Press release
Genentech and Alnylam Advance Zilebesiran Into Global Phase III Cardiovascular Outcomes Trial for People With Uncontrolled Hypertension
– Phase III trial informed by comprehensive KARDIA data set generated through three Phase II studies: KARDIA-1, KARDIA-2 and KARDIA-3 – – In the Phase II
About this update from Alnylam Pharmaceuticals, Inc.
[{"type":"text","content":"\n– Phase III trial informed by comprehensive KARDIA data set generated through three Phase II studies: KARDIA-1, KARDIA-2 and KARDIA-3 –\n\n\n– In the Phase II KARDIA-3 study, presented today as a late breaker at the European Society of Cardiology Congress 2025, zilebesiran demonstrated clinically meaningful reductions in office systolic blood pressure at month three with continuous control through month six –\n\n\n– Zilebesiran, a potential best-in-disease RNAi antihypertensive with twice-yearly subcutaneous dosing, demonstrated encouraging safety when combined with two or more antihypertensives –\n\n\n– Phase III cardiovascular outcomes trial expected to be initiated by the end of the year –\n\n\n SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--\nGenentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) and Alnylam (Nasdaq: ALNY) today announced the decision to initiate a Phase III cardiovascular outcomes trial (CVOT) to evaluate the ability of zilebesiran, an RNAi therapeutic, to reduce the risk of major adverse cardiovascular events in patients with uncontrolled hypertension. This decision was informed by the comprehensive KARDIA Phase II program, including KARDIA-1, KARDIA-2 and the most recent KARDIA-3 study evaluating the efficacy and safety of zilebesiran in patients with uncontrolled hypertension and high cardiovascular (CV) risk, on two to four standard of care antihypertensives. In particular, KARDIA-3 aimed to define the patient population to be investigated in the Phase III CV outcomes trial.\n\n\nResults of KARDIA-3 showed a single dose of zilebesiran (300 mg every six months, subcutaneous injection) resulted in clinically meaningful placebo-adjusted reductions of office systolic blood pressure (SBP) in all comers at the month three primary endpoint (-5.0 mmHg; p=0.0431) with sustained benefits out to month six (-3.9 mmHg; 95% CI: [-8.5, 0.7]). There were no additional benefits of the 600 mg dose at month three (-3.3 mmHg; p=0.1830) or month six (-3.6 mmHg; 95% CI: [-8.2, 1.0]). The overall KARDIA-3 study did not meet the pre-specified definition for statistical significance, because of a multiplicity statistical testing approach. However the study met the aim of identifying the patient population that could potentially benefit the most from zilebesiran and also showed encouraging safety and clinically mea...