Eli Lilly reported positive interim Phase 1b Heart-2 results for VERVE-102, an investigational in vivo base editing therapy targeting PCSK9 to lower LDL-C. The single-infusion treatment achieved dose-dependent, durable cholesterol reductions with a favorable safety profile, supporting advancement to Phase 2 in 2026.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
Eli Lilly reported positive interim Phase 1b Heart-2 results for VERVE-102, an investigational gene editing therapy for heterozygous familial hypercholesterolemia (HeFH) and premature coronary artery disease (CAD). In the study, a single infusion reduced low-density lipoprotein cholesterol (LDL-C) by up to 62% and maintained durable LDL-C lowering for up to 18 months, with no treatment-related serious adverse events reported. The data were presented at the European Atherosclerosis Society Congress and published in The New England Journal of Medicine.
Trial Design
Heart-2 (NCT06164730) is an open-label, single-ascending dose Phase 1b study in adults with heterozygous familial hypercholesterolemia (HeFH) or premature coronary artery disease (CAD) requiring additional LDL-C lowering despite maximally tolerated oral therapy. In this interim analysis, 35 participants received a single intravenous infusion of VERVE-102 across six dose cohorts (0.3–1.0 mg/kg). Each infusion lasted about four hours, all participants received the full planned dose, and none withdrew. As of the February 27, 2026 cut-off, median follow-up was nine months, with 15 participants followed for at least one year and some up to 18 months.
Efficacy Findings
A single infusion of VERVE-102 resulted in meaningful, dose-dependent reductions in circulating PCSK9 protein and LDL-C across all evaluated dose levels. Mean PCSK9 reductions ranged from 51% at 0.3 mg/kg to 88% at 1.0 mg/kg. Corresponding mean LDL-C reductions were 9% (0.3 mg/kg), 44% (0.45 mg/kg), 45% (0.6 mg/kg), 33% (0.7 mg/kg), 51% (0.8 mg/kg), and 62% (1.0 mg/kg). These reductions were sustained over time, with durability observed for up to 18 months in some participants.
Safety Findings
VERVE-102 was well tolerated across all dose levels. No treatment-related serious adverse events, dose-limiting toxicities, or study discontinuations were reported. Adverse events consisted primarily of low-grade infusion-related reactions and fatigue. All participants received the full planned dose, underscoring a favorable early safety profile.
Drug Profile
VERVE-102 delivers messenger RNA encoding an adenine base editor and a guide RNA targeting PCSK9 through a proprietary GalNAc-lipid nanoparticle platform. The therapy edits hepatocytes after a single intravenous infusion, suppressing PCSK9 production, enhancing LDL receptor activity, and lowering circulating LDL-C. The approach aims to replicate naturally occurring cardioprotective PCSK9 variants linked to lifelong low LDL-C levels and reduced cardiovascular risk.
Expert Opinions
Commenting on the results, Riyaz S. Patel, M.D., cardiologist at Barts Health NHS Trust and professor of cardiology at University College London, said the data support the potential of one-time PCSK9 editing to deliver substantial and durable LDL-C lowering for patients struggling to maintain long-term lipid control.
Sekar Kathiresan, M.D., Lilly senior vice president and Verve Therapeutics co-founder, added that the findings may validate a strategy that replicates naturally occurring protective PCSK9 variants.
Regulatory Status
The FDA has granted Fast Track designation to VERVE-102 for patients with hyperlipidemia and elevated cardiovascular risk. HeFH affects about 1 in 200–250 people and is linked to premature cardiovascular disease, including CAD. CAD remains a leading global cause of death, affecting more than 300 million people. Lilly expects to begin Phase 2 later in 2026.
Pipeline Context
Verve is also advancing VERVE-201 in the Pulse-1 Phase 1b trial, targeting the ANGPTL3 gene, as part of Lilly’s broader cardiovascular gene editing strategy.
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About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.