One-time gene therapy may lower up to 62 pc 'bad' cholesterol, clinical trial results show

A one-time gene therapy, VERVE-102, has shown to lower up to 62% of 'bad' cholesterol in the blood in a Phase 1b clinical trial of 35 adults with high cholesterol.

A one-time gene therapy for treating hypercholesterolaemia could lower up to 62 per cent 'bad' cholesterol in the blood, with reductions sustaining over time, according to results of Phase 1b clinical trial published in The New England Journal of Medicine.

Developed by the US-based pharmaceutical and biotechnology giant Eli Lilly and Company, VERVE-102 is an experimental gene therapy that works by durably turning off the 'PCSK9' gene in the liver and lower blood levels of low-density lipoprotein cholesterol (LDL-C) following a single infusion, it said in a statement.

The interim analysis of the 'Heart-2' trial looked at data from 35 adults with heterozygous familial hypercholesterolaemia (HeFH) or premature coronary artery disease (CAD).

''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,'' the statement reads.

It said, ''In this interim analysis of 35 participants, a single dose of VERVE-102 resulted in dose-dependent mean reductions in PCSK9 ranging from 51 per cent to 88 per cent, at the lowest 0.3 milligrams per kilogram dose to the highest 1.0 milligrams per kilogram dose, respectively.''.

Corresponding mean reductions in LDL-C ranged from nine per cent for a dose of 0.3 milligrams per kilogramme, 44 per cent (0.45 milligrams per kilogramme dose), 51 per cent (0.8 milligrams per kilogramme dose), to 62 per cent (1.0 milligrams per kilogramme dose), the company said.

Riyaz S Patel, cardiologist at Barts Health NHS Trust and professor of cardiology at 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.''.

Patel added that many patients with an elevated LDL-C struggle to achieve sustained control despite ongoing efforts with the medicines available today, putting them at a 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,'' Patel said.

The gene therapy, VERVE-102, was found to be well-tolerated across all dose levels with no treatment-related serious adverse events and no dose-limiting toxicities reported, according to the statement.

Adverse events included low-grade infusion-related reactions and fatigue, it said.

''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,'' Sekar Kathiresan, Lilly senior vice president and co-founder of Verve Therapeutics, said.

Lilly plans to begin enrolling the Phase 2 clinical study of VERVE-102 by the end of this year.