Eli Lilly is preparing for a phase 2 study of its cholesterol-lowering gene editor VERVE-102 after updated early-stage data showed sustained reductions in low-density lipoprotein cholesterol (LDL-C), including a 62% decrease in patients who received the highest tested dose.
Lilly said its one-time base editor VERVE-102, which is meant to permanently turn off the cholesterol-producing PCSK9 gene, reduced cholesterol by 62% in patients treated with a one milligram per kilogram dose. The company said the reduction was maintained for up to 18 months. Cholesterol reductions observed at lower dose levels, which had been reported previously by Verve Therapeutics, also remained sustained.
The findings are based on 35 patients enrolled so far in the phase 1b Heart-2 study, which is focused on people with inherited, genetically controlled high cholesterol or premature coronary artery disease (CAD).
VERVE-102 uses a base editor that changes a single letter of DNA without breaking the DNA double helix. The treatment is packaged inside a lipid nanoparticle designed to target the liver.
Scott Vafai, M.D., chief medical officer at Verve Therapeutics, said dosing in the study remains ongoing but declined to comment on whether higher doses may still be tested. Verve is a wholly owned subsidiary of Eli Lilly.
“We’re really excited to share what we think are really encouraging results, demonstrating the potential for one-time treatment to durably lower LDL cholesterol,” Vafai said.
Vafai said VERVE-102’s cholesterol-lowering effect compares favorably with existing PCSK9 inhibitors such as Repatha, which showed cholesterol reductions ranging from 50% to 60% in pivotal trials.
Myles Minter, Ph.D., a healthcare analyst with William Blair who covered Verve before its acquisition by Lilly, said LDL-C lowering above 50% maintained with a good safety profile is generally viewed as an important benchmark. He said VERVE-102’s 62% reduction at the highest dose exceeded that level.
Vafai said elevated cholesterol can be difficult to manage with currently available medicines because patients often stop treatment. He said therapies such as statins and PCSK9 inhibitors are effective at lowering LDL cholesterol, but their real-world effectiveness is limited by high discontinuation rates, adding that up to half of patients stop taking these treatments after one year.
Verve’s earlier effort to target PCSK9 using a base editor encountered liver toxicity issues. According to Vafai, VERVE-102 has avoided similar problems so far through the use of a different nanoparticle delivery system that includes N-Acetylgalactosamine, or GalNac, a sugar that provides another way for the nanoparticle to enter liver cells. He also said the overall formulation of the lipid nanoparticle was changed and pointed to the safety profile seen to date.
Minter said a remaining question for VERVE-102 and other cardiovascular gene editors is determining which patients they will ultimately serve. He said a one-time genetic edit may make sense for younger patients with heterozygous familial hypercholesterolemia, the condition Verve is targeting in its study, while older patients or those without a history of heart attack or stroke may reach a different decision.
Vafai said Verve is currently focused on patients with heterozygous familial hypercholesterolemia and premature CAD, though he said expanding the patient group in the future may be possible following discussions with regulators and additional clinical development. Lilly expects to begin enrolling a phase 2 study of VERVE-102 by the end of the year.
Eli Lilly Reports Promising VERVE-102 Trial Results
Eli Lilly has announced encouraging early clinical trial results for VERVE-102, an investigational gene-editing therapy designed to lower LDL cholesterol, often referred to as “bad cholesterol.” In the Phase 1b Heart-2 study, participants receiving the highest dose experienced LDL cholesterol reductions of up to 62% following a single intravenous infusion. The therapy also reduced PCSK9 protein levels by as much as 88%, demonstrating its potential as a long-lasting treatment for individuals at high cardiovascular risk.
How Eli Lilly’s VERVE-102 Works
Eli Lilly developed VERVE-102 to target the PCSK9 gene in the liver using advanced base-editing technology. By permanently switching off this gene, the treatment aims to reduce LDL cholesterol production and maintain lower cholesterol levels over time. Unlike traditional cholesterol medications that require ongoing use, VERVE-102 is being evaluated as a one-time treatment with durable effects lasting up to 18 months in early trial participants.
The latest findings position Eli Lilly at the forefront of gene-editing innovation in cardiovascular medicine. If future studies confirm these results, VERVE-102 could offer a groundbreaking approach to managing inherited high cholesterol and reducing the long-term risk of heart disease. The possibility of achieving substantial LDL cholesterol reduction through a single treatment could transform how cardiovascular conditions are treated worldwide.
According to Eli Lilly, VERVE-102 was generally well tolerated across all tested dose levels. Researchers reported no treatment-related serious adverse events or dose-limiting toxicities. The most common side effects were mild infusion-related reactions and fatigue. Based on these positive findings, Eli Lilly plans to begin Phase 2 clinical studies later this year to further evaluate the therapy’s safety and effectiveness.
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