Antibody Leads to Sharp Triglyceride, Cholesterol Drop

(Gerd Altmann, Pixabay)

15 November 2016. An experimental synthetic antibody was shown in a clinical trial to markedly reduce triglycerides and the types of cholesterol that contribute to heart disease. Findings from the trial testing evinacumab, developed by the biopharmaceutical company Regeneron Pharmaceuticals, were presented yesterday by University of Pennsylvania medical professor Richard Dunbar at a scientific meeting of American Heart Association in New Orleans.

Triglycerides are a type of lipid, or natural oil, usually stored in the body’s fat cells to help provide energy, but when the intake of calories exceeds the body’s ability to store fat in cells, triglycerides can be released into the blood stream. High levels of triglycerides in the blood contribute to atherosclerosis, the hardening of arteries or thickening of artery walls, that increases the risk of heart disease and stroke, as well as pancreatitis, or inflammation of the pancreas. While different from cholesterol, triglycerides circulate in the blood with the help of lipoproteins, proteins that transport lipids, much like cholesterol.

Regeneron is developing evinacumab as a treatment for homozygous familial hypercholesterolemia, a rare inherited condition where the liver cannot naturally process lipoproteins, leading to abnormally high levels of cholesterol and triglycerides, often resulting in early occurrences of heart disease and stroke.  Evinacumab is an injected therapy designed as an antibody that blocks Angiopoietin-like 3, or Angptl3, a protein limiting the activity of enzymes that break down and metabolize fats in the liver, thus stimulating production of triglycerides and cholesterol.

The clinical trial was an early-stage test of evinacumab’s safety and chemical activity in the body. The study team looked primarily for signs of adverse effects among individuals, but also measured triglyceride and cholesterol levels in the blood. Participants in the trial were randomly assigned to receive 1 of 6 different dosage levels of evinacumab, or a placebo.

At the meeting, Dunbar and colleagues reported the first results of the trial from 41 participants, 32 receiving evinacumab and 9 getting the placebo. Results show sharp drops in triglyceride levels among evinacumab recipients, as high as 64 to 73 percent for those receiving the highest doses, well beyond the reductions seen in current treatments. “Current medications such as fibrates or prescription fish oils effectively lower triglycerides,” says Dunbar in a university statement, “but leave much to be desired, each only lowering levels by 20 to 50 percent.”

Results also show lowered cholesterol levels, with the higher the dose of evinacumab, the greater the reductions. But reductions were reported in both the high-density lipoprotein or HDL cholesterol — considered good cholesterol — as well as low-density lipoprotein, or LDL, cholesterol, the kind that contributes to atherosclerosis and heart disease. Reductions in both kinds of cholesterol are considered consistent with limits on Angptl3 proteins.

Participants receiving evinacumab tolerated the treatments, with only headaches reported as adverse effects among 7 participants. The results, say the researchers, provide enough evidence to move forward validating evinacumab as a treatment for people with high triglyceride levels. “In the short term,” notes Dunbar, “profoundly lowering triglycerides may render hospital admissions less frequent in patients prone to pancreatitis, while long term, lowering triglycerides and associated cholesterol could also help reduce the risk of certain heart disease.”

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