Eli Lilly and Company reported positive interim results from the Phase 1b Heart-2 clinical study of VERVE-102, an investigational gene-editing therapy designed to lower low-density lipoprotein cholesterol (LDL-C) with a single infusion, potentially offering a new treatment approach for patients at high risk of cardiovascular disease.
The early-stage study findings, presented during a late-breaking oral session at the European Atherosclerosis Society (EAS) Congress and simultaneously published in The New England Journal of Medicine, demonstrated meaningful and sustained reductions in both circulating PCSK9 protein and LDL cholesterol among patients treated with the experimental medicine.
VERVE-102 is an investigational in vivo base-editing therapy aimed at permanently switching off the PCSK9 gene in the liver. The gene plays a key role in regulating LDL cholesterol, commonly referred to as “bad cholesterol,” which is strongly associated with cardiovascular disease risk. By targeting PCSK9, Lilly aims to provide a durable reduction in cholesterol levels through a one-time treatment rather than chronic medication.
The Heart-2 trial is evaluating VERVE-102 in adults diagnosed with heterozygous familial hypercholesterolemia (HeFH) or premature coronary artery disease (CAD), conditions associated with elevated cholesterol and increased cardiovascular risk.
In an interim analysis involving 35 participants, a single intravenous dose of VERVE-102 produced dose-dependent reductions in PCSK9 protein levels ranging from 51% at the lowest tested dose of 0.3 mg/kg to 88% at the highest dose of 1.0 mg/kg. Corresponding reductions in LDL cholesterol ranged from 9% at the lowest dose to 62% at the highest dose.
Participants receiving intermediate dose levels also experienced notable LDL-C reductions, including 44% at 0.45 mg/kg, 45% at 0.6 mg/kg, 33% at 0.7 mg/kg, and 51% at 0.8 mg/kg. Importantly, researchers reported that cholesterol-lowering effects remained durable, with reductions sustained for as long as 18 months after treatment.
Researchers involved in the study described the findings as encouraging, particularly given the persistent challenge many patients face in maintaining long-term cholesterol control despite currently available therapies.
Riyaz S. Patel, a cardiologist at Barts Health NHS Trust and professor of cardiology at University College London, said the findings suggest that in vivo base editing of PCSK9 may provide a novel method to achieve substantial and lasting reductions in LDL cholesterol using a one-time treatment. He emphasized that many patients with elevated cholesterol remain at risk of cardiovascular events even while receiving conventional therapies.
Safety findings also appeared favorable in the interim analysis. Lilly reported that VERVE-102 was well tolerated across all tested dose levels, with no treatment-related serious adverse events or dose-limiting toxicities observed. Treatment-related side effects included low-grade infusion-related reactions and fatigue. No participant withdrew from the study, and all patients received the planned full dose.
Sekar Kathiresan, Lilly senior vice president and co-founder of Verve Therapeutics, said the results provide early evidence that VERVE-102 could replicate the lifelong cholesterol-lowering benefits seen in individuals naturally born with inactive PCSK9 gene variants, who are known to have reduced risks of heart attacks.
The U.S. Food and Drug Administration has granted Fast Track designation to VERVE-102 for lowering LDL cholesterol in people with hyperlipidemia and elevated lifetime cardiovascular risk.
Heterozygous familial hypercholesterolemia affects an estimated one in every 200 to 250 people globally and significantly increases the likelihood of early cardiovascular disease. Coronary artery disease remains one of the world’s leading causes of death, affecting more than 300 million people worldwide.
Following the positive interim data, Lilly said it plans to begin a Phase 2 clinical trial of VERVE-102 by the end of the year, advancing development of a therapy that could potentially shift cardiovascular treatment from long-term disease management to a one-time intervention.