Precision's one-time gene editing treatment lowers cholesterol in monkeys for 3 years

heart model
Precision BioSciences' treatment could offer an alternative to fighting heart disease with PCSK9-lowering drugs like Amgen’s Repatha as well as Sanofi and Regeneron’s Praluent, researchers said. (Pixabay)

Precision BioSciences was founded in 2006 to develop a genome editing technology that uses homing nucleases to make precise edits in DNA. Now, the company has preclinical evidence showing that the approach—designed as a one-time treatment—holds promise for treating familial hypercholesterolemia, high cholesterol that’s caused by abnormalities in the gene PCSK9.

A single dose of Precision’s treatment reduced the expression of PCSK9, resulting in a stable lowering of LDL cholesterol in nonhuman primates for three years, according to a study led by the University of Pennsylvania and published in the journal Molecular Therapy. The treatment reduced PCSK9 protein levels by 85% and LDL cholesterol levels by 56%.

Precision is developing the technique, called ARCUS nuclease gene editing, as an alternative to drug treatments for familial hypercholesterolemia, including Amgen’s Repatha as well as Sanofi and Regeneron’s Praluent.

“These results not only contribute to the growing evidence of gene editing for potential therapeutic use, but specifically showed that ARCUS nuclease gene editing could be a very promising new approach leading to treatments for heart disease patients that do not tolerate commonly used PCSK9 inhibitors,” said lead author James Wilson, M.D., Ph.D., a professor and director of the Penn Gene Therapy Program and the Penn Orphan Disease Center, in a statement.

RELATED: JPM: Verve Therapeutics unveils its lead program—a one-and-done treatment for genetic high cholesterol

Precision’s ARCUS uses nucleases that are designed to either insert, delete or fix specific sequences of DNA. The company’s lead program is an off-the-shelf CAR-T for leukemia and lymphoma that’s partnered with Servier and currently in clinical trials.

In November, Precision inked another deal, with Eli Lilly, which handed the company $100 million upfront to develop in vivo gene therapies for three targets, including Duchenne muscular dystrophy. Lilly also pumped a $35 million investment into Precision and vowed up to $420 million in development and commercialization milestone payments.

Precision does have some competition in the cholesterol arena. At the annual J.P. Morgan healthcare conference, two-year-old Verve Therapeutics revealed that its lead program is a base editor that blocks the PCSK9 gene. It’s also a one-time treatment, designed to change just one base in the genome.

Verve reported last June that in monkeys, the treatment prompted an 89% drop in PCSK9 and a 59% lowering of LDL cholesterol in two weeks. The company is now following the animals to determine the long-term efficacy of the treatment.

Precision also plans to continue its monitoring of the nonhuman primates in its trial in the hopes of gaining insights into its other ARCUS programs. Chief Scientific Officer Derek Jantz, Ph.D., said the three-year results of the cholesterol study provide hope gene editing could be a viable long-term solution to familial hypercholesterolemia.

“At more than three years out, we are seeing a stable gene edit that is being inherited by subsequent generations of hepatocytes, and evidence thus far supports that this is a permanent change,” Jantz said.