CRISPR Therapeutics reports a 63% triglyceride reduction with CTX310 in Phase 1b, alongside 65% ANGPTL3 reduction in severe hypertriglyceridemia.
Written By: Creola Gonsalves, MS, Biotech
Reviewed By: Pharmacally Editorial Team
CRISPR Therapeutics has reported positive Phase 1b clinical findings for CTX310, an investigational in vivo CRISPR/Cas9 gene-editing therapy targeting angiopoietin-like protein 3 (ANGPTL3), in patients with severe hypertriglyceridemia (sHTG). Presented during a late-breaking oral session at the American Heart Association (AHA) Scientific Sessions 2026, the results showed a mean 63% reduction in triglycerides (TG) and a 65% reduction in circulating ANGPTL3 at Day 30 following a single-course treatment.
The findings are particularly relevant because participants had a median baseline triglyceride concentration exceeding 1,000 mg/dL, indicating substantial lipid abnormalities in the study population. The results provide early clinical evidence that targeting ANGPTL3 through in vivo gene editing can produce substantial triglyceride reductions in patients with severe hypertriglyceridemia.
Phase 1b Trial Design and Patient Characteristics
The multicenter, open-label Phase 1b study evaluated CTX310 in participants with sHTG and fasting serum triglyceride levels above 500 mg/dL. Participants received a single intravenous infusion at a fixed dose of 40 mg for those weighing less than 85 kg or 50 mg for those weighing 85 kg or more. This dosing strategy was designed to approximate the 0.8 mg/kg dose evaluated in Phase 1a. The cohort also included one participant from Phase 1a who received a 56.5 mg dose.
All participants had diabetes, three (30%) had a history of pancreatitis, and two (20%) had clinical atherosclerotic cardiovascular disease (ASCVD).
The study is evaluating safety and tolerability, including dose-limiting toxicities, alongside changes in ANGPTL3, triglycerides, and other lipid parameters, including non-high-density lipoprotein cholesterol (non-HDL-C). Clinical sites are located in New Zealand, Australia, the United Kingdom, and the United States.
Lipid Reductions Extend Beyond Triglycerides
At Day 30, CTX310 demonstrated reductions across several key lipid parameters:
- ANGPTL3: Mean reduction of 65% from baseline
- Triglycerides: Mean reduction of 63%
- Non-HDL-C: Mean reduction of 51%
- Apolipoprotein B (ApoB): Mean reduction of 23%
- LDL-C: Mean reduction of 16% (from a low mean baseline of 60 mg/dL)
The reductions in non-HDL-C and ApoB are particularly relevant because these parameters reflect cholesterol and atherogenic lipoprotein burden beyond triglyceride concentrations alone. However, the LDL-C reduction was comparatively modest, and its interpretation should account for the relatively low baseline level.
The findings suggest that ANGPTL3 editing may influence multiple components of lipid metabolism rather than producing an isolated triglyceride-lowering effect. All 10 participants had at least 30 days of follow-up, while reductions in ANGPTL3 and triglycerides were maintained in participants followed for at least 90 days.
Safety Profile and Early Durability
As of the data cutoff, seven participants had completed at least 90 days of follow-up. CRISPR Therapeutics reported no serious adverse events related to CTX310 and no clinically relevant elevations in aspartate aminotransferase (AST) or alanine aminotransferase (ALT).
One participant experienced a Grade 2 infusion-related reaction, which resolved without preventing completion of the infusion. No Grade 3 or higher adverse events related to CTX310 were reported.
No acute pancreatitis events occurred during the reported study period, despite 30% of participants having a previous history of pancreatitis. However, the small cohort and limited follow-up do not establish whether CTX310 can reduce pancreatitis risk.
The Phase 1b findings also build on previously reported Phase 1a results presented at the European Society of Cardiology (ESC) Congress 2026 and published in The New England Journal of Medicine. In that separate dataset, a single-course treatment demonstrated sustained lipid-lowering effects through one year. At the highest dose, mean reductions were 79% in ANGPTL3, 48% in triglycerides, and 53% in LDL-C. These findings provide preliminary evidence of durability, although the Phase 1a and Phase 1b results represent different clinical populations and datasets.
FDA Grants RMAT Designations
The U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designations to CTX310 for severe hypertriglyceridemia and elevated LDL-C.
The designations provide opportunities for enhanced regulatory interaction and development support, including potential eligibility for accelerated approval and priority review. They do not constitute marketing approval or establish clinical efficacy. CRISPR Therapeutics continues to advance CTX310 in Phase 1b, with additional cohorts evaluating its potential across lipid disorders.
Broader In Vivo Gene-Editing Pipeline
The company is also advancing other liver-directed gene-editing candidates using its lipid nanoparticle (LNP) delivery platform:
- CTX340: Targeting angiotensinogen (AGT) for refractory hypertension
- CTX321: Targeting lipoprotein(a) [Lp(a)] for elevated Lp(a) levels
- CTX460: Targeting SERPINA1 for alpha-1 antitrypsin deficiency using proprietary SyNTase editing technology
The CTX310 findings represent an important early clinical step for in vivo gene editing in lipid disorders. The magnitude of triglyceride and ANGPTL3 reductions following a single infusion supports further clinical investigation. Nevertheless, larger studies and longer follow-up will be necessary to establish the durability, long-term safety, and potential clinical benefits of this approach.
Reference
CRISPR Therapeutics Presents Phase 1b Data for CTX310® Demonstrating Reductions in ANGPTL3 and Triglycerides in Patients with Severe Hypertriglyceridemia at the American Heart Association (AHA) Scientific Sessions 2026, CRISPR Therapeutics, 09 November 2026
A Safety and Tolerability Trial Evaluating CTX310 in Participants with Refractory Dyslipidemias, ClinicalTrials.gov ID NCT07491172
About the Writer
Creola Gonsalves (Linkedin) is an M.S. Biotechnology postgraduate with a strong interest in clinical research, evidence interpretation, and healthcare writing, with a focus on translating life-science knowledge into meaningful real-world insights.
She is trained in Good Clinical Practice (GCP), clinical research principles, and critical interpretation of randomized clinical trials, with certifications from NIH and Stanford University.
Her research background in biotechnological applications and microbial research strengthens her ability to understand scientific evidence and develop clear, accurate, and research-driven healthcare content.