A novel therapy being developed by AstraZeneca is showing encouraging results for patients with high-risk hypercholesterolemia, an important risk factor for cardiovascular disease.
A leading cause of death worldwide, approximately 2.6 million people die of cardiovascular disease every year. Hypercholesterolemia – defined as having elevated levels of low-density lipoprotein cholesterol (LDL-C) in the blood – significantly increases the risk of developing the disease. Now research by AstraZeneca has found that its AZD8233 candidate could potentially reduce LDL-C levels, thereby lowering the risk of illness.
AZD8233 works by reducing levels of the PCSK9 gene that increases LDL receptor levels. AstraZeneca’s Regina Fritsche Danielson, SVP and Global Head of Research and Early Development for Cardiovascular, Renal and Metabolism, explains that as well as having this unique way of acting, its method of administration gives it an advantage over other drugs. “AZD8233 is a self-administered subcutaneous injection, which is more convenient than current options that require patients to go to their healthcare professional for administration,” she says.
“Self-administration by patients helps to reduce hospital visits, which are a time and resource burden to patients and healthcare staff. Patients taking on responsibility for their own health has also been shown to improve adherence and promote independence,” Danielson adds.
During Phase IIb of AstraZeneca’s ETESIAN study, three different dose levels (15mg, 50mg, 90mg) of AZD8233 were given to patients with high-risk hypercholesterolemia who were already taking a high-dose statin. Participants were given monthly subcutaneous injections over a 12-week period. All showed reduced LDL-C and PCSK9 levels by week 12 compared to patients who received a placebo.
“PCSK9 is a well validated target and is involved in the regulation of LDL-C,” Danielson says. “More effective LDL-C lowering therapies are needed as more than half of patients with cardiovascular disease at high risk of a major secondary event do not meet their LDL-C goals, despite taking a high-intensity statin,” she adds. “Reducing LDL-C and PCSK9 levels are important to reducing patient risk for coronary heart disease.”
AstraZeneca is confident that AZD8233 has the potential to stand out from its competitors, adding to the company’s leading pipeline that includes mRNA-based therapeutics and cell therapy to tackle the variety of cardiovascular conditions that exist. “Cardiovascular disease is complex and is an umbrella term for different diseases, each with their own complexities and transient molecular changes that underpin the course of disease,” Danielson says.
“In early R&D, advances in understanding disease biology and major innovations in gene editing, cell therapy, translatable models and AI have created a highly fertile scientific environment for research in cardiovascular disease. One approach we are using is investigating unique datasets, using machine learning and artificial intelligence algorithms to start to classify patients into homogenous subclasses, moving towards the possibility of targeting treatments to specific and earlier disease states.”
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