A Therapy to Reduce Lipoprotein(a) Levels

The research and development community is ever in search of the next statin drug, and a way to reduce lipoprotein(a) levels looks very much like an alternative statin. Statins reduce the amount of cholesterol carried by LDL particles in the bloodstream. Lipoprotein(a) is a carrier of cholesterol, like LDL, and research has shown that high levels correlate with the development of atherosclerotic lesions, as is the case for LDL-cholesterol. That being so, one can't be all that optimistic that a treatment to reduce lipoprotein(a) will actually do much for disease risk. Statins reduce risk of stroke and heart attack resulting from atherosclerosis by, at most, and arguably, 20% or so - levels of cholesterol carried in the bloodstream are not the most important input to the disease process. A quarter of humanity still dies from these conditions in the environment in which everyone who can take statins is taking statins. Statins continue to make a great deal of profit for pharmaceutical companies, however, so developing something that looks very much like a statin? That sounds great to the powers that be.

Findings from a phase 1 trial show that a single dose of an experimental therapy, lepodisiran, produced greater than 94% reductions in blood levels of lipoprotein(a), a key driver of heart disease risk, with the results lasting for nearly a year. Lipoprotein(a), often shortened to just Lp(a), is made in the liver and has similarities to LDL, also known as low-density lipoprotein or "bad cholesterol." Unlike other types of cholesterol particles, Lp(a) levels are 80-90% genetically determined. The structure of the Lp(a) particle causes the accumulation of plaque in arteries which greatly increases the risk of heart attacks and strokes.

Although effective therapies exist to reduce the risk of heart disease by lowering LDL cholesterol and other lipids, currently there are no approved drug treatments to lower Lp(a). Since Lp(a) levels are determined by a person's genes, lifestyle changes (diet or exercise) have no effect. In the trial, participants who received an injection of lepodisiran had lipoprotein(a) levels reduced by the top dose as much as 96% within two weeks and maintained levels more than 94% below baseline for 48 weeks. The drug is a small interfering RNA (siRNA) therapeutic that blocks the messenger RNA needed to manufacture a key component of lipoprotein(a) in the liver.

Link: https://www.eurekalert.org/news-releases/1007716