHg and 8.6 mmHg were observed for the darusentan 50 mg, 100 mg, 300 mg and placebo groups, respectively, after 14 weeks of treatment. Mean reductions in trough sitting DBP from baseline of 10.1 mmHg, 9.9 mmHg, 10.7 mmHg and 5.3 mmHg were observed for the darusentan 50 mg, 100 mg, 300 mg and placebo groups, respectively, after 14 weeks of treatment (p<0.001 for comparison of each darusentan group versus placebo).
Darusentan is an oral, once-daily propanoic-acid class endothelin receptor antagonist (ERA) being investigated in clinical trials as an add-on oral therapy for patients with resistant hypertension.
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need.