ISLAMABAD, November 16 (Online): Two promising new clinical trials targeting cholesterol genetics were announced this week at the American Heart Association’s annual conference.
Both drugs, designed to lower unhealthy cholesterol levels, have been shown to be effective and safe, their creators said.
The drugs target people born with a genetic predisposition to high cholesterol, making the user more likely to suffer heart attack and stroke.
Current tools for managing high cholesterol include exercise, diet, and statin medications. These two new drugs will be the first to investigate the genetic cause of high cholesterol.
But neither will hit the market anytime soon, as both will require years of further research before being approved for consumers.
But experts say the results are encouraging.
D., a physician at Kroll Medical Group and Cholesterol Treatment Center in New Jersey and director of the Northeast Lipid Association. “The new studies… are truly a groundbreaking change in the world of cardiovascular medicine,” said Spencer Kroll, MD.
“Although they are in early-stage clinical trials, these studies demonstrate that cholesterol management and cardiovascular disease treatment is a multimodal and individualized process,” Kroll, who was not involved in the research, told Medical News Today. “We are now entering the realm of cholesterol treatment, moving away from one-size-fits-all statin therapy to patient-specific personalized treatments.”
New drug targets cholesterol at the genetic level
One treatment comes from Boston-based Verve Therapeutic and uses a gene editing method called base editing.
It is given via IV and targets the PCSK9 gene, which is associated with high levels of LDL, also known as “bad cholesterol.”
The researchers explain that the drug makes a small change in PCSK9, limiting its ability to raise cholesterol. In theory, a one-time treatment should last a lifetime, although subjects have only been followed for six months so far.
The first study had only 10 participants and was intended to examine the safety of the drug. Most subjects did not receive doses large enough to make a measurable difference in their cholesterol levels, but they survived the experiment without significant side effects or health problems.
Verve Therapeutic researchers reported giving higher doses to three subjects whose LDL levels fell by more than half.
All of the study participants had a genetic condition called heterozygous familial hypercholesterolemia, which is characterized by high cholesterol levels from birth. Many people with this condition have a heart attack when they reach their 30s or 40s.
Interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback, Dr. “Although this first-in-human trial was very small, it showed a large reduction in LDL levels in a few patients,” said Cheng-Han Chen. California Medical Center, which was not involved in the research.
“Most importantly, the study was successful in showing that the ‘base editing’ technique could work on the liver in humans,” Chen told Medical News Today. “These are the first clinical results showing proof of concept in humans, but much more research is needed before it can be used on a larger scale.”
Research on this drug has not yet been published in a peer-reviewed journal.
New cholesterol drug targets lipoproteins
A second, potentially breakthrough therapy aimed at lowering cholesterol was also announced at the conference.
This targets a type of cholesterol-related protein called lipoprotein. People with high lipoprotein(a) levels have a high risk of fat and cholesterol accumulation in their arteries. Lipoprotein attaches to LDL cholesterol, potentially causing plaque buildup.
This condition is genetic, and researchers have noted that exercise, diet, and statins have little effect on lipoprotein levels.
The research team, funded by pharmaceutical company Eli Lilly, used a drug called lepodisiran, which helps block production at the level of a key protein component of the lipoprotein(a) particle.
The second study was also small; It was done on only 48 adults with high levels of lipoprotein(a) in the United States and Singapore.
Researchers reported that the drug was found to be safe with no significant side effects. They said a single dose of the drug also reduced lipoprotein(a) levels by 94% over the course of a year.
Researchers noted that 64 million adults in the United States have high lipoprotein levels.
More research needed on new cholesterol drugs
Experts not involved in the study told Medical News Today that although the study results are promising, both treatments have a long way to go.
“While this small proof-of-concept study of VERVE-101 is extremely interesting, I anticipate that hundreds, if not thousands, of similar patients will need to be treated to demonstrate the safety and effectiveness of this treatment before the Food and Drug Administration or any other agency will need to treat it before The Ohio State University Wexner Medicine “International regulatory bodies will consider approval,” said Dr. Wesley Milks, a cardiologist at the Center who specializes in cardiovascular disease prevention, including the management of lipid disorders.
There are potential downsides to treating people at the genetic level, Milks said.
“With an intervention that theoretically results in permanent DNA editing, the irreversibility of such treatment may be troubling to many patients and healthcare providers,” he said. “I would want to be absolutely confident that there will be an extremely low risk of off-target or other undesirable genetic defects as a result of receiving this CRISPR gene editing therapy before recommending it to my own patients.”
In addition, chief medical officer of weight loss program Found and former medical director of the American Board of Obesity Medicine, Dr. Rekha Kumar said the treatments may have other drawbacks when they are finally approved.
“This is new because of the mechanism of action of these two new potential drugs, but both are far from daily use,” Kumar said. “Both target specific genetic abnormalities related to cholesterol metabolism, making this an important development as we move toward personalized treatments for cholesterol metabolism disorders.”
“Drugs become very expensive when personalized, so we are talking about the high cost of a drug that treats a specific population,” he added. “Oftentimes, many people do not know that they have these diseases or that they have access to the right care to get tested for these genetic abnormalities.
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