A single, under-the-skin dose of the investigational RNA-interference drug zilebesiran lowered blood pressure when added to standard therapy in adults whose hypertension remained uncontrolled, according to results from the global Phase 2 KARDIA-2 trial of 663 participants published in JAMA.
Researchers led by Queen Mary University of London reported results from the Phase 2 KARDIA-2 trial, a global study of adults whose blood pressure was not adequately controlled on a standard antihypertensive medicine.
In the trial, 663 adults were randomized to receive a single subcutaneous dose of zilebesiran or placebo on top of their existing therapy. The study found that adding zilebesiran produced larger reductions in blood pressure than standard treatment alone, with statistically significant reductions in ambulatory systolic blood pressure at three months.
Dr. Manish Saxena, clinical co-director of the William Harvey Clinical Research Centre at Queen Mary University of London and a hypertension specialist at Barts Health NHS Trust, said the long duration of effect could help address persistently low blood-pressure control rates worldwide and reduce the risk of complications such as heart attacks and strokes.
Zilebesiran is designed to lower blood pressure by using RNA interference to reduce production of angiotensinogen in the liver, a key component of the renin–angiotensin system involved in blood-pressure regulation.
The research was funded by Alnylam Pharmaceuticals. Queen Mary University of London said Barts Health NHS Trust was the top-enrolling center in Europe.
Researchers said further studies are planned, including the Phase 2 KARDIA-3 trial in people with hypertension and established cardiovascular disease or at high cardiovascular risk. They also said a large global cardiovascular outcomes trial is planned to examine whether the approach can reduce major cardiovascular events, including stroke and cardiovascular death.
The findings were published in JAMA.
