A single CTX310 infusion inactivated the ANGPTL3 gene in the liver: after one year, LDL cholesterol and triglycerides were lower in four participants who received the highest dose
A single CTX310 infusion inactivated the ANGPTL3 gene in the liver: after one year, LDL cholesterol and triglycerides were lower in four participants who received the highest dose
On August 28, 12-month data from the phase 1 trial of CTX310 were presented at the European Society of Cardiology Congress. A single dose delivers components of the CRISPR-Cas9 system to the liver. The system cuts DNA to inactivate ANGPTL3. Among the four participants who received 0,8 mg/kg, LDL cholesterol at one year was an average of 52,5% below baseline, while triglycerides were 47,8% below baseline.
Lipid-lowering drugs are usually taken for years. CTX310 tests a different way to alter lipid metabolism. A lipid nanoparticle, which is a particle made of fats, delivers messenger RNA encoding Cas9 and a guide RNA targeting the relevant gene to liver cells. Inside these cells, Cas9 and the guide RNA locate ANGPTL3 and cut the DNA. When the cell repairs the break, the gene loses its function in the edited cells.
ANGPTL3 encodes a protein that inhibits enzymes involved in processing fats in the blood. Researchers selected this target based on observations of people with naturally occurring ANGPTL3 variants that prevent the gene from functioning. These variants are associated with a lower risk of cardiovascular disease.
The phase 1 trial enrolled 15 adults with severe lipid disorders that persisted despite maximally tolerated therapy. Five small groups received different doses of a single infusion. Four participants received the highest dose studied, 0,8 mg/kg. The European Society of Cardiology slides report the mean changes in this group after 12 months. LDL cholesterol, meaning cholesterol carried in low-density lipoprotein particles, decreased by 52,5%, while triglycerides, one type of fat found in the blood, decreased by 47,8%.
The trial registry lists safety and tolerability as the primary objective of the phase 1 trial, with changes in ANGPTL3 and lipid levels as secondary measures. The measurements at one year show how long the changes in these markers persisted after a single infusion.