ALNYLAM PHARMACEUTICALS, INC.
The data were presented as a late-breaking clinical trial at the 2024
The study achieved its primary endpoint showing statistically significant and clinically meaningful additive, placebo-adjusted systolic blood pressure (SBP) reductions of up to 12.1 mmHg at month three (assessed by 24-hour ambulatory blood pressure monitoring, ABPM) when adding zilebesiran to SOC antihypertensives including a thiazide-like diuretic (indapamide), calcium channel blocker (amlodipine) or angiotensin receptor blocker (olmesartan).
In addition, the study met its key secondary endpoint evaluated at month three, with a single dose of zilebesiran demonstrating clinically significant additive reductions in office SBP across all three independent cohorts. Zilebesiran also showed significant, sustained placebo-adjusted SBP reductions at month six when added to indapamide and amlodipine, despite the addition of rescue antihypertensives at month three. Overall, zilebesiran demonstrated clinically significant additive reductions in time-adjusted and placebo-adjusted office systolic blood pressure at month six across all three study cohorts, including the maximum dose of olmesartan.
'The KARDIA Phase II studies add to a growing body of evidence supporting the potential for zilebesiran to sustain lower blood pressure with twice-yearly dosing in combination with standard of care medicines,' said
Hypertension, or high blood pressure, is the leading cause of cardiovascular disease worldwide and a major risk for premature mortality.1 Hypertension represents a growing global health crisis, responsible for around 10 million deaths worldwide each year.2 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.3 Currently, up to 80% of people with hypertension have blood pressure that remains uncontrolled despite the availability of several classes of oral hypertension treatments; such individuals remain at an increased risk of cardiovascular, cerebrovascular, and renal disease.4-8
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
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 first randomised into three different cohorts to receive open-label therapy with olmesartan (maximum dose), 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 with elevated SBP were randomised 1:1 in a blinded manner to receive one dose of zilebesiran 600 mg SC or placebo in addition to their protocol-specified background hypertension medication for six months.
As outlined in the study protocol, after three months of treatment, all patients were permitted to receive rescue antihypertensives as needed based on rescue response criteria. Across all cohorts, a higher percentage of placebo-treated patients required treatment with rescue antihypertensives compared to zilebesiran-treated patients.
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
About hypertension
More than one billion adults are living with hypertension worldwide, which is a major risk factor for cardiovascular disease and premature mortality.4 Early effects of hypertension can include subtle target organ damage such as left-ventricular hypertrophy and cognitive dysfunction.12,13 Over time, uncontrolled hypertension can lead to cardiovascular disease including stroke (ischaemic and haemorrhagic), coronary artery disease, heart failure, peripheral artery disease, chronic kidney disease and end-stage renal disease, dementia, and Alzheimer's disease.5-8
There remains a significant unmet medical need, as poor rates of adherence to daily medications can result in inconsistent blood pressure control and an increased risk for stroke, heart attack, and premature death.3 In particular, there are a number of high unmet need settings where novel approaches to hypertension warrant additional development focus, including patients with high cardiovascular risk.14
About Roche
Founded in 1896 in
In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the fifteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work.
Contact:
Dr.
Tel: +41 61 68-75284
Email: bruno.eschli@roche.com
Dr.
Tel: +41 61 68-88027
Email: sabine.borngraeber@roche.com
Tel: +1 650 225 3217
Email: kalm.loren@gene.com
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