Eli Lilly posts first data from Verve acquired in vivo base editor in hypercholesterolemia trial

Eli Lilly (NYSE: LLY) [reported](https://www.prnewswire.com/news-releases/a-single-dose-of-lillys-pcsk9-base-editor-verve-102-reduced-pcsk9-by-up-to-88-and-ldl-c-by-up-to-62-with-durable-effects-supporting-its-potential-as-a-one-time-treatment-for-hypercholesterolemia-302780172.html) Phase Ib data from the Heart-2 trial showing that a single infusion of [VERVE-102](https://app.allsci.com/drugs/ASC-DR-0000000043835-1.0-1775585065), an in vivo PCSK9 base editor, reduced LDL cholesterol by up to 62% and PCSK9 protein by up to 88% in adults with heterozygous familial hypercholesterolemia or premature coronary artery disease, with reductions sustained for up to 18 months. The data represent one of the first major clinical updates since Lilly's acquisition of Verve Therapeutics, a deal that expanded Lilly's cardiovascular pipeline into one-time genomic medicines targeting lipid disorders. The [Heart-2 study](https://app.allsci.com/clinical-trial/ASC-CT-0000000001051-1.0-1745615182) is an open-label, single-ascending dose Phase Ib trial enrolling adults with HeFH or premature CAD who require additional LDL-C lowering despite maximally tolerated oral lipid-lowering therapy. This interim analysis covered 35 participants who received a single intravenous infusion of VERVE-102 across six dose cohorts ranging from 0.3 mg/kg to 1.0 mg/kg, with a data cut-off of February 27, 2026 and a median follow-up of approximately nine months; 15 participants had been followed for at least one year. Mean PCSK9 reductions were dose-dependent, ranging from 51% at the lowest dose to 88% at 1.0 mg/kg. Corresponding mean LDL-C reductions ranged from 9% at 0.3 mg/kg to 62% at 1.0 mg/kg, with the 0.8 mg/kg cohort achieving 51% reduction. Both PCSK9 and LDL-C reductions were sustained across the follow-up period of up to 18 months. VERVE-102 was well tolerated across all dose levels, with no treatment-related serious adverse events and no dose-limiting toxicities; reported adverse events were limited to low-grade infusion-related reactions and fatigue. All 35 participants received their full planned dose and none withdrew. The data were presented as a late-breaking oral presentation at the European Atherosclerosis Society Congress and simultaneously published in the New England Journal of Medicine. VERVE-102 uses an adenine base editor delivered via a GalNAc-lipid nanoparticle to introduce a permanent loss-of-function edit in the hepatic PCSK9 gene, mimicking naturally occurring PCSK9 variants associated with lower lifetime cardiovascular risk. The primary differentiator from approved therapies is dosing frequency: Alnylam's Leqvio (inclisiran), an approved siRNA targeting PCSK9 mRNA, requires twice-yearly subcutaneous injections and achieved approximately 50% LDL-C reduction in the ORION Phase III program, while Regeneron's Praluent (alirocumab) and Amgen's Repatha (evolocumab), both PCSK9 monoclonal antibodies, require biweekly or monthly dosing. Cross-trial comparisons are limited by differences in population, background therapy, and study design, and Heart-2 remains an early-phase, uncontrolled, open-label study. Lilly has received FDA Fast Track designation for VERVE-102 and plans to initiate a Phase II study by the end of 2026. *** This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: [https://allsci.com/news/](https://allsci.com/news/) --- Spot something wrong? [Report an issue with this article](https://newsgen-prod.reframedata.com/feedback/verve-102-ldl-cholesterol-eli-lillys-base-editor)