Roche and Alnylam report positive topline results from the Phase II KARDIA-2 study in people with hypertension, demonstrating clinically significant blood pressure reductions with zilebesiran when added to standard of care - Seite 2

The Phase II KARDIA-2 trial results will be presented as a late-breaking abstract at the 2024 American College of Cardiology Annual Scientific Session (6-8 April 2024, Atlanta, Georgia, USA). The KARDIA-2 results build on the positive Phase II KARDIA-1 [NCT04936035] data, presented at the congress of the American Heart Association Scientific Sessions in November 2023, and published in JAMA in February 2024.^9,10 Roche and Alnylam have now initiated the global Phase II KARDIA-3 study [NCT06272487] designed to evaluate the efficacy of zilebesiran when added to two or more hypertension medications in people with uncontrolled hypertension at high cardiovascular risk.

About the KARDIA-2 study¹¹
The Phase II KARDIA-2 trial is a randomised, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of zilebesiran, when added to a standard of care, in adults with mild-to-moderate hypertension. This global, multicentre trial enrolled 672 adults with hypertension. Patients who met all inclusion/exclusion criteria during a screening period were randomised into three different cohorts to receive open-label therapy with olmesartan, amlodipine or indapamide as their protocol-specified background hypertension medication during a run-in period of at least four weeks. Following the run-in period, eligible patients were randomised 1:1 to receive zilebesiran 600 mg or placebo in addition to their protocol-specified background hypertension medication for six months.

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

About zilebesiran
Zilebesiran is an investigational, subcutaneously administered RNAi therapeutic targeting angiotensinogen (AGT) in development for the treatment of hypertension in high unmet need populations. AGT is the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), a cascade which has a demonstrated role in blood pressure regulation and its inhibition has well-established antihypertensive effects. Zilebesiran inhibits the synthesis of AGT in the liver, potentially leading to durable reductions in AGT protein and ultimately, in the vasoconstrictor angiotensin (Ang) II. Zilebesiran utilises Alnylam's Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables infrequent subcutaneous dosing with increased selectivity and the potential to achieve tonic blood pressure control demonstrating consistent and durable blood pressure reduction throughout a 24-hour period, sustained up to six months after a single dose of zilebesiran. The safety and efficacy of zilebesiran have not been established or evaluated by the U.S. Food and Drug Administration, European Medicines Agency, or any other health authority. Zilebesiran is being co-developed and co-commercialised by Roche and Alynlam.