Using novel RNA interference agent, Zilebesiran, to treat hypertension
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Reviewed & translated by Dat Tien Nguyen, B.A, ScM.
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Posted on August 30th, 2023
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Angiotensinogen, as a precursor of angiotensin, plays a key role in the pathophysiology of hypertension. Zilebesiran is a novel RNA interference agent that can bind to hepatic asialoglycoprotein receptors and inhibits synthesis of angiotensinogen in the liver. A study was sponsored by Alnylam Pharmaceuticals to assess the effectiveness and safety of Zilebesiran as a treatment for hypertension.
The phase I clinical trial included 107 participants who have the average age of 53.5 years old with treated or untreated hypertension. To determine the optimal dose of Zilebesiran, the researchers compare the efficacy and safety of different dose levels of the treatment (10, 25, 50, 100, 200, 400, or 800 mg) to the placebo. The treatment and placebo were administered subcutaneously at the beginning of the study. After 8 weeks of surveillance, the researchers found that higher doses of Zilebesiran resulted in more reduction in serum angiotensinogen level, with those who received 200, 400, and 800 mg of Zilebesiran had their serum angiotensinogen level drop below 80% of the baseline level. The lower level of serum angiotensinogen level sustained over 24 weeks; this translated to a significant and long-lasting decrease in both systolic and diastolic blood pressure. In terms of safety, Zilebesiran did not lead to serious hypotension, hyperkalemia or reduced renal function. The effect on blood pressure of the medication can be reverted by having the patients eating a high-sodium diet of more than 5.75 grams of salt per day.
The phase I clinical trial included 107 participants who have the average age of 53.5 years old with treated or untreated hypertension. To determine the optimal dose of Zilebesiran, the researchers compare the efficacy and safety of different dose levels of the treatment (10, 25, 50, 100, 200, 400, or 800 mg) to the placebo. The treatment and placebo were administered subcutaneously at the beginning of the study. After 8 weeks of surveillance, the researchers found that higher doses of Zilebesiran resulted in more reduction in serum angiotensinogen level, with those who received 200, 400, and 800 mg of Zilebesiran had their serum angiotensinogen level drop below 80% of the baseline level. The lower level of serum angiotensinogen level sustained over 24 weeks; this translated to a significant and long-lasting decrease in both systolic and diastolic blood pressure. In terms of safety, Zilebesiran did not lead to serious hypotension, hyperkalemia or reduced renal function. The effect on blood pressure of the medication can be reverted by having the patients eating a high-sodium diet of more than 5.75 grams of salt per day.