Aussie researchers expand high cholesterol treatments with game-changing data unveiled on global stage

Monash University and Monash Health are collaborating on two clinical trials to develop the first effective drug treatments for two types of high cholesterol that have previously lacked effective options.

The trials, which aim to address Lipoprotein(a) (Lp(a)) and familial hypercholesterolemia (FH), are being led by Professor Stephen Nicholls, Director of the Monash Victorian Heart Institute and Victorian Heart Hospital. He presented the results of the KRAKEN and BROOKLYN trials at the American Heart Association Conference in Chicago, showcasing the promising potential of these therapies.

The KRAKEN trial, a phase 2 study funded by Eli Lilly, focuses on Muvalaplin, an innovative oral drug that targets lipoprotein(a), a largely genetic form of high cholesterol that affects one in five people globally and has no approved treatment.

“Most medications being developed to lower Lp(a) are injectable. Muvalaplin is the first oral agent being developed to lower Lp(a) levels and acts by disrupting the formation of the Lp(a) particle,” said Professor Nicholls.

The results from the KRAKEN trial are promising. Compared to a placebo, Muvalaplin reduced Lp(a) levels by up to 70% using the traditional blood test and by up to 85.5% using the more advanced intact Lp(a) particle test. In fact, 97% of participants achieved Lp(a) levels lower than 125 nmol/L, measured by the intact particle test, while 82% of participants achieved this using the traditional test.

Additionally, Muvalaplin was shown to lower apoB, one of the two major proteins that make up Lp(a), by as much as 16%, without causing notable changes in levels of high-sensitivity C-reactive Protein (hsCRP), a marker for heart attack and stroke risk.

“We were encouraged by the degree of Lp(a)-lowering in these patients who are most likely to benefit from its use and by the safety and tolerability,” said Professor Nicholls. “While Muvalaplin appears to be an effective approach to lowering Lp(a) levels, we still need to study whether Lp(a) lowering will result in fewer heart attacks and strokes.”

Meanwhile, the BROOKLYN trial is a phase 3 study focusing on Obicetrapib, a therapy designed to address familial hypercholesterolemia (FH), a genetic condition that leads to high cholesterol. In Australia, FH affects an estimated 1 in 250 people, roughly 100,000 individuals, many of whom cannot effectively control their cholesterol levels with standard treatments.

Obicetrapib demonstrated significant efficacy, reducing LDL (‘bad’) cholesterol by 36.3% after 84 days and 41.5% after one year, compared to a placebo. The drug was generally well-tolerated, with safety results comparable to the placebo group.

“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 explained. “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 patients achieved even lower levels.”

Obicetrapib was first developed by Amgen and shown to be the most potent of the CETP inhibitors for reducing LDL cholesterol levels. NewAmsterdam, a company created by Kastelein and chief executive officer Dr Michael Davidson, acquired rights to the drug and has been pursuing trials ever since.

Professor Nicholls also highlighted a critical issue in FH, saying “This genetic disorder is often underdiagnosed and undertreated, with less than 10% of those affected identified, meaning that many people and their families may unknowingly live with an increased risk of premature cardiovascular disease.”

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