Highlights from

ACC 2021

American College of Cardiology Annual Congress 2021

Virtual 15-17 May 2021

Evinacumab lowers triglyceride levels in severe hypertriglyceridaemia

Summary: Evinacumab resulted in a dramatic reduction in fasting triglyceride levels compared with placebo, but treatment response varied by genotype in a small, phase 2 study.1 Severe hypertriglyceridaemia (ie fasting triglyceride level of ≥500 mg/dL) is a known risk factor for acute pancreatitis.

Angiopoietin-like protein 3 (ANGPTL3) helps to regulate plasma lipid levels via the inhibition of lipoprotein lipase (LPL) and endothelial lipase-mediated hydrolysis of triglycerides and phospholipids.2 A loss of function (LOF) variant on the ANGPTL3 gene results in lower levels of blood triglycerides. Evinacumab is a fully human monoclonal antibody inhibitor of ANGPTL3. A phase II, randomised, placebo-controlled trial (NCT03452228) explored the feasibility of evinacumab as a therapeutic option for severe hypertriglyceridaemia. The trial assigned 51 patients to one of three different cohorts; cohort one (n=17) comprised patients with familial chylomicronaemia syndrome (FCS) and LOF mutations of the LPL pathways; cohort two (n=15) contained patients with multifactorial chylomicronaemia syndrome (MCS) in addition to LPL pathway mutations, and cohort three (n=19) consisted of patients with MCS but no known LPL pathway mutations. The treatment protocol consisted of a 12-week double-blind treatment period followed by a 12-week single-blind treatment period.

Prof Robert Rosenson (Icahn School of Medicine, US) presented the results from the double-blind treatment period at the ACC 2021 Scientific Session. The primary endpoint was change in serum triglyceride (TG) levels at week 12 among participants in cohort three. In this cohort at week 12, the least squares mean reduction in TG was -27.1% (37.4%); 95% CI -71.2 to 84.6, and the corresponding median reduction in TG was -68.8% (95% CI -84.1 to -38.8); an absolute median change in TG of -905 mg/dL. Prof Rosenson noted that response varied across genotypes, and that further investigation is warranted to better understand these differences. A phase IIb trial will be done to assess evinacumab’s ability to prevent acute pancreatitis.

  1. Rosenson RS. A phase 2 trial of the efficacy and safety of evinacumab in patients with severe hypertriglyceridemia. Abstract 406-19, ACC 2021 Scientific Session, 15-17 May 2021
  2. Tikka A, Jauhiainen M. The role of ANGPTL3 in controlling lipoprotein metabolism. Endocrine 2016;52:187-193 [full text]

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