KARDIA-2 Study Shows Zilebesiran Significantly Lowers Blood Pressure with Standard Treatments

Alnylam Pharmaceuticals, a prominent company in the RNAi therapeutics field, has reported positive findings from the KARDIA-2 Phase 2 clinical trial of zilebesiran, a novel treatment for hypertension. The study showed significant reductions in systolic blood pressure when zilebesiran was combined with standard antihypertensive medications such as diuretics, calcium-channel blockers, or angiotensin receptor blockers. The drug was well-tolerated and demonstrated an encouraging safety profile, supporting its continued development.

The KARDIA-2 trial was a randomized, double-blind, placebo-controlled study that involved 672 adults with mild-to-moderate hypertension. Participants received zilebesiran or a placebo alongside their existing antihypertensive treatment. The primary outcome measure was the change in mean systolic blood pressure at three months, assessed through ambulatory blood pressure monitoring. Zilebesiran was found to provide additional, clinically significant reductions in blood pressure on top of standard treatments.

Simon Fox, Vice President and Zilebesiran Program Lead at Alnylam, expressed enthusiasm for the results, highlighting the drug's potential to offer a new approach to managing high blood pressure, particularly for patients who do not achieve adequate control with existing medications. The full data from the KARDIA-2 study is set to be presented at the 2024 American College of Cardiology Annual Scientific Session.

Additionally, Alnylam and Roche have initiated the KARDIA-3 Phase 2 study, which will evaluate zilebesiran's efficacy and safety in patients with high cardiovascular risk and uncontrolled hypertension, despite standard treatments. This study will involve patients with different levels of kidney function, providing further insight into zilebesiran's potential impact on a broader patient population.

Zilebesiran works by targeting angiotensinogen (AGT), a key component in the Renin-Angiotensin-Aldosterone System (RAAS), which plays a crucial role in blood pressure regulation. By inhibiting AGT synthesis in the liver, zilebesiran could lead to sustained reductions in blood pressure. The drug utilizes Alnylam’s ESC+ GalNAc-conjugate technology, which allows for infrequent dosing and the potential for consistent blood pressure control over an extended period.

Hypertension affects over one billion people globally, with a significant number remaining uncontrolled despite available treatments. The development of new therapeutic approaches like zilebesiran could address the substantial unmet medical need, particularly for patients with poor medication adherence or those at high cardiovascular risk.

RNAi therapeutics, like zilebesiran, represent an innovative approach to disease treatment by silencing specific genes involved in disease pathways. This method has the potential to revolutionize patient care, offering new hope for individuals with genetic and other diseases.

Alnylam Pharmaceuticals, founded in 2002, has been at the forefront of RNAi therapeutic development, with several commercial products already on the market. The company continues to innovate and expand its pipeline, aiming to deliver transformative medicines for both rare and common diseases.