Melbourne researchers are helping expand options for people with high cholesterol that puts them at risk of heart attack or stroke, including world-first drugs for potentially deadly conditions.
Monash University and Monash Health are collaborating on projects that aim to develop the first effective drug for two types of high cholesterol that until now have had no effective treatment.
The trials include:
KRAKEN, a randomised phase 2 trial of Muvalaplin, the first oral drug that targets Lipoprotein(a) particles
BROOKLYN, which is investigating the safety and efficacy of Obicetrapib in patients with a form of genetic high cholesterol called Heterozygous Familial Hypercholesterolemia (HeFH)
Monash Victorian Heart Institute and Victorian Heart Hospital Director, Professor Stephen Nicholls, has just presented on KRAKEN and BROOKLYN at the American Heart Association Conference in Chicago.
The Kraken trial - A world first treatment for bad cholesterol's 'evil cousin'
Led by Professor Nicholls, Kraken is a phase 2 trial of Muvalaplin, a world-first oral drug to target Lipoprotein(a) - a largely genetic form of high cholesterol that affects one in five people globally and has no approved treatment.
Lipoprotein(a), also known as Lp(a), is similar to LDL cholesterol (sometimes called 'bad cholesterol') but stickier, increasing risk of blockages and blood clots in arteries. High levels of Lp(a) increase the risk of heart attack and stroke.
As it is largely genetic, Lp(a) is difficult to control through diet, exercise and other lifestyle changes.
So far, the trial has shown that Muvalaplin effectively lowers levels by up to 70 per cent using traditional assays and up to 85.8 per cent using a novel assay, by disrupting the ability of Lp(a) to form in the body.
Lp(a) was discovered nearly 60 years ago. Research over the past 10 years has resulted in several injection-based therapies but they are difficult to administer and not yet on the market.
"Lp(a) is essentially a silent killer with no available treatment; this drug changes that," Professor Nicholls said. "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."
"This drug is a game-changer in more ways than one. 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 Brooklyn trial – New hope for families at risk of a silent genetic killer
Brooklyn is a phase 3 trial for Obicetrapib, a therapy for those with familial hypercholesterolemia (FH), a genetic condition causing high cholesterol.
In Australia, FH affects an estimated 1 in 250 people, or roughly 100,000 individuals. Many individuals with FH are unable to reach and maintain cholesterol targets with standard treatments.
Obicetrapib lowered LDL ('bad') cholesterol by 36.3 per cent at day 84 and 41.5 per cent at day 365, compared to a placebo. It was observed to be generally well-tolerated with safety results comparable to the placebo.
"It's important to have options for people in this high-risk group as they have persistently high cholesterol levels that often don't fully respond to standard treatments including statins and ezetimibe," Professor Nicholls said.
"The findings of this study are significant as nearly 4 out of 5 patients reached the cholesterol target for primary prevention in FH and 1 in 2 got lower."
"This genetic disorder is often underdiagnosed and undertreated, with less than 10 per cent of those affected identified, meaning that many people and their families may unknowingly live with an increased risk of premature cardiovascular disease."
Read the full paper in JAMA: Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial. DOI: 10.1001/jama.2024.24017
