Gileads’ Hypertension Drug Shows Promise

Gilead’s DAR-311 (DORADO) Phase III trial evaluating its once-daily oral endothelin receptor antagonist (ERA) darusentan as an add-on treatment for resistant hypertension, achieved positive results. 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 or placebo 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.

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 from baseline 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.

Ambulatory blood pressure monitoring (ABPM) performed at week 14 revealed highly significant reductions from baseline in 24-hour SBP and DBP in patients treated with darusentan. Reductions in ambulatory SBP were maintained throughout the 24-hour monitoring period and there were no significant changes in heart rate.

According to guidelines, SBP of less than 140 mmHg is recommended for patients with hypertension and no other serious conditions. For patients with diabetes and CKD, target SBP is more stringent, with a goal of less than 130 mmHg. In DAR-311, more than half of patients treated with darusentan achieved goal blood pressure, as compared to approximately one quarter of patients receiving placebo.