This study will evaluate pharmacokinetic (PK) and pharmacodynamic (PD) markers for MAT9001 and Vascepa in a 28-day crossover study in patients with elevated triglycerides (150 - 499 mg/dL), building on an earlier study showing that, compared to Vascepa, MAT9001 provided significantly greater reductions in PD markers known to be associated with increased risk of cardiovascular disease, including triglycerides, Total cholesterol, VLDL-C, non-HDL-C, ApoC3
, and PCSK9, without any meaningful increase in LDL cholesterol.
ARO-APOC3 is a subcutaneously administered RNAi therapeutic targeting apolipoprotein C-III (APOC3
) currently being developed as a potential treatment for patients with severe hypertriglyceridemia and FCS.
The new preclinical data presented on ARO-APOC3 and ARO-ANG3 included the following:: A single 2 mg/kg dose of ARO-APOC3 in ApoC3
transgenic mice led to the following observations: Serum ApoC3
levels were reduced by approximately 90%, maximum knockdown was sustained for over three weeks.
Chromosonal SNP array, urine metabolic studies, copper studies, cholesterol studies, 7/8 dehydrocholesterol, creatine kinase, transferrin isoforms, APOC3
, and very long chain fatty acids were found to be normal.
Expressions of APOC3
(GeneID 345) and APOA5 (GeneID) were upregulated by E2.
Rotterdam-based biotech Argenx (EBR: ARGX) reported on Wednesday that preclinical data has been published in Nature Medicine on ARGX-116 inhibiting ApoC3
, a metabolic target correlated with blood lipid levels.
Many later genetic studies have confirmed these findings, including one of our own demonstrating that APOC3
(apolipoprotein C3) loss-of-function heterozygosity led to lifelong low triglycerides and consequently reduced ischemic cardiovascular disease (2, 6).
La RI hepatica tambien aumentaria la produccion y secrecion de VLDL por aumento de la disponibilidad de apolipoproteina B (apo B) y sintesis de ApoC3
y aumentando la expresion de la proteina de transferencia triglicerido microsomal (MTP).
Hypercholesterolemia is associated with the apolipoprotein C-III (APOC3
) genotype in children receiving HAART: an eight-year retrospective study.
Tybjraeg-Hansen, "Loss-of-function mutations in APOC3
and risk of ischemic vascular disease," New England Journal of Medicine, vol.
A proximal part of Chr 9 is known to have many genes relevant to lipid metabolism, including Apoa1, Apoc3
, Apoa4, Apoa5, and Lipc, and multiple QTL including Cq4, Cq5, and Hdlq17  have been reported.
Caption: Figure 2: Plasma ApoC3
significantly decreased in a dose dependent manner in low OxLA (P < 0.05) compared to plain group.