Researchers have developed the world’s first oral drug to target a form of cholesterol that has previously been untreatable and is largely caused by genetics, making it difficult to control by way of exercise, diet or other lifestyle factors.
Studies have shown that high levels of lipoprotein(a) or Lp(a), pronounced “L-P-little-A”, increase the likelihood of heart attack or stroke, particularly with familial hypercholesterolemia, an inherited condition characterized by high cholesterol. Lp(a) is a type of low-density lipoprotein (LDL) cholesterol, otherwise known as ‘bad cholesterol,’ but it’s stickier, increasing the risk of blockages and blood clots (atherosclerosis) forming in the arteries.
Commonly used cholesterol-lowering drugs such as statins don’t have the same effect on Lp(a), and because it’s largely caused by genetics, Lp(a) is also difficult to control through diet, exercise and other lifestyle changes. There are no approved medications currently available that target Lp(a).
However, a team led by researchers at Monash University have developed and tested a groundbreaking, world-first oral medication, muvalaplin, that interrupts the body’s ability to form Lp(a).
“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,” says Stephen Nicholls, the study’s lead author. “Lp(a) is essentially a silent killer with no available treatment, this drug changes that.”
Lp(a) is composed of one molecule of an LDL-particle containing apolipoprotein B100 (apo B100) and one molecule of a glycoprotein called apolipoprotein(a), or apo(a). Mulvalaplin disrupts the interaction between apoB100 and apo(a), resulting in lower Lp(a) levels.
The trial enrolled a total of 114 participants; 89 were treated with muvalaplin, and 25 were given a placebo. The trial was conducted in two parts. The first part evaluated the effect of only one dose of muvalaplin in ascending increments, from 1 mg to 800 mg, in healthy participants with a mean age of 29. The second part evaluated the effect of a single daily dose in ascending increments (30 mg to 800 mg) taken over 14 days by healthy participants whose mean age was 32 and who had elevated Lp(a) plasma levels.
Baseline Lp(a) and LDL cholesterol levels were taken at the start of the trial and the effect of muvalaplin on Lp(a) levels observed. The researchers saw reduction in Lp(a) levels from baseline as early as day two with the participants receiving multiple doses. The reduction in Lp(a) was 64% to 65% at doses of 100 mg or more, occurring on days 14 and 15.
Of participants in the single ascending dose group, the most common adverse events were headache (33%), back pain (13%) and fatigue (11%). The multiple ascending dose group reported experiencing headache (31%), diarrhea (20%), abdominal pain (15%), nausea (10%) and fatigue (10%). No deaths or serious adverse events were reported.
The researchers note the study’s limitations, namely that it was a small, phase 1 study. Larger, longer clinical trials in more diverse populations, including those with established cardiovascular disease, will be needed to establish the safety profile of muvalaplin. Additionally, study participants had low-to-moderate elevation of Lp(a) levels; the drug’s target audience would likely include people with greater Lp(a) elevations.
Nonetheless, as the first oral agent specifically developed to lower Lp(a) levels, muvalaplin is a promising development.
“This drug is a game-changer in more ways than one,” Nicholls said. “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 study was published in the journal JAMA Network.
Source: Monash University
This is still significant since as the article states, "Lp(a) is essentially a silent killer with no available treatment, this drug changes that. The trial demonstrated the success of Muvalaplin - the first oral drug ever developed to target Lp(a) - effectively lowering levels by up to 65 per cent. ”
I had thought that Zetia (Ezetimibe) was at least somewhat effective for < Lp(a). But this large meta-study destroys this belief: "Conclusion -- The results of this meta-analysis suggest that ezetimibe treatment does not reduce plasma lipoprotein(a) levels and therefore Lp(a) reduction does not contribute to its therapeutic effect in cardiovascular prevention."
I personally can't. I've been put on them three different times, and each time I suffered both transient and permanent damage to my musculature. Only when 23andMe analyzed my genes did I discover that (no surprise) I'm GENETICALLY predisposed to react badly to statins. So here's the problem. First, dropping cholesterol, no matter by how much, may or may not result in decreased morbidity and mortality -- it could even INCREASE them by destabilizing pre-existing but stable plaque. Second, it sounds like there is at least a 25% chance of fairly serious side effects very much in line with those associated with statins. Not a good look.
I wish the medical community would get off of the cholesterol horse. Cardiovascular disease appears to be yet another inflammatory disease in a long list of inflammatory diseases. It isn't just cholesterol behaving like bacon fat poured into a sink to clog a pipe -- it has chemistry and numerous connections to things like cytokines, vitamin K levels, flow patterns (especially stagnant areas associated with e.g. eddies) in vasculature, chelating metals, and more. Cholesterol per se is the major component of myelin, the "insulating" sheath that wraps our entire nervous system wiring to keep it from shorting out. So OF COURSE reducing cholesterol per se has a raft of side effects -- like headaches in a full third of those treated. They haven't really even begun to look at the unintended consequences of dropping a particular variety of cholesterol by 2/3, and there is no evidence at all that doing so will have any impact on the lifespan of those in the trial. I just think they are off on the wrong track.
Fact is Lipitor nearly killed me causing 'fibromyalgia' causing a lot of muscle pain and made me bed ridden. I was lucky to have figured it out but as it took 5 months to get noticeable, many missed it. Simivastian made me deeply depressed, stopping both for 3 weeks cured me of each pain!
but the use as a primary prevention option seems to be based on the "proven" use as a secondary preventive agent (after a cardiovascular event), rather than noting the number needed to treat for primary prevention versus the potential for myalgia, diabetes and other adverse events that are far higher than the benefit ratio that the routine use of such agents is meant to be providing
eating less or better, doing some exercise, (and choosing genetically well endowed parents) are the clever approaches