Roche and Alnylam announced that the Phase II KARDIA-2 study [NCT05103332] of zilebesiran, an investigational RNAi therapeutic in development for the treatment of hypertension (high blood pressure) - the leading cause of cardiovascular disease worldwide1 - met its primary endpoint. People with mild to moderate hypertension treated with zilebesiran added to a standard of care hypertension medication experienced a clinically and statistically significant reduction in systolic blood pressure at month three. People with mild to moderate pulmonary hypertension treated with zilebesIRan added to a standard of Care hypertension medication experienced a clinically and statistical significant reduction in systolic Blood pressure at month three.

Hypertension, or high blood pressure, is the leading causes of cardiovascular disease worldwide and a major risk for premature mortality. It is a growing global health crisis, responsible for around 10 million deaths worldwide each year. Approximately one in three adults are living with hypertension globally, and there remains a significant unmet medical need given the poor rates of adherence to existing treatments.

Currently, up to 80% of people with hypertension have blood pressure that remains uncontrolled despite the availability of several classes of oral hypertension treatments, leaving them at an increased risk of cardiovascular, cerebrovascular, and renal disease. 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.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.

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. Zilebesiran inhibits the synthesis of AGT in the liver, potentially leading to durable reductions in AGT protein and ultimately, in thevasoconstrictor 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 zilebeiran 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. Zilebesiran Phase II clinical development overview: Study Overview of protocol: KARDIA-1 [ NCT04936035] Evaluated zilebesiran monotherapy in people with mild to moderate hypertension.

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