CRISPR Therapeutics has reported reductions in triglycerides and LDL cholesterol of more than 80% after a single dose of its in vivo liver editing prospect CTX310, encouraging the company to forge ahead with dose escalation.
CTX310 targets ANGPTL3, a gene that encodes for a protein involved in the regulation of LDL cholesterol. Drug developers are coming at the target from a variety of angles. Regeneron’s antibody Evkeeza hits ANGPTL3, as do siRNA therapies in development at Arrowhead Pharmaceuticals/Eli Lilly. CRISPR Tx and Verve Therapeutics are leading efforts to knock out hepatic ANGPTL3 expression through in vivo editing.
CRISPR Tx shared data on the first 10 recipients of its ANGPTL3 candidate CTX310 as part of its financial results for the first quarter. The study enrolled patients across four diseases associated with elevated levels of LDL or triglycerides.
Based on ANGPTL3 knockdown, CRISPR Tx concluded the two lowest doses were minimally active. In the three patients who received the third dose, CRISPR Tx reported mean reductions in triglycerides and LDL of 55.7% and 28.5%, respectively, 30 days after treatment. LDL fell by 81% after 90 days in one patient on the third dose. Triglycerides and LDL fell 81.9% and 64.6%, respectively, in the one patient in cohort four.
The biotech hailed the results as a significant milestone for the lipid nanoparticle delivery technologies it has developed to get gene editing machinery to targets in the liver. CRISPR Tx is yet to show CTX310 can reduce the risk of cardiovascular events or death, but triglycerides and LDL are established surrogate endpoints that are accepted by regulatory agencies.
CRISPR Tx said no treatment-related severe adverse events or grade three or worse adverse events were reported. No patients had clinically significant changes in liver enzymes, bilirubin or platelets, and there were no dose-dependent trends in the laboratory measurements. Dose escalation is ongoing.