Positive Phase I results for RNAi therapeutic in hypertension

Patient using blood pressure monitor

Alnylam Pharmaceuticals has revealed results from its Phase I study of zilebesiran, an investigational RNAi therapeutic targeting liver-expressed angiotensinogen (AGT) in development for the treatment of hypertension.

The results are published in the New England Journal of Medicine (NEJM).

The key data showed that compared to placebo, zilebesiran was associated with dose-dependent reductions in serum AGT, achieving tonic blood pressure control with consistent and durable blood pressure reduction throughout a 24-hour period, sustained up to six months after single doses of ≥200mg of zilebesiran.

Zilebesiran also demonstrated an acceptable safety profile supporting continued clinical development; the most frequent treatment-related adverse events were mild, transient injection-site reactions.

“Despite the availability of effective antihypertensive treatments, nearly half of patients with hypertension fail to achieve guideline-recommended blood pressure targets, leaving them at residual risk for myocardial infarction, stroke, kidney disease progression, and mortality,” said Akshay Desai, the lead author of the manuscript and Director of the Cardiomyopathy and Heart Failure Program in the Advanced Heart Disease Section of the Cardiovascular Division at Brigham and Women’s Hospital.

“For clinicians, the challenge in optimising treatment of hypertension is frequently compounded by poor adherence to prescribed medical therapy and substantial variability in blood pressure between office visits and over the 24-hour cycle.

“In this context, the data we have published in NEJM are exciting, suggesting the potential role for zilebesiran to treat hypertension in a novel way via a novel, subcutaneously administered gene silencing approach to hypertension.”

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