Eli Lilly and Company has announced positive phase 1b Heart-2 study results for VERVE-102, an investigational in vivo base editing medicine designed to durably turn off the PCSK9 gene in the liver and lower blood Low-Density Lipoprotein Cholesterol (LDL-C) following a single infusion. The Heart-2 trial is evaluating VERVE-102 in adults with Heterozygous Familial Hypercholesterolemia (HeFH) or premature Coronary Artery Disease (CAD). These data were presented as a late-breaking oral presentation at the European Atherosclerosis Society (EAS) Congress and simultaneously published in The New England Journal of Medicine.

In the Heart-2 study, a single intravenous infusion of VERVE-102 resulted in meaningful lowering of circulating PCSK9 protein and corresponding reductions in LDL-C across all evaluated dose levels. In this interim analysis of 35 participants, a single dose of VERVE?102 resulted in dose-dependent mean reductions in PCSK9 ranging from 51 percent to 88 percent, at the lowest 0.3 mg/kg dose to the highest 1.0 mg/kg dose, respectively. Corresponding mean reductions in LDL-C were 9 percent (0.3 mg/kg), 44 percent (0.45 mg/kg), 45 percent (0.6 mg/kg), 33 percent (0.7 mg/kg), 51 percent (0.8 mg/kg), and 62 percent (1.0 mg/kg). These reductions were sustained over time, with durability observed for up to 18 months following treatment.

Riyaz S Patel, MD, Cardiologist, Barts Health NHS Trust and Professor of Cardiology, University College London, said, "These early data give us encouraging evidence that in vivo base editing of PCSK9 may offer a novel approach to achieving substantial and durable LDL-C reduction with a one-time treatment. Many patients with elevated LDL-C struggle to achieve sustained control despite ongoing efforts with the medicines available today, putting them at significant risk for cardiovascular events. With Coronary Artery Disease still one of the leading causes of death worldwide, the need for new approaches is real."

VERVE?102 was well tolerated across all dose levels with no treatment?related serious Adverse Events (AEs) and no dose?limiting toxicities reported. AEs related to VERVE-102 included low-grade infusion-related reactions and fatigue. All participants received the full planned dose, and no participant withdrew from the study.

Sekar Kathiresan, MD, Senior Vice President, Lilly, and Co-Founder, Verve Therapeutics, said, "Twenty years ago, genetics showed us that people born with PCSK9 naturally turned off have low LDL-C for life and are remarkably protected from heart attack, yet today's chronic therapies struggle to deliver this lifelong lowering. The Heart-2 results provide early clinical evidence that a single dose of VERVE-102 may mimic the LDL-C lowering effects of PCSK9 cardioprotective variants, potentially transforming cardiovascular care from chronic management to a one-time treatment."

The US Food and Drug Administration (FDA) has granted Fast Track designation for VERVE-102 to reduce LDL-C in participants with hyperlipidemia and high lifetime cardiovascular risk. HeFH affects approximately 1 in 200 to 250 people and is characterised by lifelong elevations in LDL-C, leading to premature cardiovascular disease, including CAD. Worldwide, CAD remains a leading cause of death, affecting more than 300 million people.

Lilly plans to initiate the phase 2 clinical study of VERVE-102 by the end of this year.