KARDIA-2 Study: Zilebesiran Enhances Standard Hypertension Treatment

Alnylam Pharmaceuticals, a pioneering company in RNAi therapeutics, has reported positive outcomes from the KARDIA-2 Phase 2 clinical trial. The study assessed the impact of a single subcutaneous dose of zilebesiran, an RNAi therapeutic aimed at angiotensinogen (AGT), when combined with three different standard antihypertensive treatments. The trial demonstrated significant reductions in systolic blood pressure, with zilebesiran showing a favorable safety profile as an adjunct to standard care.
The primary endpoint of the study was met, with zilebesiran contributing to a mean reduction of up to 12.1 mmHg in 24-hour systolic blood pressure as measured by ambulatory blood pressure monitoring when added to treatments such as indapamide, amlodipine, or olmesartan. At the six-month mark, zilebesiran continued to show significant reductions in office systolic blood pressure, even when rescue antihypertensives were introduced.
Dr. Akshay Desai, a heart failure expert at Brigham and Women’s Hospital, highlighted the challenges in managing hypertension with current oral treatments due to patient adherence issues and clinical inertia. He expressed optimism about zilebesiran's potential to address these challenges and transform clinical practice with its semiannual dosing regimen.
The study's detailed results revealed that zilebesiran, when paired with indapamide or amlodipine, led to substantial reductions in both 24-hour mean systolic blood pressure and office systolic blood pressure sustained up to six months. The results were less pronounced when zilebesiran was combined with the maximum dose of olmesartan. The study also showed that fewer patients treated with zilebesiran required additional antihypertensive medication compared to those on a placebo.
In terms of safety, zilebesiran was generally well-tolerated. The incidence of adverse events was comparable between the zilebesiran and placebo groups, with most events being mild and resolving within a short period. There were no fatalities or discontinuations due to adverse events during the study's double-blind phase.
Alnylam is advancing its KARDIA program, which includes the recently initiated KARDIA-3 Phase 2 study to evaluate zilebesiran's efficacy in high cardiovascular risk patients with uncontrolled hypertension despite current antihypertensive treatments. The company aims to disrupt the treatment landscape for hypertension, which affects over a billion people globally and contributes to significant morbidity and mortality.
Zilebesiran operates through RNAi technology, which involves the use of small interfering RNA to silence disease-causing genes. This approach has shown promise in the development of new therapies for a range of diseases. Alnylam, which has been a leader in RNAi therapeutics since its inception, has a portfolio of both commercial and investigational products targeting various diseases.
The company's commitment to innovation is reflected in its "Alnylam P5x25" strategy, which focuses on delivering impactful medicines for both rare and common diseases. Alnylam's management, along with Dr. Desai, discussed the KARDIA-2 results in a webcast investor event, emphasizing the potential of zilebesiran as a novel treatment option for hypertension.