Between 20-25% of people worldwide have high levels of lipoprotein(a), more commonly known as Lp(a) — a genetic form of low-density lipoprotein (LDL) cholesterol, also known as “bad” cholesterol.
Because Lp(a) is genetic, lifestyle changes like diet and exercise that may benefit other types of cholesterol do not help. There is currently no cure or approved specific treatment for lowering Lp(a) levels.
Now, researchers from Monash University’s Victorian Heart Institute and Victorian Heart Hospital, in Australia, have found that an experimental oral medication developed to target Lp(a) was able to lower its levels by more than half during a first-in-human phase 1 clinical trial.
This study was recently published in the journal JAMA.
Lipoproteins are a type of protein that transports cholesterol through the blood. There are two main types of lipoproteins:
- high-density lipoprotein (HDL) cholesterol, considered “good”
- low-density lipoprotein (LDL) cholesterol, considered “bad.”
Although the body needs some cholesterol for certain functions, too much LDL cholesterol can lead to atherosclerosis — a condition where cholesterol builds up to form plaques on the inside walls of arteries, making it hard for blood to pump through.
Lp(a) is a form of LDL cholesterol that is “stickier” than other types, making it easier for the build-up to occur and arteries to become blocked.
The amount of Lp(a) in a person’s system is determined by their genetic history and ethnicity. For example, African Americans are at an increased risk for high Lp(a) compared to other ethnic groups.
Having a high level of Lp(a) can increase a person’s risk for cardiovascular diseases such as coronary heart disease and stroke.
In the current study, researchers conducted a clinical trial to assess an experimental medication for lowering Lp(a) levels called muvalaplin.
“Genetic and population studies show us that high Lp(a) levels (are associated) with a high risk of heart disease,” Dr. Stephen Nicholls, cardiologist and director of Monash University’s Victorian Heart Institute and the Victorian Heart Hospital at Monash Health and lead author of this study, told Medical News Today when asked why it was important to have therapies available for Lp(a).
“As much as 20% of the population have high levels. We don’t currently have specific therapies that lower levels, which may be important in the prevention of heart disease,” he noted.
Through the study, Dr. Nicholls and his team looked at how well the drug worked, as well as its safety and tolerability in humans.
“Lp(a) forms when an LDL particle binds to the protein Apo(a),” he explained.
“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.”
– Dr. Stephen Nicholls
Muvalaplin lowers Lp(a) by up to 65%
For this phase 1 clinical trial, Dr. Nicholls and his team recruited 114 healthy participants of different genders and ethnic backgrounds.
The purpose of this study was to assess the safety and tolerability of muvalaplin, its pharmacokinetics (what happens to the drug in the body), as well as indicators of the drug’s effect on the target, Lp(a).
Participants either received a single dose of muvalaplin, an ascending dose where the amount taken was increased over time, or a placebo for 14 days.
At the end of the study, researchers found that participants who received muvalaplin lowered their Lp(a) levels by as much as 65% when taken daily over the 14-day period.
In terms of safety and tolerability by humans, scientists reported muvalaplin was not associated with any tolerability concerns or clinically significant adverse effects.
The most commonly reported side effects from study participants included headache, back pain, fatigue, diarrhea, abdominal pain, and nausea.
When asked how quickly we may see muvalaplin approved as a drug for doctors to prescribe, he said it will need to continue in larger and longer clinical trials and would not be available for more than five years.
Underrecognized heart disease risk factor
After reviewing this study, Dr. Cheng-Han Chen, an interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, not involved in the research, told MNT this research was definitely a step in the right direction.
“Lp(a) is a very hot topic right now in heart disease,” he explained. “There’s a lot of studies investigating how we can improve a patient’s health outcomes by covering that drug.”
“There [are] other agents that are in clinical trials right now — they’re all injections,” Dr. Chen continued. “So you can imagine that if you’ve got a choice, a patient would rather get pills than injections. It’s a big step in the right direction in terms of getting people a therapy that they could just take a pill rather than an injection.”
MNT also spoke with Dr. Yu-Ming Ni, a board-certified cardiologist and lipidologist at MemorialCare Heart and Vascular Institute at Orange Coast Medical Center in Fountain Valley, CA, not involved in the research. Dr. Ni was also happy to hear about a new potential medication for Lp(a).
“Lp(a) is an underrecognized risk factor for cardiovascular disease,” he said. “It’s largely genetically inherited and it might explain the propensity for certain families to have higher rates of heart disease, particularly at younger ages.”
“There’s really not much you can do to lower your Lp(a),” Dr. Ni continued. “It’s something you’re born with and it doesn’t change very much over time. That’s why I think it’s important that we recognize it because it’s kind of an underlying factor that if you’re not really aware of it, it sets your baseline for risk.”
How can you lower Lp(a) levels?
Because Lp(a) is genetic, lifestyle modifications that may help lower other types of LDL cholesterol are not as effective.
Right now, the only Food and Drug Administration (FDA) approved therapy for lowering Lp(a) is lipoprotein apheresis. This process physically removes lipoproteins from the blood and is only available for people with certain Lp(a) levels and other risk factors.
Researchers are currently looking at PCSK9 inhibitors as a possible treatment for lowering Lp(a) levels.
There are also currently a number of drug candidates for lowering Lp(a) going through clinical trials.
Dr. Chen said as medical professionals consider Lp(a) as the worst type of LDL cholesterol and it is genetic, he was happy to hear researchers were expanding their research on this topic.
“What really needs to be done is bigger trials to make sure that it’s safe for larger populations besides the one they studied,” he said when asked what he would like to see in the next research steps for muvalaplin.
“We know right now the more Lp(a) you have, the more heart disease events you’re going to have. What we all want to know is if we lower the Lp(a), does it lower the risk of having a heart disease event. That’s what we’re all really excited to see the results of,” Dr. Chen added.
Dr. Ni emphasized the importance of doctors screening for Lp(a) in people who are at high risk.
“I screen for Lp(a) pretty frequently with my patients,” he told us. “I know that there are doctors that don’t do that as much and I try to encourage […] other doctors to be thinking about screening for Lp(a) in high-risk patients. And it’s not something you get with traditional lab testing, so I do think it’s a factor that is very important.”
“Some studies have suggested that [Lp(a)] can be attributed to a two to three-times higher risk for heart disease in certain patients at a high Lp(a), so I do think it’s a very important lab test that we should be doing frequently,” Dr. Ni added.