Key Takeaways:
CRISPR Therapeutics' CTX310 cut LDL by a mean 53% and triglycerides 48% one year after a single infusion, Phase 1a data showed.
"A single infusion producing durable reductions at one-year is an encouraging signal that a one-time approach could help close that adherence gap," Luke Laffin, principal investigator and Medical Director of the Cleveland Clinic Coordinating Center for Clinical Research, said.
The open-label, dose-escalation trial enrolled 15 participants across five dose levels from 0.1 to 0.8 mg/kg, all completing at least one year of follow-up. At the highest dose, mean reductions from baseline reached 79% (maximum 89%) for ANGPTL3, 48% (maximum 78%) for triglycerides, and 53% (maximum 84%) for LDL. The findings were published simultaneously in The New England Journal of Medicine.
The durability data support CRISPR Therapeutics' push into in vivo gene editing for cardiometabolic disease, a market where daily lipid-lowering drugs require lifelong adherence. The company is advancing CTX310 in a Phase 1b trial at a flat 0.8 mg/kg dose and expects to share an update focused on severe hypertriglyceridemia in the second half of 2026.
CTX310 was generally well tolerated, with no dose-limiting toxicities or treatment-related serious adverse events and no Grade 3 or higher changes in liver transaminases. One participant experienced an allergic reaction that resolved the following day, and infusion-related reactions occurred in three participants, all Grade 2 and resolved. No new treatment-related safety events emerged during extended follow-up.
The trial enrolled patients with homozygous familial hypercholesterolemia, severe hypertriglyceridemia, heterozygous familial hypercholesterolemia, or mixed dyslipidemias, with uncontrolled triglycerides above 150 mg/dL and/or LDL above 100 mg/dL (or 70 mg/dL for those with established atherosclerotic cardiovascular disease). Most participants were on statins and/or ezetimibe, while 40 percent were taking PCSK9 inhibitors.
"Evidence that a single dose can produce lasting lipid lowering is central to our goal of developing one-time treatments for cardiometabolic diseases," Naimish Patel, chief medical officer at CRISPR Therapeutics, said. CTX310 is one of three cardiovascular programs in the company's in vivo portfolio, alongside CTX340 targeting angiotensinogen for refractory hypertension and CTX321 targeting elevated lipoprotein(a). CRISPR Therapeutics competes with Intellia Therapeutics and Editas Medicine in in vivo gene editing; Editas' EDIT-401, which upregulates the LDL receptor gene, is progressing toward a Phase 1/2 study for heterozygous familial hypercholesterolemia.
The one-year durability data strengthen the case that a single infusion could replace lifelong lipid-lowering therapy, a potential advantage over daily statins and PCSK9 inhibitors that require sustained adherence. Investors will watch the Phase 1b update in the second half of 2026 for confirmation in a larger severe hypertriglyceridemia cohort.
This article is for informational purposes only and does not constitute investment advice.
