A first-in-human single ascending dose study of a monoclonal antibody against the ANGPTL3/8 complex in subjects with mixed hyperlipidemia
Open Lecture: January & February 2023
A first-in-human single ascending dose study of a monoclonal antibody against the ANGPTL3/8 complex in subjects with mixed hyperlipidemia. Dr. Daniel Gaudet
90th EAS Congress 2022
This lecture was given by Dr. Daniel Gaudet, MD, PhD at the 90th EAS Congress in Milan Italy, 2022.
Dr. Gaudet is the founder and director of the ECOGENE-21 Clinical Research Center in the Department of Medicine, University of Montreal, Canada.
In his excellent lecture, Professor Gaudet presented new data on the effect of a human monoclonal antibody against the angiopoietin-like 3/8 (ANGPTL3/8) complex in subjects with mixed hyperlipidemia.
He started his lecture discussing the role of ANGPTL3/8 in the lipoprotein lipase (LPL) – Triglyceride (TG)-rich lipoproteins machinery and presented data on the effect of loss-of-function (LOF) mutations and pharmacological inhibition of ANGPTL3 on TG, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels.
Subsequently, he presented the design and results of a randomized, double-blind, placebo-controlled study involving 48 subjects with mixed hyperlipidemia (TG levels ≥1.5mmol/L [≥135mg/dL] and LDL-C ≥1.8mmol/L [≥70mg/dL]) who received a single ascending dose of a monoclonal antibody against the ANGPTL3/8 complex, LY3475766 for 28 days,.
He showed that a single dose of LY3475766 significantly reduced TG and remnant cholesterol levels as well as LDL-C, non-HDL-C and apolipoprotein B levels and increased HDL-C levels. There were no serious adverse events. He concluded that inhibition of ANGPTL3/8 complex with LY3475766 may have the potential to reduce cardiovascular risk in these patients when administered on top of optimal standard of care treatment.