A global clinical trial has commenced to evaluate a twice-yearly injection aimed at improving blood pressure control in millions of patients worldwide. The experimental treatment, called zilebesiran, uses a novel mechanism to silence a gene in the liver responsible for producing a protein that raises blood pressure. Researchers hope this approach will help some patients reduce or even eliminate the need for daily blood pressure medications.
High blood pressure, often referred to as a “silent killer” due to its lack of symptoms, affects approximately one in three adults in the UK and is a leading contributor to heart attacks, strokes, kidney disease, and vascular dementia. Despite the availability of numerous medications, many patients struggle to achieve healthy blood pressure levels, with adherence to daily pills presenting a considerable challenge.
Zilebesiran belongs to a class of drugs known as small interfering RNA (siRNA) therapies. It works by blocking the liver from producing angiotensinogen, a precursor of angiotensin—a hormone that causes blood vessels to narrow, consequently raising blood pressure. By reducing angiotensin levels, the drug helps blood vessels relax, leading to lower blood pressure. Unlike traditional medications, which act on receptors or enzymes, zilebesiran targets genetic instructions, allowing the liver to produce less angiotensinogen for several months following a single injection.
The ongoing phase three Zenith trial aims to enroll over 11,000 participants globally, including several hundred across more than 50 UK sites. Participants will receive either 300 mg of zilebesiran or a placebo injection every six months, in addition to their standard antihypertensive medications. The study will monitor whether the treatment reduces the risk of cardiovascular events such as heart attacks and strokes, as well as hospital admissions and mortality related to high blood pressure. The trial is expected to run for up to five years.
Dr. Manish Saxena, a hypertension specialist and national coordinator for the UK segment of the trial, described the therapy’s long duration of action as a potential "game-changer" in managing hypertension. He noted that the sustained blood pressure reduction after just one injection could address common issues with medication adherence. While Dr. Saxena emphasized that zilebesiran would not replace existing treatments outright, he suggests it might become an additional tool for better blood pressure management, with the possibility that some patients might eventually rely on the injection alone.
Supporters of the trial see zilebesiran as a promising innovation, though experts caution that long-term safety and effectiveness data are still needed across diverse patient populations. Dr. Pauline Swift, chair of Blood Pressure UK, welcomed the development but highlighted the importance of further research before the therapy can be adopted in routine clinical care.
One participant from an earlier study, 72-year-old Guy Liebenberg of Brighton, reported significant improvements in his blood pressure after receiving the injection and reducing other medications. Despite some discomfort during administration, he described the treatment as more convenient than daily pills, particularly when traveling or managing routine medication schedules.
Pharmaceutical companies Roche and Alnylam, which are developing zilebesiran, expressed optimism about the drug’s potential. Roche’s chief medical officer, Dr. Levi Garraway, noted that the therapy’s dosing schedule and blood pressure-lowering effects could reduce the risk of serious health complications and death for many with uncontrolled hypertension. Since up to 80% of patients currently fail to achieve adequate blood pressure control with existing treatments, additional options like zilebesiran are seen as necessary.
As enrollment continues, researchers and patients await results that could reshape the management of high blood pressure, potentially offering a simpler and more effective alternative to current medication regimens.