Phase 1/2 trial · N Engl J Med 2025
CTX310 phase 1 trial
Phase 1 Trial of CRISPR-Cas9 Gene Editing Targeting ANGPTL3.
The bottom line
A single dose of the CRISPR-Cas9 gene-editing therapy CTX310 was generally well tolerated and produced dose-dependent reductions in ANGPTL3 levels, supporting further clinical development for dyslipidemia.
Early safety/biomarker dataUS status: Investigational
At a glance
- Medicine
- Single intravenous dose of CTX310 (lipid-nanoparticle-encapsulated CRISPR-Cas9 mRNA and guide RNA targeting hepatic ANGPTL3) at 0.1, 0.3, 0.6, 0.7, or 0.8 mg per kilogram
- Compared with
- None (single-arm, ascending dose)
- People
- 15
- Who took part
- Adults who had uncontrolled hypercholesterolemia, hypertriglyceridemia, or mixed dyslipidemia and were receiving maximally tolerated lipid-lowering therapy
- Design
- ascending-dose phase 1 trial
- Follow-up
- at least 60 days
- Main question
- Adverse events, including dose-limiting toxic effects
Main result
No dose-limiting toxic effects related to CTX310 occurred.
Effect on LDL cholesterol
Not reported in abstract (ANGPTL3 level changes reported instead)
Other results
one participant died suddenly 179 days after treatment with the 0.1-mg-per-kilogram dose
Safety
Serious adverse events occurred in two participants (13%): one participant had a spinal disk herniation, and the other died suddenly 179 days after treatment with the 0.1-mg-per-kilogram dose. Infusion-related reactions were reported in three participants (20%), and one participant (7%) who had elevated levels of aminotransferases at baseline had a transient elevation in aminotransferases to between three times and five times as high as those at baseline, peaking on day 4 and returning to baseline by day 14.
In the trial's own words
“The mean percent change in ANGPTL3 level was 9.6% (range, -21.8 to 71.2) with the dose of 0.1 mg per kilogram, 9.4% (range, -25.0 to 63.9) with 0.3 mg per kilogram, -32.7% (range, -51.4 to -19.4) with 0.6 mg per kilogram, -79.7% (range, -86.8 to -72.5) with 0.7 mg per kilogram, and -73.2% (range, -89.0 to -66.9) with 0.8 mg per kilogram.”
Quoted from the abstract of N Engl J Med 2025, checked word for word against PubMed. PubMed 41211945 · Full paper (DOI)
How this medicine works, where it stands and what it costs: CTX310
Common questions
What did the CTX310 phase 1 trial find?
A single dose of the CRISPR-Cas9 gene-editing therapy CTX310 was generally well tolerated and produced dose-dependent reductions in ANGPTL3 levels, supporting further clinical development for dyslipidemia.
Who was in CTX310 phase 1?
15 people. Adults who had uncontrolled hypercholesterolemia, hypertriglyceridemia, or mixed dyslipidemia and were receiving maximally tolerated lipid-lowering therapy.
What was CTX310 phase 1's main result?
No dose-limiting toxic effects related to CTX310 occurred.
How much did LDL cholesterol change in CTX310 phase 1?
Not reported in abstract (ANGPTL3 level changes reported instead)
Related trials
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- PALISADE (2025)In patients with persistent chylomicronemia, plozasiran (siRNA against APOC3) sharply lowered triglycerides and reduced acute pancreatitis episodes compared with placebo, with a similar overall adverse event rate but a signal for hyperglycemia in those with prediabetes/diabetes.
- PROLONG-ANG3 (2025)In adults with mixed dyslipidaemia on background statin therapy, solbinsiran 400 mg significantly reduced apoB levels compared with placebo and was generally well tolerated, though its effect on cardiovascular outcomes is still unknown.
- ARCHES-2 (2024)In adults with mixed hyperlipidemia, zodasiran (an RNAi therapy against ANGPTL3) produced significant, dose-dependent reductions in triglycerides and improvements in non-HDL-C, ApoB, and LDL-C compared with placebo, with a signal of transient HbA1c elevation in diabetic patients at the highest dose.
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