CRISPR Therapeutics' CTX310 shows durable lipid cuts at one year
CRISPR Therapeutics has presented one-year durability data from the Phase 1a trial of CTX310, its investigational in vivo CRISPR/Cas9 gene editing therapy targeting ANGPTL3, at the European Society of Cardiology Congress 2026 in a late-breaking session. The findings were simultaneously published in The New England Journal of Medicine under the title "Durability of CRISPR-Cas9 Gene Editing Targeting ANGPTL3 with CTX310."
The trial enrolled 15 participants across four patient groups: homozygous familial hypercholesterolaemia, heterozygous familial hypercholesterolaemia, severe hypertriglyceridaemia, and mixed dyslipidemias. All participants had completed at least one year of follow-up as of the data cutoff. At the highest dose of 0.8 mg/kg, CTX310 produced mean reductions from baseline of 79% in circulating ANGPTL3 protein, 48% in triglycerides, and 53% in LDL cholesterol. Maximum individual reductions reached 89%, 78%, and 84%, respectively. These effects were dose-dependent and sustained through 12 months of follow-up from a single intravenous infusion.
Safety and tolerability
CTX310 was reported to be well tolerated across all dose cohorts. No dose-limiting toxicities or treatment-related serious adverse events were observed. Infusion-related reactions occurred in three participants at higher doses and were all Grade 2; all resolved and all participants completed their infusions. One allergic reaction, previously reported in the 2025 NEJM publication of initial Phase 1 results, resolved the following day with supportive care. No new liver transaminase elevations or treatment-related adverse events emerged during the extended follow-up period.
Naimish Patel, Chief Medical Officer at CRISPR Therapeutics, said the durability data represent "an important next step for the CTX310 program and for the field of in vivo gene editing," adding that evidence of lasting lipid lowering from a single dose is central to the company's goal of developing one-time treatments for cardiometabolic diseases.
Market context and competitive landscape
The therapeutic case for durable, single-dose lipid lowering is compelling for a clinical reason that the trial's principal investigator, Luke Laffin of the Cleveland Clinic, articulated directly: the primary challenge in managing high cardiovascular risk is not initiating therapy but sustaining it across years or decades of daily dosing. CTX310's one-time delivery model, if confirmed in later-stage trials, would position it against PCSK9 inhibitors currently dominating the refractory hypercholesterolaemia market, including monoclonal antibodies such as evolocumab and alirocumab, as well as the RNA interference agent inclisiran, which requires twice-yearly injections. Notably, 40% of Phase 1a participants were already receiving PCSK9 inhibitors at baseline, suggesting CTX310 was active on top of existing standard of care.
CRISPR Therapeutics is advancing CTX310 into a Phase 1b trial, which is evaluating a fixed flat dose equivalent to the 0.8 mg/kg level used in Phase 1a. The company expects to share initial Phase 1b data from a severe hypertriglyceridaemia cohort in the second half of 2026. Beyond CTX310, the company's in vivo cardiovascular portfolio includes CTX340, targeting angiotensinogen for refractory hypertension, and CTX321, targeting lipoprotein(a). The breadth of this cardiovascular pipeline, all delivered via the company's proprietary lipid nanoparticle platform, suggests CRISPR Therapeutics is building a franchise position in gene-edited cardiometabolic medicine rather than a single-asset programme.
The one-year durability readout, backed by peer-reviewed NEJM publication and presented at the ESC's most prominent podium, provides a credible scientific foundation for the Phase 1b expansion. Investors will nonetheless be watching for Phase 1b cohort data, any sign of late-emerging safety signals at the fixed dose, and the regulatory agency interactions that will shape a potential pivotal trial design.