Verve doses first patient in VERVE-101 trial

Verve Therapeutics said on June 2 it dosed the first patient in a clinical trial of VERVE-101, a one-time experimental gene-editing medicine designed to lower LDL cholesterol by switching off the PCSK9 gene in the liver. The company has described the treatment as an in vivo adenine base-editing medicine delivered with lipid nanoparticles that carry messenger RNA for the editor and a guide RNA to the target site. The program is part of Verve’s effort to develop single-course treatments for cardiovascular disease rather than chronic pills or injections. Verve, a Boston-based company that agreed to be acquired by Eli Lilly in 2025, has said its cardiovascular pipeline is built around genes linked to atherosclerotic disease. ### What exactly is VERVE-101 trying to do inside the body? ClinicalTrials.gov says VERVE-101 uses base-editing technology designed to disrupt expression of the PCSK9 gene in the liver and lower circulating PCSK9 and LDL-C in patients with established atherosclerotic cardiovascular disease due to heterozygous familial hypercholesterolemia, or HeFH. The study record describes heart-1 as an open-label, Phase 1b, single-ascending dose trial evaluating safety and pharmacodynamic effects. (managedhealthcareexecutive.com) Managed Healthcare Executive reported that Verve described the approach as rewriting a single genomic letter rather than cutting DNA in the way CRISPR-Cas9 is often explained. The outlet said the treatment uses proprietary lipid nanoparticles to deliver an adenine base-editor mRNA and guide RNA. (clinicaltrials.gov) ### Who is the trial for, and how far along is it? ClinicalTrials.gov lists the official title of heart-1 as a study in patients with heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease and uncontrolled hypercholesterolemia. The registry says the trial enrolled 13 patients and had sites in Auckland and Christchurch, New Zealand, and London. (managedhealthcareexecutive.com) Verve’s website says HeFH is an inherited form of familial hypercholesterolemia that causes lifelong, severely elevated LDL cholesterol. The company says its initial program targeted PCSK9 to lower LDL-C as part of a broader effort to address cardiovascular disease, which it calls the leading cause of death worldwide. ### Why does this program draw attention beyond cholesterol treatment? (clinicaltrials.gov) Verve presented VERVE-101 as one of the earliest efforts to use in vivo base editing for cardiovascular disease, and earlier coverage of the heart-1 launch described it as a first human test of base editing for lipid lowering. The focus on PCSK9 matters because the gene is already a validated cholesterol target for marketed medicines, but VERVE-101 aims to change the gene’s activity with a single treatment rather than repeated dosing. (vervetx.com) Eli Lilly said when it announced its planned acquisition of Verve in June 2025 that Verve’s leading programs sought lifelong cardiovascular risk reduction with a single dose. Lilly identified VERVE-102, not VERVE-101, as Verve’s lead program at that point, reflecting how Verve’s newer PCSK9 candidate had moved to the front of the pipeline. (pharmaphorum.com) ### Where does VERVE-101 now sit in Verve’s broader pipeline? Verve’s website currently highlights Heart-2, a trial of VERVE-102, as the company’s enrolling PCSK9 study. The company says Heart-2 is enrolling patients with HeFH or premature coronary artery disease. ClinicalTrials.gov shows heart-1, the VERVE-101 study, as completed, with a last update posted on May 8, 2025. (prnewswire.com) That registry entry indicates the earlier VERVE-101 program generated the first clinical experience for Verve’s PCSK9 editing strategy, while the company’s current public-facing materials emphasize VERVE-102 as the active next-step program. (vervetx.com) ### What comes next for readers tracking this technology? Verve’s publications page lists VERVE-101 alongside VERVE-102 in prior scientific presentations, while the company’s current trial page points readers to Heart-2 for ongoing enrollment. Lilly said in 2025 that VERVE-102 was in a Phase 1b study and had received Fast Track designation from the U.S. Food and Drug Administration. (clinicaltrials.gov) As of June 3, 2026, the most current public milestone visible on Verve’s website is continued Heart-2 enrollment, while the historical ClinicalTrials.gov record for VERVE-101 remains available under study ID NCT05398029. (vervetx.com 1) (vervetx.com 2)