Verve Therapeutics’ VERVE-101 Demonstrates Breakthrough in vivo Base Editing for Familial Hypercholesterolemia
15 November 2023
Verve Therapeutics‘ VERVE-101 shows promising reductions in LDL-C and PCSK9 protein in the first human proof-of-concept for in vivo base editing in patients with familial hypercholesterolemia. The data showed that VERVE-101 could meaningfully and durably lower LDL-C in these patients.
Clinical-stage biotechnology company, Verve Therapeutics, has announced interim data for VERVE-101, an investigational, in vivo base editing medicine designed to be a single-course treatment that inactivates the PCSK9 gene in the liver to durably lower blood LDL-C, demonstrating the first human proof-of-concept for in vivo base editing.
In the ongoing open-label heart-1 Phase Ib clinical trial, VERVE-101 is being tested to evaluate the safety and tolerability in patients with the inherited disease heterozygous familial hypercholesterolemia (HeFH), established accelerated atherosclerotic cardiovascular disease (ASCVD), and uncontrolled hypercholesterolemia – aiming to develop a single-course gene editing medicine for cardiovascular disease. The disease is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) in the blood, leading to ASCVD.
“Of the more than three million people with HeFH in the U.S. and Europe, very few are currently at LDL-C goal, due in part to a care model that requires lifetime therapies.” Said Deepak L. Bhatt, M.D., M.P.H., Director of the Mount Sinai Fuster Heart Hospital and the Dr. Valentina Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine in New York.
“I am very encouraged by the initial data from the heart-1 trial that demonstrated the potential for single-course gene editing as a new approach to treat patients with HeFH,” continued Bhatt.
heart-1 Efficacy Analysis: Dose-dependent reductions in LDL-C and blood PCSK9 protein were observed following a single infusion of VERVE-101. Reductions of up to 55% in LDL-C and up to 84% in blood PCSK9 protein suggest potential therapeutic benefits. Blood PCSK9 protein and LDL-C reductions are quantified as percent change from baseline using the time-weighted average from day 28 through last available follow-up.
heart-1 Safety and Tolerability: Safety events were consistent with the severe, advanced ASCVD patient population, and adverse events were well-tolerated.VERVE-101 was well-tolerated in the two lower dose cohorts, with no treatment-related adverse events observed. Treatment-related adverse events were observed, in the two higher dose cohorts, including transient, mild or moderate infusion reactions and transient, asymptomatic increases in liver transaminases with mean bilirubin levels below the upper limit of normal.
All infusion reactions and liver transaminase elevations resolved without clinical sequelae.
Dose-dependent reductions in blood PCSK9 protein levels and LDL-C were observed, with potential therapeutic doses showing meaningful and durable reductions.
Verve plans to initiate a randomized, placebo-controlled Phase II clinical trial of either VERVE-101 or VERVE-102 in 2025. In the current trial, nine patients in the trial had prior coronary revascularizations, and four had prior myocardial infarctions. Currently, the enrollment process is ongoing for patients in the 0.45 mg/kg and 0.6 mg/kg cohorts with plans to initiate an expansion cohort in 2024.
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