Promising early data has been revealed from the first clinical study of a gene editing therapy to lower the risk of heart disease, setting the stage for competition with similar treatments.
The CRISPR Therapeutics therapy, dubbed CTX310, uses lipid nanoparticles (LNPs) to deliver the CRISPR therapy into the liver, where it cuts a gene called ANGPTL3. The approach aims to mimic the effects of natural mutations that cause some people to have unusually low levels of cholesterol and triglycerides.
The phase 1 trial tested four dose levels in 10 people, but the most dramatic results came from the sole patient who got the highest dose, which reduced their triglyceride levels by 82% and low-density lipoprotein (LDL) – often called “bad” cholesterol – by 65% a month after the infusion.
Three patients who got the second-highest dose had their triglycerides reduced by an average of 56% and their LDL cholesterol by an average of 29%, although one of those patients had an 81% reduction. The six people who got the smallest two doses had only minor triglyceride reduction.
The topline results were announced last week, the first time CRISPR Therapeutics has shared results from a study testing its namesake technology as an infusion directly into the body.
“We’re seeing dramatic reductions in triglycerides,” CRISPR Therapeutics CEO Samarth Kulkarni told Endpoints News. “Gene editing works.”
Much larger studies will be needed to prove the safety and efficacy of the drug, but the preliminary results build on positive data from Beam Therapeutics, Intellia Therapeutics and Verve Therapeutics, which have also successfully used lipid nanoparticles to deliver gene editing therapies to the liver.
“Once we establish an LNP platform for the liver, we can keep adding targets and developing more drugs in a de-risked fashion,” Kulkarni said. “And the mRNA we make is applicable to all of the programs, so our costs are going to go down over time, too.”
Lipid-lowering competition
The company hopes that its treatment may one day lower the risk of heart disease in many people. But first, it is testing the drug in patients with severe conditions, including familial hypercholesterolemia, severe hypertriglyceridemia, and mixed dyslipidemias.
It said the two highest doses of its therapy reduced ANGPTL3 by up to 75%, but didn’t say what the average reduction was. There were no severe adverse reactions to the drug. And there were no meaningful changes to liver enzyme levels or platelets, two potential problems caused by some gene therapies.
CRISPR’s triglyceride reduction appears roughly on par with the 52% lowering seen in a phase 2 study of solbinsiran, an siRNA drug made by Eli Lilly that also targets ANGPTL3. But CRISPR Therapeutics is quick to note its potential edge in LDL cholesterol, which Lilly’s drug only reduced by about 12% to 17%.
“The LDL reduction seems to be a lot higher than some of the siRNA therapies. So this could end up being a best-in-class therapy,” Kulkarni said. “So from that perspective, we’re thrilled.”
Regeneron already sells an antibody drug called Evkeeza that also targets ANGPTL3. In a study of people with familial hypercholesterolemia, the drug reduced LDL cholesterol by 49% and triglycerides by 50%.
By targeting a different gene called PCSK9, Verve has reduced LDL cholesterol levels by about 53% in a recent study. The company also began a clinical trial of a therapy that targets ANGPTL3 last year, and it expects to share updates in the second half of 2025.
CRISPR Therapeutics expects to present more details at a medical conference in the second half of 2025. The company is also planning to share data from a phase 1 study of a similar therapy that aims to reduce lipoprotein(a), another lipid linked to heart disease, in the second quarter this year.
Casgevy and CBER
The company also shared an update on the commercial launch of Casgevy, its CRISPR-edited cell therapy for sickle cell disease and beta thalassemia.
More than 90 patients have had their bone marrow stem cells collected to begin the process of making the therapy, and the company expects that number will “grow significantly” this year, the company said.
Kulkarni told Endpoints that eight patients received Casgevy in the first quarter of 2025, a notable uptick from previous quarters but still a far cry from the roughly 300 patients the company needs to treat each year to break even on the therapy, according to one analyst.
See more from MedicalBrief archives:
CRISPR treatment now approved for beta thalassemia
Gene-editing cholesterol trial paves way for groundbreaking treatment
Verve Therapeutics announces lowering of LDL-C with single gene editing treatment