Roche, Alnylam to initiate Phase 3 cardiovascular outcomes trial of zilebesiran

Roche (RHHBY) and Alnylam (ALNY) announced the decision to initiate a Phase 3 cardiovascular outcomes trial to evaluate the ability of zilebesiran, a 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 programme, 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 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,” the companies stated. Results of KARDIA-3 showed that a single dose of zilebesiran resulted in clinically meaningful placebo-adjusted reductions of office systolic blood pressure in all comers at the month three primary endpoint with sustained benefits out to month six. There were no additional benefits of the 600 mg dose at month three or month six. “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 meaningful placebo adjusted reductions in blood pressure,” the companies stated.