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FDA Lifts Clinical Hold on Verve Therapeutics' VERVE-101 for HeFH

• The FDA has cleared Verve Therapeutics' Investigational New Drug (IND) application for VERVE-101, allowing clinical trials in the U.S. to proceed. • VERVE-101 is a single-course, in vivo base editing medicine targeting the PCSK9 gene to durably lower LDL-C levels in patients. • The heart-1 Phase 1b clinical trial, evaluating VERVE-101 in HeFH patients, is ongoing in the UK and New Zealand, with interim data expected at AHA 2023. • This clearance marks the first clinical development of an in vivo base editing product candidate in the United States.

The U.S. Food and Drug Administration (FDA) has lifted the clinical hold and cleared Verve Therapeutics' Investigational New Drug (IND) application for VERVE-101, enabling the initiation of clinical trials in the United States. This decision paves the way for evaluating VERVE-101 as a treatment for heterozygous familial hypercholesterolemia (HeFH). VERVE-101 is designed as a single-course treatment to inactivate the PCSK9 gene in the liver, aiming for durable reduction of low-density lipoprotein cholesterol (LDL-C) levels.

VERVE-101: A Novel Approach to Lowering LDL-C

VERVE-101 is an investigational in vivo base editing medicine. It targets the PCSK9 gene, which, when inactivated, up-regulates LDL receptor expression, leading to lower LDL-C levels and potentially reducing the risk of atherosclerotic cardiovascular disease (ASCVD). The therapy consists of an adenine base editor messenger RNA and an optimized guide RNA, packaged in a lipid nanoparticle, designed to make a single A-to-G change in the DNA sequence of PCSK9.

heart-1 Clinical Trial Details

The ongoing heart-1 Phase 1b clinical trial is an open-label study in patients with HeFH and established ASCVD. It assesses the safety and tolerability of VERVE-101, along with pharmacokinetic and pharmacodynamic effects, specifically reductions in blood PCSK9 protein and LDL-C levels. The trial is currently being conducted in the United Kingdom and New Zealand. Interim clinical data from the dose-escalation portion of the heart-1 trial, including safety parameters and changes in blood PCSK9 protein and LDL-C levels, are expected to be presented at the American Heart Association's Scientific Sessions 2023.

Clinical Significance and Future Directions

"The clearance of our IND application by the FDA is a significant milestone in our effort to offer patients living with HeFH a transformative alternative to the chronic care model of disease management," said Andrew Bellinger, M.D., Ph.D., chief scientific officer of Verve. "This clearance, for the first time, enables clinical development of an in vivo base editing product candidate in the United States."
Verve plans to activate U.S. clinical trial sites for the heart-1 clinical trial following the IND clearance. The company also intends to apply learnings from the FDA regulatory process to its broader pipeline.

About Heterozygous Familial Hypercholesterolemia (HeFH)

HeFH is a prevalent, life-threatening inherited disease characterized by lifelong elevations in blood LDL-C and accelerated ASCVD. Current management typically involves chronic therapies, and VERVE-101 represents a potentially transformative single-course alternative.
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Reference News

[1]
Verve Therapeutics Announces Clearance of Investigational New Drug Application by the U.S. FDA for VERVE-101 in Patients with Heterozygous Familial Hypercholesterolemia
finance.yahoo.com · Oct 23, 2023

Verve Therapeutics announced FDA clearance of its IND application for VERVE-101, a gene-editing treatment targeting PCSK...

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