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Investigational RNAi Drug Lowers Blood Pressure in Phase I Study

An RNA interference therapy for hypertension may decrease serum angiotensinogen and blood pressure levels, findings from a Phase I study suggest. In a multi-part, multicenter study funded by Alnylam Pharmaceuticals, researchers from the US and UK aimed to assess the safety, study the pharmacokinetic and pharmacodynamic characteristics, and examine the antihypertensive efficacy of zilebesiran, an investigation RNAi agent designed to bind to and reduce the levels of hepatic angiotensinogen mRNA. They enrolled 107 patients with hypertension into the study, with patients in part A receiving a single ascending dose of zilebesiran or placebo, and patients in parts B and E receiving zilebesiran alongside a certain diet or another hypertension treatment, respectively. As the researchers report in the New England Journal of Medicine, patients receiving zilebesiran experienced declines in serum angiotensinogen levels as well as in blood pressure, and only reported mild injection site reactions. The researchers further note that patients in parts B and E — part D is ongoing and part C was removed from the protocol — indicated that the treatment could be attenuated by a high-salt diet and augmented by simultaneous irbesartan treatment. "Overall, these preliminary data regarding efficacy and safety support the potential for further study of quarterly or twice-yearly administration of zilebesiran as a treatment for patients with hypertension," the researchers report.