A breakthrough may be on the horizon for millions of people suffering from high blood pressure – the leading cause of heart attacks and strokes – in the form of a six-monthly injection instead of daily medication for the condition.
Known as zilebesiran, the jab targets a key hormone produced by the liver, reports The Independent.
The injection, produced by US-based Alnylan Pharmaceuticals, has recently undergone trials in Britain, during which experts at Queen Mary University of London recruited 107 patients with hypertension, of whom 80 were given a shot of zilebesiran under their skin and 32 received a placebo with no active ingredients.
Five of the 32 patients who were on the placebo were later given zilebesiran.
Initial analysis showed that volunteers on zilebesiran experienced a significant drop in systolic blood pressure that lasted up to six months.
Systolic blood pressure – the pressure in your arteries when your heart beats – was lowered by more than 10mmHg at least a 200mg dose and 20mmHg at the highest of 800mg.
The drop can take a patient’s high blood pressure into a safer range.
Despite high blood pressure being difficult to treat due to its fluctuations across a day, zilebesiran resulted in a consistent drop over 24 hours.
The medication prevents the production of angiotensin, a hormone that narrows blood vessels and causes blood pressure to rise, said the researchers in their paper, which was reported in the New England Journal of Medicine.
“Overall, these preliminary data… support the potential for further study of quarterly or twice-yearly administration of zilebesiran as a treatment for patients with hypertension.”
Professor David Webb, who led the trial in Edinburgh, added: “This is a potentially major development in hypertension. There has not been a new class of drug licensed for the treatment of high blood pressure in 17 years.
“This novel approach leads to a substantial reduction in blood pressure, both by day and night, that lasts for around six months after a single injection.”
Study details
Zilebesiran, an RNA interference therapeutic agent for hypertension
Akshay Desai, David Webb, Jorg Taubel, Sarah Casey, Yansong Cheng, Gabriel Robbie,
Don Foster, Stephen Huang, Sean Rhyee, Marianne Sweetser, and George Bakris.
Published in the New England Journal of Medicine on 23 July 2023
Abstract
Background
Angiotensinogen is the sole precursor of angiotensin peptides and has a key role in the pathogenesis of hypertension. Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis.
Methods
In this phase 1 study, patients with hypertension were randomly assigned in a 2:1 ratio to receive either a single ascending subcutaneous dose of zilebesiran (10, 25, 50, 100, 200, 400, or 800 mg) or placebo and were followed for 24 weeks (Part A). Part B assessed the effect of the 800-mg dose of zilebesiran on blood pressure under low- or high-salt diet conditions, and Part E the effect of that dose when co-administered with irbesartan. End points included safety, pharmacokinetic and pharmacodynamic characteristics, and the change from baseline in systolic and diastolic blood pressure, as measured by 24-hour ambulatory blood-pressure monitoring.
Results
Of 107 patients enrolled, 5 had mild, transient injection-site reactions. There were no reports of hypotension, hyperkalemia, or worsening of renal function resulting in medical intervention. In Part A, patients receiving zilebesiran had decreases in serum angiotensinogen levels that were correlated with the administered dose (r=−0.56 at week 8; 95% confidence interval, −0.69 to −0.39). Single doses of zilebesiran (≥200 mg) were associated with decreases in systolic blood pressure (>10 mm Hg) and diastolic blood pressure (>5 mm Hg) by week 8; these changes were consistent throughout the diurnal cycle and were sustained at 24 weeks. Results from Parts B and E were consistent with attenuation of the effect on blood pressure by a high-salt diet and with an augmented effect through co-administration with irbesartan, respectively.
Conclusions
Dose-dependent decreases in serum angiotensinogen levels and 24-hour ambulatory blood pressure were sustained for up to 24 weeks after a single subcutaneous dose of zilebesiran of 200 mg or more; mild injection-site reactions were observed.
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