PHILADELPHIA – The first in-human study of a gene therapy designed to reduce low-density lipoprotein cholesterol has shown a signal that the treatment works in a small group of patients with heterozygous familial hypercholesterolemia (HeFH).
While one of four patients in the highest-dose groups had a myocardial infarction the day after getting the treatment, investigators have enough confidence to go forward with the next phase of study.
"The HEART-1trial demonstrated the first human proof of concept for in vivo DNA-based editing," said Andrew Bellinger, MD, PhD, chief scientific officer of Verve Therapeutics, the company developing the treatment. "We saw dose-dependent–based reductions in LDL and the PCSK9 protein."
The HEART-1 study was a phase 1b trial of VERVE-101, a CRISPR-based gene editing mechanism designed to inactivate the liver gene PCSK9, which contributes to raising cholesterol. "Human genetics suggest that turning off the cholesterol-raising gene PCSK9 in the liver will durably reduce LDL cholesterol," Dr. Bellinger said in presenting the results at the annual scientific sessions of the American Heart Association.
Lipid nanoparticle
VERVE-101 is designed to be a single-course treatment to specifically treat HeFH, Dr. Bellinger said. He explained how the therapy, given by intravenous infusion, differs from adeno-associated virus vectors that have dominated gene therapy platforms.
