HQ Team
September 5, 2023: Australian researchers have discovered an oral drug to treat excess bad cholesterol in the blood, a condition that raises the risk of heart attack and stroke.
The researchers demonstrated the success of Muvalaplin — the first oral drug developed to target lipoprotein(a) or Lp(a) — in the first human clinical trial, by effectively lowering levels by up to 65% when taken daily during during the 14-day trial period.
It works by disrupting the ability of Lp(a), a genetic form of cholesterol, to form in the body. There is currently no cure or approved treatment for lowering Lp(a) levels.
Lipoproteins are a type of protein that transports cholesterol through the blood.
About 25% of people worldwide have the genetic version of bad cholesterol and lifestyle changes such as diet and exercise do not help in curbing the levels in the blood.
Larger-phase clinical trials
The phase I early trial was undertaken in collaboration with Cleveland Clinic and Eli Lilly. The drug will now continue into larger phase clinical trials.
It may also have the potential to be used in the treatment of other vascular and valve diseases.
Lp(a) is similar to LDL cholesterol, sometimes called ‘bad cholesterol’, but is more sticky, increasing the risk of blockages and blood clots in arteries, leading to heart diseases and stroke.
Common LDL-lowering drugs such as statins don’t have the same lowering effect on Lp(a). The genetic protein was discovered nearly 60 years ago.
Lipoprotein aphaeresis is the only therapy approved by the Food and Drug Administration for lowering LDL in limited number of patient categories.
‘No tools in kit’
Prof Stephen Nicholls, cardiologist and Director of Monash University’s Victorian Heart Institute and the Victorian Heart Hospital at Monash Health, led the research and trial, presented at the European Society of Cardiology Congress in Amsterdam recently.
“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,” Professor Nicholls said.
“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.”
“Lp(a) is essentially a silent killer with no available treatment, this drug changes that.”
Lipoproteins are classified into two groups. High-density lipoprotein (HDL) cholesterol, is considered “good” while low-density lipoprotein (LDL) cholesterol, is considered “bad.”
Thickening of arteries
Excessive LDL cholesterol can lead to atherosclerosis — where cholesterol builds up to form plaques on the inside walls of arteries, making it hard for blood to pump through.
The amount of Lp(a) in a person’s system is determined by their genetic history and ethnicity. African Americans are at an increased risk for high Lp(a) compared to other ethnic groups.
“Lp(a) forms when an LDL particle binds to the protein Apo(a),” Prof Nicholls said.
“Muvalaplin essentially blocks that binding from happening in the liver and therefore prevents the formation of Lp(a). It would provide an oral option for the treatment of patients with high Lp(a) levels to reduce their risk of heart disease.”
It would take more than five years for the drug to be on the market, according to the study published in the journal JAMA.
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