Phase III clinical trial evaluating darusentan misses its co-primary efficacy endpoints

Gilead Sciences, Inc. (Nasdaq:GILD) today announced that DAR-312 (DORADO-AC), a Phase III clinical trial evaluating darusentan, the company’s endothelin receptor antagonist (ERA) for the treatment of resistant hypertension, did not achieve its co-primary efficacy endpoints of change from baseline to week 14 in trough sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared to placebo.

DAR-312 is an international Phase III double-blind, placebo- and active-controlled, parallel group trial, in which 849 patients were 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 study was 95 percent powered to detect an 8 mm Hg improvement in SBP and DBP between the darusentan and placebo groups. Reductions in mean trough sitting SBP and DBP from baseline were not statistically significantly different between darusentan and placebo. Darusentan did demonstrate superiority in sitting SBP and DBP when compared to guanfacine at 14 weeks; additionally the study met other secondary endpoints.

“We are disappointed that darusentan did not achieve its primary endpoints in this study,” said Norbert Bischofberger, PhD, Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer. “As a result, we think it would be challenging to define an expedient path forward. We would likely be required to initiate another Phase III study and would rather allocate our resources to other promising research and development opportunities in our pipeline.”