A phase two global study has confirmed that the investigational drug evinacumab can successfully reduce triglycerides in patients with acute pancreatitis.
The study, led by scientists at Mount Sinai, has indicated that evinacumab – monoclonal antibody medication – can efficiently decrease triglycerides in people suffering from pancreatitis and hypertriglyceridemia (sHTG), diminishing triglyceride levels by up to 82%, reducing the risk of recurrent acute pancreatitis.
Robert S. Rosenson, the lead investigator of the study and Professor of Medicine at the Icahn School of Medicine at Mount Sinai, said: “Evinacumab has the potential to not only lower triglycerides, but the risk of acute pancreatitis, quality of life, and the risk of cardiovascular events in a highly vulnerable patient population.
“The unmet clinical need couldn’t be greater. Even after the current therapeutic options of dietary counselling, fibrates, and omega-3 fatty acid products, many individuals with severe hypertriglyceridemia have elevated triglyceride levels above 500 mg/dL, and some in the thousands.”
Hypertriglyceridemia is an inflammatory pancreatic condition that prompts symptoms of abdominal pain and fever, this potentially life-threatening condition is caused when triglyceride levels surpass 500 mg/dL and are estimated to be responsible for 10% of acute pancreatitis cases. The most common causes of the condition are alcoholism and gallstones, with recurrent acute pancreatitis often requiring hospital care.
To conduct their investigation, the team analysed 52 patients with severe hypertriglyceridemia, discovering that clinical improvements were dependant on genetic variants; patients not demonstrating two mutations in the lipoprotein (LPL) pathway – an enzyme that breaks down triglycerides – showed the most substantial triglyceride reduction, with 82% achieved.
There was a 65% reduction in triglycerides demonstrated in the second group of patients who had a genetic disorder called multifactorial chylomicronemia syndrome (MCS). Finally, in the third group who had a condition known as familial chylomicronemia syndrome (FCS), there was no reduction in triglyceride levels.
Rosenson said: “Our research underscored the importance of genetic testing of the LPL pathway to determine which patients are most likely to respond well to evinacumab therapy. In patients with two LPL mutations who experienced no reduction in triglycerides, there were reductions in non-HDL cholesterol and in the cholesterol content of triglyceride-rich lipoproteins, demonstrating that evinacumab was impacting the triglyceride pathway.”
The function of evanacumab
To achieve these effects, evanacumab attaches to and blocks the function of a protein that is influential in cholesterol metabolism called angiopoietin-like protein 3 (ANGPTL3). People deficient in ANGPTL3 demonstrate substantially low lipid levels as a result of genetic causes, signifying that this could be utilised to lower triglycerides.
The next phase of the clinical trial for evanacumab will be aimed at patients with severe hypertriglyceridemia to evaluate the reduction in the risk of acute pancreatitis. Rosenson said: