Verve Starts Human Trials for Gene Editing Medicine, Targeting Heterozygous Familial Hypercholesterolemia

Verve announced its novel gene-editing medicine VERVE-101, which is currently under Phase 1b clinical trial, having its very first patient getting dosed. VERVE-101 is targeting patients with heterozygous familial hypercholesterolemia (HeFH), a prevalent and life-threatening subtype of atherosclerotic cardiovascular disease (ASCVD). As an investigational gene-editing medicine, it was designed to be a single-course treatment that hoped to permanently turn off the PCSK9 gene in the liver to reduce low-density lipoprotein cholesterol (LDL-C), or known as “bad cholesterol”.

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CRISPR Technology in Disease Treatment

VERVE-101 consists of an adenine base editor messenger RNA and an optimized guide RNA targeting the PCSK9 gene packaged in an engineered lipid nanoparticle. It’s designed to change adenine in PCSK9 to guanine. The A-G swap will inactivate the PCSK9 gene, while the inactivation has been shown to up-regulate LDLR expression, which leads to lower LDL-C levels, hence reducing the risk for ASCVD.

The novel drug based on a more precise form of CRISPR known as base editing marked the latest milestone in CRISPR technology for altering human DNA to treat diseases.

The Ongoing Heart-1 Trial

“Preclinical data suggest that VERVE-101 has the potential to offer people with HeFH a game-changing treatment option, transforming the traditional chronic care model to a single-course, life-long treatment solution,” said Sekar Kathiresan, M.D., co-founder, and chief executive officer of Verve.

The current standard of care treatment for HeFH is highly dependent on patient adherence, lifestyles, health care access, and infrastructure, which largely limits the efficacy to achieve LDL-C goal levels. The low success rate of not more than 20% called for an urgent need for better treatment alternatives. VERVE-101 has the potential to break through the bottleneck of current treatment, and the company was optimistic to promote it to the millions of people with ASCVD globally.

The heart-1 clinical trial is planned to enroll approximately 40 adult HeFH patients with established ASCVD and the primary endpoint will focus on the safety and tolerability of VERVE-101 administration, with additional analyses for pharmacokinetics and blood PCSK9 protein and LDL-C reductions. The initial results are expected sometime in 2023, according to Verve.

Author

Nai Ye Yeat