Alnylam to Advance Zilebesiran into Global Phase 3 Cardiovascular Outcomes Trial

- Phase 3 Trial Informed by KARDIA-3 Phase 2 Study Results Presented as a Late-Breaking Abstract at the European Society of Cardiology Congress 2025 -

- Zilebesiran Demonstrated Clinically Meaningful Reductions in Office Systolic Blood Pressure in Patients with Uncontrolled Hypertension and High Cardiovascular Risk at Month 3 Primary Endpoint, with Continuous Control Through Month 6 -

- Zilebesiran Displayed Encouraging Safety When Combined with Two or More Antihypertensives -

- Results Support Biannual Dosing Regimen and Inform Phase 3 Trial Design: Trial Expected to Initiate by Year-End 2025 -

- Alnylam to Host Webcast Investor Event on August 30, 2025, at 1:00 pm ET (7:00 pm CEST) -

CAMBRIDGE, Mass.--(BUSINESS WIRE)--

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced plans to initiate a Phase 3 cardiovascular outcomes trial (CVOT) to evaluate the potential of zilebesiran to reduce the risk of major adverse cardiovascular events. This decision is informed by results from the comprehensive KARDIA Phase 2 program, including KARDIA-3 results presented today as a late-breaking abstract at the European Society of Cardiology (ESC) Congress in Madrid, Spain. Zilebesiran is an investigational subcutaneously administered RNAi therapeutic which, in the KARDIA Phase 2 program, has shown reductions in blood pressure by targeting liver-expressed angiotensinogen (AGT), the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), which plays a key role in blood pressure regulation and impacts cardiovascular and renal health.

KARDIA-3, the third Phase 2 study in the KARDIA program, evaluated the efficacy and safety of zilebesiran in patients with uncontrolled hypertension and high cardiovascular (CV) risk on two or more background antihypertensives. The study met the objective of informing the design, patient population, and dose for the global Phase 3 CVOT, ZENITH (ZilebEsiraN CardIovascular OuTcome Study in Hypertension).

Results of KARDIA-3 showed a single 300 mg dose of zilebesiran resulted in clinically meaningful, placebo-adjusted reductions of office systolic blood pressure (SBP) at the Month 3 primary endpoint (-5.0 mmHg; p=0.0431) with sustained benefits out to Month 6 (-3.9 mmHg; 95% CI: -8.5, 0.7). There were no additional benefits of the 600 mg dose at Month 3 (-3.3 mmHg; p=0.1830) or Month 6 (-3.6 mmHg; 95% CI: -8.2, 1.0). The statistical testing of change in office SBP at the Month 3 primary endpoint was controlled for multiplicity, which required both doses to have a p-value of