– Zilebesiran Met Primary Endpoint Demonstrating Up to 16.7 mmHg Placebo-Adjusted Reduction of 24-Hour Mean Systolic Blood Pressure at Three Months of Treatment –

– Study Met Key Secondary Endpoints Showing Consistent and Sustained Reductions of Systolic Blood Pressure and Durable Tonic Blood Pressure Control Through Month 6 –

– Data Support Quarterly or Biannual Dosing –

– Zilebesiran Demonstrated an Encouraging Safety and Tolerability Profile in Adult Patients with Mild-to-Moderate Hypertension –

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced positive results from the KARDIA-1 Phase 2 study of zilebesiran, an investigational RNAi therapeutic targeting liver-expressed angiotensinogen (AGT) in development for the treatment of patients with hypertension and high cardiovascular risk. The study results were presented during the American Heart Association (AHA) Scientific Sessions being held in Philadelphia, Pennsylvania from November 11-13, 2023. The Company previously announced positive topline results from the KARDIA-1 study in September 2023.

The KARDIA-1 study achieved its primary endpoint, with single doses of zilebesiran demonstrating clinically significant reductions in 24-hour mean systolic blood pressure (SBP) measured by ambulatory blood pressure monitoring (ABPM) at Month 3 across all doses, with the 150 mg, 300 mg, and 600 mg doses achieving placebo-adjusted reductions of 14.1 mmHg, 16.7 mmHg, and 15.7 mmHg, respectively (all p-values less than 0.0001). The study also met key secondary endpoints across all doses, including demonstration of durable efficacy out to 6 months. At the 150 mg Q6M, 300 mg Q6M, 300 mg Q3M, and 600 mg Q6M doses, zilebesiran showed placebo-adjusted reductions in 24-hour mean SBP measured by ABPM of 11.1 mmHg, 14.5 mmHg, 14.1 mmHg, and 14.2 mmHg, respectively, at Month 6 (all p-values less than 0.0001). Zilebesiran demonstrated an encouraging safety and tolerability profile that the Company believes supports continued development.

“These KARDIA-1 results are impressive, showing that in a diverse group of patients with mild-to-moderate hypertension, zilebesiran can safely achieve clinically significant reductions in systolic blood pressure and tonic blood pressure control administered subcutaneously with either quarterly or bi-annual dosing,” said Professor George L. Bakris, M.D., Board-Certified Hypertension Specialist and Director of the American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine. “I continue to be encouraged and optimistic that zilebesiran has the potential to become not only a novel treatment for hypertension but also a transformative therapy to lower cardiovascular and renal risk in patients with hypertension, an area where new and innovative therapies are desperately needed.”

KARDIA-1 Study Results

The KARDIA-1 Phase 2 study is a randomized, double-blind, placebo-controlled, multi-center global dose-ranging study designed to evaluate the efficacy and safety of subcutaneously administered zilebesiran as monotherapy in adults with mild-to-moderate hypertension.

The study enrolled 394 adults representing a diverse patient population, of which more than 40% were female and nearly 25% were Black, with untreated hypertension or who were on stable therapy with one or more anti-hypertensive medications. Any patients taking prior antihypertensive medications completed at least a two- to four-week wash-out before randomization. Patients were randomized to one of five treatment arms: 150 mg zilebesiran once every six months (Q6M); 300 mg zilebesiran Q6M; 300 mg zilebesiran once every three months (Q3M); 600 mg zilebesiran Q6M; or placebo.

The primary endpoint was the change from baseline in 24-hour mean SBP at Month 3, assessed by ABPM. Key secondary endpoints in this study include additional measures of blood pressure reduction at Month 3 and Month 6, and the proportion of patients achieving treatment response criteria at Month 6, defined as 24-hour mean ambulatory SBP