Editas Medicine’s EDIT-401 Cuts LDL-C by ≥90% for Six Months in Primates
Editas Medicine’s preclinical data shows a single 1.5–3.0 mg/kg dose of EDIT-401 in non-human primates produced ≥90% mean LDL-C reduction durable through six months with a promising safety profile and no adverse observations at therapeutically relevant doses. EDIT-401 achieved ≥6-fold hepatic LDLR protein increase with only 10–40% functional editing, while mouse studies indicate dose adjustments may not be needed for heterozygous familial hypercholesterolemia patients.
1. Preclinical Efficacy in Non-Human Primates
A single intravenous dose of EDIT-401 at 1.5–3.0 mg/kg achieved a mean LDL-C reduction of ≥90% across all dose groups in non-human primates, with rapid onset and sustained effect through approximately six months. This level of efficacy was attained with only 10–40% functional editing of LDLR alleles and corresponded to a ≥6-fold increase in hepatic LDLR protein levels.
2. Safety and Targeted Delivery Profile
EDIT-401 demonstrated a favorable preclinical safety profile with no adverse clinical observations at the therapeutically relevant 1.5 mg/kg dose. Tissue distribution studies showed highest delivery to hepatocytes, minimal off-target exposure in non-target tissues, and undetectable delivery to oocytes, supporting a focused hepatic editing approach.
3. Mouse Model Findings and Upregulation Strategy
Pharmacokinetic and pharmacodynamic data in heterozygous Ldlr loss-of-function and wild-type mice indicate that fixed dosing may suffice to lower LDL-C in HeFH patients without adjustment. Additional findings leveraging DNA large language models highlight the broader potential of Editas’ in vivo gene upregulation platform to augment compensatory pathways and accelerate novel gene editing medicines.