Twice-Yearly Injection Shows Promise For High Blood Pressure Treatment In Global Trial

An international phase 2 clinical trial involving 663 patients across eight countries tested a twice-yearly injection of zilebesiran for treating high blood pressure. The Kardia 2 study found the drug, which targets a liver protein involved in blood pressure regulation, significantly lowered systolic blood pressure compared to standard treatments, researchers reported.

The Kardia 2 study, a phase 2 randomized clinical trial, enrolled 663 patients from eight countries who had poorly controlled hypertension despite standard treatments, according to researchers involved in the trial. Participants received a subcutaneous injection of zilebesiran every six months alongside existing medications such as amlodipine, indapamide, or olmesartan. The primary goal was to assess whether this twice-yearly injection could reduce systolic blood pressure more effectively than standard care alone.

Nearly one-third of hypertension patients struggle to stabilize their blood pressure, and the trial targeted this group by adding zilebesiran as an adjunct therapy.

Results from the trial showed that patients treated with zilebesiran experienced a greater and more consistent reduction in systolic blood pressure compared to those receiving only oral medications, according to data published by the study team. The single injection was found to sustain its blood pressure-lowering effect for up to six months, potentially addressing common adherence challenges, as nearly half of patients discontinue oral antihypertensive treatments within one year, the researchers noted.

Zilebesiran works by using small interfering RNA (siRNA) technology to inhibit the liver production of angiotensinogen (AGT), a protein that plays a central role in blood pressure regulation through vasoconstriction, according to the drug’s developers, Roche and Alnylam Pharmaceuticals. By targeting AGT, zilebesiran acts upstream in the renin-angiotensin pathway, preventing blood vessel constriction and reducing hypertension. Mid-stage trial results were published in the New England Journal of Medicine earlier this year, confirming the sustained systolic reductions observed in Kardia 2.

Professor Sir Nilesh Samani, medical director at the British Heart Foundation and one of the study’s lead investigators from Queen Mary University of London and Barts Health NHS Trust, said the trial’s findings suggest that twice-yearly dosing could improve blood pressure control and potentially lower risks of heart attacks and strokes. The British Heart Foundation reports that approximately 15 million adults in the U.K., or 28% of the population, have hypertension, with half of those affected not effectively treated. Samani noted that if phase 3 trials confirm these results, zilebesiran could replace daily pills for some patients.

Dr. Amit Raj, director of Plexus Cardiac Care, highlighted that therapies like zilebesiran act at the source of hypertension by targeting angiotensinogen production, which may reduce the overall cardiovascular burden. He emphasized the potential benefits for patients who are non-responsive or inconsistent with current treatments. Luke Laffin, M.D., of the Cleveland Clinic, who led a related trial testing tonlamarsen—a monthly injectable siRNA targeting the same protein—said ongoing research is needed for patients with severe hypertension who struggle with daily medication adherence.

The related Kardinal phase 2 trial, led by the Cleveland Clinic and involving 206 U.S. patients, tested tonlamarsen administered monthly in adults with systolic blood pressure between 135 and 170 mmHg despite taking two to five antihypertensive drugs. Presented on March 28, 2026, at the American College of Cardiology meeting and published in the Journal of the American College of Cardiology, the trial showed that single or five monthly doses reduced angiotensinogen levels and lowered blood pressure similarly to zilebesiran.

Following the promising results from Kardia 2, zilebesiran is advancing to phase 3 trials, according to Roche and Alnylam officials. These late-stage studies will further evaluate the drug’s efficacy and safety in a larger population. The injectable approach aligns with a growing trend toward long-acting therapies in cardiovascular care, similar to recently approved cholesterol-lowering injections recommended by the National Institute for Health and Care Excellence (NICE) in the U.K.

If phase 3 trials confirm the benefits, twice-yearly injections of zilebesiran could become an important addition to hypertension treatment, particularly for patients who have difficulty adhering to daily oral regimens or who remain uncontrolled despite multiple medications. The development represents a potential shift in managing a condition that remains poorly controlled worldwide despite the availability of effective oral therapies.