Breakthrough drug targets life-threatening 'bad cholesterol'

Tuesday, 26 September, 2023

Breakthrough drug targets life-threatening 'bad cholesterol'

Researchers have trialled a new drug that is claimed to provide world-first treatment for lipoprotein(a), a largely genetic form of cholesterol that increases the risk of heart attack and stroke. High levels of lipoprotein(a), or Lp(a), impact one in five Australians, with no approved treatment currently on the market.

Lp(a) is similar to LDL cholesterol, sometimes called ‘bad cholesterol’, but is more sticky, increasing risk of blockages and blood clots in arteries. Common LDL-lowering drugs such as statins don’t have the same lowering effect on Lp(a), and Lp(a) is also difficult to control through diet, exercise and other lifestyle changes due to its largely genetic nature.

Although Lp(a) was discovered nearly 60 years ago, there still aren’t any widely accessible treatments available to lower levels and reduce cardiovascular risk. Researchers have been working on a targeted solution to treat elevated Lp(a) for the past decade, but advancements so far have been in difficult-to-administer injection-based therapies that are not yet on the market.

“When it comes to treating high Lp(a), a known risk factor for cardiovascular disease, our clinicians currently have no effective tools in their kit,” said Professor Stephen Nicholls, Director of the Monash Victorian Heart Institute and The Victorian Heart Hospital.

Nicholls has been leading landmark research into muvalaplin — the first oral drug ever developed to target Lp(a), which works by disrupting the ability for Lp(a) to form in the body. The results of a recent first-in-human phase 1 trial, which were presented at the European Society of Cardiology Congress in Amsterdam and published in JAMA, show that the drug effectively lowered Lp(a) levels by up to 65% in healthy participants.

“This drug is a game changer in more ways than one,” Nicholls said. “Not only do we have an option for lowering an elusive form of cholesterol, but being able to deliver it in an oral tablet means it will be more accessible for patients.”

The trial was undertaken in collaboration with Cleveland Clinic and Eli Lilly, with the drug now set to continue into larger-phase clinical trials. It may also have potential to be used in the treatment of other vascular and valve diseases.

“Lp(a) is essentially a silent killer with no available treatment,” Nicholls said. “This drug changes that.”

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