Alnylam’s KARDIA-1 trial meets primary endpoint in hypertension

Alnylam has announced positive results from its Phase II study of zilebesiran for the treatment of patients with hypertension and high cardiovascular risk.

The US-based company has confirmed that the KARDIA-1 trial met its primary endpoint, seeing a systolic blood pressure reduction across a 24-hour period at month three. It also met its secondary endpoints, including a demonstration of durable efficacy over six months.

The results were presented at the American Heart Association (AHA) Scientific Sessions, which was held in Philadelphia, US, on 11 November.

The Phase II study is a randomised, double-blind, placebo-controlled study that was carried out at sites across the US, UK and Canada. The trial enrolled 394 adults with untreated hypertension or who were on stable therapy with one or more anti-hypertensive medications.

Patients were randomised to one of five treatment arms of a 150mg dose once every six months, a 300mg dose every three and six months, and a 600mg dose every six months, or a placebo.

According to the presentation, zilebesiran demonstrated an encouraging safety profile, with adverse effects reported in 6.7% of patients in the placebo group and 3.6% of patients in the zilebesiran cohort.

Alnylam’s zilebesiran programme lead Simon Fox said: “The totality of the data presented at the American Heart Association Scientific Sessions gives us confidence in zilebesiran’s potentially differentiated profile and its ability to transform the treatment landscape for patients with uncontrolled hypertension who are at high risk of future cardiovascular events.”

GlobalData’s Pharmaceutical Intelligence Centre shows that there are more than 10,000 competing drugs marketed for the indication of hypertension, making it a relatively crowded market, with total sales in the indication estimated at around $17.6bn in 2022. This figure is expected to rise to $19.1bn by 2026.

GlobalData is the parent company of Clinical Trials Arena.

George Bakris, director of the American Heart Association Comprehensive Hypertension Centre, said: “These KARDIA-1 results are impressive, showing that in a diverse group of patients with mild-to-moderate hypertension, zilebesiran can safely achieve clinically significant reductions in systolic blood pressure and tonic blood pressure control administered subcutaneously with either quarterly or bi-annual dosing.”