April 02, 2009
Phase III Study of Gilead's Darusentan for Resistant Hypertension Meets Primary Endpoints
In the DAR-311 study, reductions in mean trough sitting SBP from baseline of 8.6 mmHg, 16.5 mmHg, 18.1 mmHg and 18.1 mmHg were observed for the placebo, darusentan 50 mg, 100 mg and 300 mg groups, respectively, after 14 weeks of treatment. Reductions in mean trough sitting DBP from baseline of 5.3 mmHg, 10.1 mmHg, 9.9 mmHg and 10.7 mmHg were observed for the placebo, darusentan 50 mg, 100 mg and 300 mg groups, respectively, after 14 weeks of treatment. These results were statistically significant for all darusentan groups (p<0.001).
The most common treatment-emergent adverse event was peripheral edema/fluid retention, which was reported in 17, 32, 36 and 29 percent of patients in the placebo, darusentan 50 mg, 100 mg and 300 mg groups, respectively. Most cases were mild to moderate in severity. Across all study groups, 0 percent, 1.2 percent, 4.9 percent and 5.9 percent of patients in the placebo, darusentan 50 mg, 100 mg and 300 mg groups, respectively, discontinued study drug due to edema. Decreases in hemoglobin (0.19 g/dL, 0.92 g/dL, 0.93 g/dL and 1.08 g/dL in the placebo, darusentan 50 mg, 100 mg and 300 mg, respectively) and decreases in hematocrit (0.89 percent, 2.89 percent, 2.54 percent and 2.88 percent in the placebo, darusentan 50 mg, 100 mg and 300 mg, respectively) were also observed. Liver function test results were comparable between treatment groups. Observed serum aminotransferase concentrations above three times the upper limit of the normal range were reported in three patients, one each in the placebo, 100 mg and 300 mg darusentan groups. One death (sudden cardiac death) occurred during the study; this patient was receiving placebo. Full study results highlighting efficacy and safety will be submitted for presentation at a scientific meeting later this year.
“Failure to control blood pressure elevates the risk of a number of
life-threatening cardiovascular conditions such as stroke, heart attack
and heart failure, suggesting an unmet need for novel antihypertensive
drugs with unique mechanisms of action that can be added to existing
treatment regimens in patients with resistant hypertension. In this
study, more than half of the patients treated with darusentan achieved
goal blood pressure, as compared to approximately one quarter of
patients receiving placebo,” said
Darusentan is an investigational compound and has not yet been determined safe or efficacious in humans.
About the Phase III DORADO Clinical Program
The DORADO program is designed to evaluate the safety and efficacy of darusentan for reducing SBP and DBP in resistant hypertension patients currently treated with full doses of three or more antihypertensive medications, one of which is a diuretic.
DORADO (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).
DORADO-AC (DAR-312) is an international Phase III double-blind, placebo- and active-controlled, parallel group trial, in which approximately 770 patients will be randomized to receive darusentan (titrated to the optimal dose of 50, 100 or 300 mg once daily), an active comparator (guanfacine 1 mg once daily) or placebo. The co-primary endpoints of the trial are the changes from baseline to week 14 in trough sitting SBP and trough sitting DBP, as measured by sphygmomanometry.
For both studies, patients who complete the 14-week assessment period are eligible to enroll in long-term safety studies (DAR-311E and DAR-312E).
Darusentan is a propanoic-acid class endothelin receptor antagonist (ERA) being investigated in clinical trials as an add-on oral therapy for patients with resistant hypertension. Darusentan selectively blocks the endothelin type-A (ETA) receptor, which if activated by endothelin-1 (ET-1), leads to vasoconstriction (narrowing of blood vessels) and cell proliferation. Elevated ET-1 blood concentrations have been reported in some patients with hypertension, including several subgroups of hypertensive patients that have been historically difficult to treat.
About Resistant Hypertension
Resistant hypertension is defined 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 the
Hypertension affects approximately one billion people worldwide. While
the exact number of patients classified as resistant is unknown,
estimates suggest a prevalence of anywhere between two percent and five
percent of hypertensive patients in general practice settings in
This press release includes forward-looking statements, within the
meaning of the Private Securities Litigation Reform Act of 1995, that
are subject to risks, uncertainties and other factors, including risks
related to Gilead’s ability to complete the DORADO-AC clinical trial in
the timelines currently contemplated. In addition, safety and efficacy
data from the DORADO and DORADO-AC clinical trials may not warrant
further development of darusentan for the treatment of resistant
hypertension and feedback from regulatory authorities or results from
clinical trials might result in delays or require additional trials to
be performed. These risks, uncertainties and other factors could cause
actual results to differ materially from those referred to in the
forward-looking statements. The reader is cautioned not to rely on these
forward-looking statements. These and other risks are described in
detail in Gilead’s Annual Report on Form 10-K for the year ended
For more information on Gilead, please call the
1-800-GILEAD-5 (1-800-445-3235) or visit www.gilead.com.
Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Amy Flood, 650-522-5643 (Media)