First Patient With Familial Hypercholesteremia Dosed With Base-Editing Therapy


Verve Therapeutics is currently conducting a clinical trial in New Zealand and expects to be able to open trials in the UK and US later in 2022.

Verve Therapeutics’ phase 1b heart-1 clinical trial (NCT05398029) of VERVE-101, a gene-editing medicine, has dosed its first patient with heterozygous familial hypercholesterolemia (HeFH) in New Zealand.1

“VERVE-101 is a first-in-class gene editing medicine that we have designed to make a single spelling change in liver DNA to permanently turn off a disease-causing gene. The dosing of the first human with such an investigational base editing medicine represents a significant achievement by our team and for the field of gene editing,” Sekar Kathiresan, MD, co-founder and chief executive officer, Verve Therapeutics, said in a statement.1 “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.”

The novel, investigational in-vivo base-editing CRISPR therapy VERVE-101 is designed to permanently turn off the PCSK9 gene in the liver to reduce low-density lipoprotein cholesterol (LDL-C) in patients with HeFH, a subtype of atherosclerotic cardiovascular disease (ASCVD). The therapy will be evaluated in the heart-1 trial, which plans to enroll approximately 40 adult patients with HeFH and established ASCVD. The trial will evaluate the safety and tolerability of VERVE-101 administration as well as pharmacokinetics and reductions in blood PCSK9 protein and LDL-C.

READ MORE: Early Momentum for a Genomic Approach to Sickle Cell Disease Therapy

The first part of the trial will assess the therapy in a single, ascending dose arm followed by a second-dose expansion cohort and then an optional second-dose cohort. Verve expects to report interim clinical data from the trial safety parameters, blood PCSK9 level and blood LDL-C level in 2023.

“Our ultimate goal with VERVE-101 is to bring a new option to the millions of people with ASCVD around the world, and dosing participants in the Phase 1 study for this first indication, HeFH, is a key inflection point to achieving that goal,” Andrew Bellinger, MD, PhD, chief scientific and medical officer, Verve Therapeutics, added to the statement.1 “With the current standard of care treatment for HeFH, less than 20% of patients achieve LDL-C goal levels due to the limitations of the chronic model which requires rigorous patient adherence, regular health care access, and extensive health care infrastructure. VERVE-101 has the potential to change the way cardiovascular disease is cared for by lowering LDL-C as low as possible for as long as possible after a single treatment.”

Verve Therapeutics received clearance for the heart-1 clinical trial to be conducted in New Zealand in May 2022.2 The company is currently applying for a clinical trial application in the UK and for investigational new drug (IND) clearance in the US, with updates expected in the second half of 2022.

“The remaining IND-enabling studies are on track to be completed in the third quarter, and we are prepared to rapidly submit our IND upon completion. This is a momentous year as we continue our mission of transforming the treatment of cardiovascular disease from the current chronic care model to that of single-course gene editing medicines,” Kathiresan said in a previous statement.2

1. Verve Therapeutics doses first human with an investigational in vivo base editing medicine, VERVE-101, as a potential treatment for heterozygous familial hypercholesterolemia. News release. Verve Therapeutics. Verve Therapeutics. July 12, 2022.
2. Verve Therapeutics announces clearance of first VERVE-101 clinical trial application and outlines global clinical development strategy; reports first quarter 2022 financial results. News release. Verve Therapeutics. May 10, 2022.
Related Videos
Julie Kanter, MD
Mark Walters, MD
Julie Kanter, MD
© 2023 MJH Life Sciences

All rights reserved.