A novel type of therapy, known as ANGPTL3 inhibitor therapy, was effective in lowering triglycerides in certain types of patients with severe hypertriglyceridemia (sHTG) who had a prior episode(s) of acute pancreatitis. sHTG is a well-established risk factor for recurrent episodes of acute pancreatitis. These high-risk patients were the focus of a phase 2 study that was led by the Icahn School of Medicine at Mount Sinai and sponsored and funded by Regeneron.
This ANGPTL3 inhibitor therapy, the intravenous drug evicanumab-dgnb, inhibits two important regulators of lipoprotein metabolism. The research, published March 6, in Nature Medicine, found that evinacumab reduced triglycerides by as much as 70 percent in people with sHTG who had at least some lipoprotein lipase (LPL) activity, the key enzyme in triglyceride metabolism. However, in one of the three groups of sHTG patients with genetic mutations resulting in no LPL activity—a rare condition known as familial chylomicronemia syndrome—evinacumab was ineffective in lowering triglycerides. In the other groups, the triglycerides were reduced by a median of 65 to 82 percent. Although the primary endpoint of a reduction in triglycerides did not meet the prespecified significance level, many other triglyceride endpoints were positive.