Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, has announced positive results from the Phase 2 KARDIA-2 trial of zilebesiran, an RNAi therapeutic designed to treat hypertension by targeting liver-expressed angiotensinogen (AGT). The trial met its primary endpoint, showing a clinically and statistically significant reduction in blood pressure when zilebesiran was added to standard antihypertensive medications. These findings support the further development of zilebesiran.
The study involved three independent patient cohorts receiving standard background therapy with a thiazide-like diuretic (indapamide), a calcium channel blocker (amlodipine), or an angiotensin receptor blocker (olmesartan). Zilebesiran demonstrated significant reductions in mean 24-hour systolic blood pressure (SBP) at the third month, as measured by ambulatory blood pressure monitoring (ABPM), when compared to placebo. Additionally, zilebesiran showed a promising safety and tolerability profile when combined with these standard antihypertensive agents.
Dr. Simon Fox, Vice President and Head of the Zilebesiran Program at Alnylam, expressed excitement about the results, highlighting the significant additional reduction in systolic blood pressure achieved with zilebesiran. He emphasized the sustained benefits beyond those of standard first-line antihypertensive agents and the favorable safety profile of zilebesiran.
The Phase 2 KARDIA-2 study involved 672 adults with mild to moderate hypertension and evaluated the efficacy and safety of zilebesiran when added to standard antihypertensive medication. Patients received either zilebesiran or placebo in addition to their baseline antihypertensive medication for six months. The primary endpoint was the change in mean SBP at Month 3, measured by 24-hour ABPM.
Alnylam also announced the initiation of the global Phase 2 trial KARDIA-3, in collaboration with Roche. This trial aims to evaluate the efficacy and safety of zilebesiran as adjunctive therapy in adult patients with high cardiovascular risk and uncontrolled hypertension despite treatment with standard antihypertensive medications.
The initiation of KARDIA-3 marks another step in assessing the potential of zilebesiran in addressing unmet needs in the management of hypertension, particularly in patients with elevated cardiovascular risk.
