Investigational RNA interference therapeutic agent Zilebesiran effective for treatment of hypertension

The key findings of the study are

• A total of 107 patients were enrolled, 5 had mild, transient injection-site reactions. There were no reports of hypotension, hyperkalemia, or worsening of renal function resulting in medical intervention.

• In Part A, patients receiving zilebesiran had decreases in serum angiotensinogen levels that were correlated with the administered dose (r=−0.56 at week 8; 95% confidence interval, −0.69 to −0.39).

• Single doses of zilebesiran (≥200 mg) were associated with decreases in systolic blood pressure (>10 mm Hg) and diastolic blood pressure (>5 mm Hg) by week 8; these changes were consistent throughout the diurnal cycle and were sustained at 24 weeks.

• Results from Parts B and E were consistent with attenuation of the effect on blood pressure by a high-salt diet and with an augmented effect through coadministration with irbesartan, respectively.

The researchers concluded that “Dose-dependent decreases in serum angiotensinogen levels and 24-hour ambulatory blood pressure were sustained for up to 24 weeks after a single subcutaneous dose of zilebesiran of 200 mg or more; mild injection-site reactions were observed.”

Reference: Desai AS, et al "Zilebesiran, an RNA interference therapeutic agent for hypertension" N Engl J Med 2023; DOI: 10.1056/NEJMoa2208391.