Patient Guy received the jab in an earlier clincial trial (Image: Guy Liebenberg/Getty)
A twice-yearly jab could help millions of people better control high blood pressure. A landmark global trial is recruiting 11,000 people to test the jab, after previous smaller studies found it helped to lower readings. Experts hope the new treatment could one day allow some patients to ditch daily pills entirely.
Dr Manish Saxena, national coordinator for the UK and a hypertension specialist at Barts Health NHS Trust, said: “It can be a real game-changer, if it’s successful. The novelty of this treatment is its long duration; giving just one injection every six months could help millions of patients to better manage their condition.”
Around one in three adults have high blood pressure in the UK. It is dubbed a “silent killer” because it typically causes no symptoms.
High blood pressure is a leading cause of heart attacks and strokes, and many patients struggle to bring their readings down into the healthy range. Some end up taking multiple daily pills which can cause side effects including dizziness, headache, fatigue and swollen ankles.
The experimental injection, zilebesiran, is a new type of drug known as small interfering RNA. It works by silencing a gene in the liver.
Dr Saxena, who is also clinical co-director of the William Harvey Clinical Research Centre at Queen Mary University of London, said: “Classically we have used pharmacological drugs in treating high blood pressure, but now we are using RNA interference drugs.
“This is a long-acting therapy — with one injection under the skin every six months you see a sustained blood pressure reduction, rather than taking a pill every day.
“We know that in treating hypertension, one of the big problems is adherence to medication.”
The phase three Zenith trial will involve more than 11,000 people, including hundreds at more than 50 sites across the UK. The first European patient was enrolled at Barts Health earlier this year.
Participants will be offered either 300mg of zilebesiran or a placebo dose every six months, in addition to their standard medications.
The study, which will run for up to five years, will investigate whether the injection reduces patients’ risk of suffering heart attacks, strokes, urgent hospital visits or dying from cardiovascular events.
How does the injection work?
Zilebesiran is a new type of medicine called a small interfering RNA (siRNA) therapy. It works by blocking the liver from making angiotensinogen, a protein used to produce the hormone angiotensin.
Angiotensin causes blood vessels to narrow, raising blood pressure. By reducing the amount of angiotensin produced, zilebesiran helps blood vessels stay more relaxed, lowering blood pressure.
Unlike conventional medicines, siRNA drugs silence the genetic instructions for making angiotensinogen inside liver cells.
As a result, the liver continues producing much less angiotensinogen for months after a single injection, allowing the treatment’s effects to last for longer.
Some patients struggle to control their blood pressure even with multiple drugs (Image: Getty)
If successful, the trial could provide the evidence needed for manufacturers Roche and Alnylam to seek regulatory approval.
Dr Saxena added: “From the results that we have seen so far from previous studies, and the mechanism of action, how it works, the safety profile, we are quite confident that it should do well. But we need to wait for the results to come out.”
A previous international trial involving 663 people with high blood pressure, and whose condition was not being managed well with standard treatment, found that adding the injection helped to significantly reduce readings.
Dr Saxena stressed that he did not want to “rubbish existing treatments”, and that for many patients zilebesiran could be an extra tool alongside their current prescriptions.
However, he hopes the injection could eventually replace daily pills for some patients. He added: “That needs to be seen in longer-term data but it’s quite possible that in some patients who have mild to moderate hypertension, that might be well controlled with the injection alone.
“Some patients might need more add-on therapies as well. That needs to be seen with more data coming out.”
The study is recruiting adults with established cardiovascular disease, or who are aged 55 and over with a high risk of developing it. Participants must be taking at least two antihypertensive medications including a diuretic (water pill).
Dr Saxena added: “The trial is enrolling now, so if anybody is interested they can go on NIHR website and get details about their nearest centre.”
High blood pressure is responsible for more than half of all strokes and heart attacks, according to Blood Pressure UK.
It is also a risk factor for heart disease, kidney disease and vascular dementia and costs the NHS more than £2.1 billion per year.
Dr Pauline Swift, chair of Blood Pressure UK, said: “The development of zilebesiran is an exciting step forward in the treatment of high blood pressure. A six-monthly injection could offer real hope to patients who struggle with daily medication.
“However, as with any new treatment, we still need long-term data to fully understand its safety and effectiveness across diverse patient groups. It’s a promising innovation, but more research is essential before it becomes part of routine care.”
Dr Levi Garraway, Roche’s chief medical officer and head of global product development, said the company believed zilebesiran “has the potential to become a best-in-disease treatment for many patients with uncontrolled hypertension”.
He added: “Its blood pressure-lowering effects and twice-yearly dosing could reduce the risk of serious health complications and death.
“Despite current treatment options, up to 80% of people with hypertension do not achieve adequate blood pressure control putting them at higher risk of cardiovascular events. Therefore, additional treatment options are needed.”
Guy received his first dose of zilebesiran in 2021 and remembers a ‘slight burning’ (Image: Guy Liebenberg)
‘There was a burning feeling, but it was worth it’
Guy Liebenberg took part in an earlier study of zilebesiran after struggling for years to control high blood pressure. He had been prescribed three daily pills before joining the trial. He said: “I felt ill, I didn’t feel good.”
Guy, 72, applied to take part in the research after reading about it in a newspaper. He stopped taking the other medications and received his first injection, alongside just one basic diuretic drug.
Guy said: “My response was very favourable. My blood pressure dropped really, really well, considerably fast.” The former veterinary surgeon saw his readings fall from around 160/100mmHg to around 120/90mmHg.
He remembers that the jab was uncomfortable, but worth it compared to taking more daily pills. Guy explained: “I lay on a table and they injected it into my abdomen. There was a burning feeling.
“The needle going in wasn’t that painful, but it’s when they inject the stuff, you can feel a slight burning under your skin.
“A tablet you might take every 12-24 hours and your blood pressure goes up and down. A six-monthly injection is bringing your blood pressure into a more medically acceptable range all the time. That to me was more favourable.”
Guy, of Brighton, waited for six hours before returning home after each injection, then took regular blood pressure readings. He received three more doses — one of which was a placebo — before the trial ended.
Guy later took part in further blood pressure drug trials. His readings have stabilised since he retired. He added that the injection was “a great thing because you haven’t got the daily worry of taking medication all the time”.
“If you’re going on holiday or travelling you have to remember to take your medication, sometimes before or after you’ve eaten. [The jab is] a hell of a lot easier.”
This story originally appeared on Express.co.uk
