CRISPR Therapeutics Reports Promising Results for In Vivo Liver Editing Therapy

CRISPR Therapeutics has announced significant progress in its development of CTX310, an in vivo liver editing therapy targeting the ANGPTL3 gene. The company reported substantial reductions in triglycerides and LDL cholesterol levels following a single dose of the experimental treatment, marking a potential breakthrough in the field of gene editing for cardiovascular disease management.

Impressive Efficacy in Early-Stage Trial

In a recent financial report, CRISPR Therapeutics shared data from the first 10 recipients of CTX310, enrolled across four diseases associated with elevated levels of LDL or triglycerides. The results showed remarkable reductions in key lipid markers:

• In the three patients who received the third dose, mean reductions in triglycerides and LDL of 55.7% and 28.5%, respectively, were observed 30 days after treatment.
• One patient on the third dose experienced an 81% reduction in LDL after 90 days.
• A single patient in cohort four demonstrated even more striking results, with triglycerides and LDL falling by 81.9% and 64.6%, respectively.

These outcomes have encouraged the company to proceed with dose escalation in the ongoing trial.

Safety Profile and Technical Achievements

The preliminary safety data for CTX310 appears promising. CRISPR Therapeutics reported no treatment-related severe adverse events or grade three or worse adverse events. Furthermore, there were no clinically significant changes in liver enzymes, bilirubin, or platelets, and no dose-dependent trends were observed in laboratory measurements.

The company highlighted these results as a significant milestone for their lipid nanoparticle delivery technologies, which are crucial for transporting gene editing machinery to liver targets. While CTX310 has yet to demonstrate a reduction in cardiovascular events or mortality, the substantial decreases in triglycerides and LDL – established surrogate endpoints accepted by regulatory agencies – are encouraging signs for the therapy's potential efficacy.

Competitive Landscape in ANGPTL3-Targeted Therapies

CTX310's target, the ANGPTL3 gene, encodes a protein involved in LDL cholesterol regulation. This approach places CRISPR Therapeutics in competition with other pharmaceutical companies pursuing similar goals through various methods:

• Regeneron's antibody Evkeeza, which directly targets ANGPTL3
• Arrowhead Pharmaceuticals and Eli Lilly's siRNA therapies in development
• Verve Therapeutics' parallel efforts in in vivo editing to knock out hepatic ANGPTL3 expression

As CRISPR Therapeutics advances its clinical program, the race to bring effective ANGPTL3-targeted therapies to market intensifies, potentially offering new options for patients with lipid disorders and associated cardiovascular risks.