– Study Met the Primary Endpoint Demonstrating Clinically Significant Systolic Blood Pressure Reductions at Month 3 When Zilebesiran Was Added to a Diuretic, Calcium-Channel Blocker or Angiotensin Receptor Blocker –

– Zilebesiran Demonstrated an Encouraging Safety and Tolerability Profile When Added to Standard of Care Antihypertensives –

– Study Results Support Potential for Biannual Dosing of Zilebesiran –

– Full Study Results to Be Presented as a Late-Breaking Clinical Trial at the 2024 American College of Cardiology Annual Scientific Session on April 7 –

– Alnylam and Roche Also Announce Initiation of the KARDIA-3 Phase 2 Study in Patients at High Cardiovascular Risk with Uncontrolled Hypertension Despite Standard of Care Antihypertensive Treatments –

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the KARDIA-2 Phase 2 study of zilebesiran, an investigational RNAi therapeutic targeting liver-expressed angiotensinogen (AGT) in development for the treatment of hypertension, met the primary endpoint showing that zilebesiran resulted in clinically and statistically significant additive, placebo-adjusted reductions in 24-hour mean systolic blood pressure (SBP) at Month 3 as measured by ambulatory blood pressure monitoring (ABPM) in each of three independent patient cohorts receiving the standardized background therapies of either a thiazide-like diuretic (indapamide), calcium channel blocker (amlodipine) or angiotensin receptor blocker (olmesartan). Zilebesiran demonstrated an encouraging safety and tolerability profile when added to these standard of care antihypertensives. The Company believes these findings support further development.

“We are thrilled that a single dose of zilebesiran achieved clinically significant, additional reductions in systolic blood pressure when administered to patients who are not adequately controlled with commonly prescribed antihypertensives,” said Simon Fox, Ph.D., Vice President, Zilebesiran Program Lead at Alnylam. “These KARDIA-2 results, showing durable additional levels of blood pressure reduction on top of what is achieved by standard of care first-line antihypertensives with an encouraging safety profile, reinforce our confidence in zilebesiran’s differentiated profile. We look forward to sharing the full KARDIA-2 data as a late-breaking clinical trial at the upcoming American College of Cardiology Annual Scientific Session.”

The KARDIA-2 Phase 2 study is a randomized, double-blind (DB), placebo-controlled study designed to evaluate the efficacy and safety of zilebesiran, when added to standard of care antihypertensive medications, in adults with mild-to-moderate hypertension. This global, multicenter study enrolled 672 adults with hypertension. Patients who met all inclusion criteria and none of the exclusion criteria during a screening period were first randomized into three different cohorts to receive open-label therapy with olmesartan, amlodipine or indapamide as their protocol-specified background antihypertensive medication during a run-in period of at least four weeks. Following the run-in period, eligible patients were randomized 1:1 to receive 600 mg zilebesiran or placebo in addition to their protocol-specified background antihypertensive medication for six months.

The primary endpoint is the change from baseline in mean SBP at Month 3, assessed by 24-hour ABPM. Additional endpoints include the change in 24-hour mean SBP after six months of treatment assessed by ABPM, change in office SBP at Month 3 and Month 6, and change in diastolic blood pressure (DBP) measured by ABPM and office blood pressure at Month 3 and Month 6. Safety will be assessed throughout the study.

Alnylam and Roche today also announced the initiation of the global KARDIA-3 (NCT06272487) Phase 2 study, a randomized, DB, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of zilebesiran used as an add-on therapy in adult patients with high cardiovascular risk and uncontrolled hypertension despite treatment with two to four standard of care antihypertensive medications. Patients with estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73m2 will be enrolled to cohort A, and patients with eGFR 30 to