Verve Therapeutics announced the lifting of the clinical hold and clearance of its IND application by the U.S. FDA, clearing the way for the company to conduct a clinical trial in the U.S. evaluating VERVE-101 for the treatment of heterozygous familial hypercholesterolemia (HeFH).
HeFH is a relatively common genetic disorder characterized by dangerously elevated levels of low-density lipoprotein cholesterol. It’s an autosomal dominant disorder, and only one parent needs to have an LDLR gene mutation for it to be expressed in offspring. VERVE-101, a single-course, in vivo liver gene editing treatment, uses a lipid nanoparticle-mediated delivery to make a single base change at the site of the affected gene.
The FDA placed the initial hold on Boston-based Verve's IND last November, requesting that Verve provide additional information to resolve the clinical hold, specifically more data about the possible risks of accidental germline editing. The agency also requested more data concerning potency differences between human and non-human cells as well as off-target analyses in non-hepatocyte cell types.
To resolve the hold, Verve submitted interim clinical data from the dose-escalation portion of the ongoing heart-1 phase 1b clinical trial and addressed the FDA’s preclinical questions. The heart-1 trial is evaluating the safety, tolerability, pharmacokinetic and pharmacodynamic profile of VERVE-101 in patients with HeFH, and is currently being conducted at sites in the UK and New Zealand.
With the hold lifted, Verve says it plans to begin the process of activating U.S. clinical trial sites for the heart-1 trial.
