NTLA-2001 Shows Benefits for ATTR Patients With Heart Disease
One-time gene-editing therapy led to sustained reductions in toxic TTR levels
One-time treatment with the experimental gene-editing therapy NTLA-2001 led to substantial reductions in the levels of toxic transthyretin protein that were sustained for several months in people with ATTR amyloidosis with cardiomyopathy (ATTR-CM).
That is according to data shared by NTLA-2001’s co-developer, Intellia Therapeutics, at the American Heart Association (AHA) Scientific Sessions 2022, held earlier this month, in Chicago, Illinois. The late-breaking oral presentation was titled “First-in-Human in vivo CRISPR/Cas9 Editing of the TTR Gene by NTLA-2001 in Patients with Transthyretin (ATTR) Amyloidosis with Cardiomyopathy.”
“This presentation at the AHA Scientific Sessions marks the first time Intellia has had the opportunity to share interim data from our landmark clinical trial of NTLA-2001 for the treatment of ATTR amyloidosis with the cardiology community,” John Leonard, MD, Intellia’s president and CEO, said in a press release.
TTR builds up and damages heart tissue in people with ATTR-CM
ATTR amyloidosis refers to a group of diseases caused by the buildup of toxic aggregates or clumps made up of a protein called transthyretin (TTR). Familial amyloid polyneuropathy (FAP) is a specific form of ATTR amyloidosis that is caused by mutations in the gene that provides instructions for making the TTR protein and is mainly characterized by nerve damage. In ATTR-CM, TTR builds up and damages heart tissue.
NTLA-2001 is a gene-editing therapy that is essentially designed to disrupt the gene that encodes the TTR protein specifically in liver cells — the main producers of TTR in the body — thereby halting TTR production and reducing the buildup of toxic protein aggregates that drive disease symptoms. Intellia is co-developing NTLA-2001 with Regeneron Pharmaceuticals.
Intellia is sponsoring a Phase 1 trial (NCT04601051) to explore the safety and preliminary efficacy of NTLA-2001 in people with FAP or ATTR-CM. The trial is expected to be fully enrolled by the end of the year, according to Intellia.
With the depth and consistency of TTR protein reduction seen with NTLA-2001 thus far, we envision a future where physicians and patients can make treatment decisions based on a therapy’s ability to achieve specific threshold protein levels
At the meeting, researchers presented interim data from 12 people with ATTR-CM who were treated with NTLA-2001. All identified as male, and most were in their 70s.
Nine patients were given a dose of 0.7 mg/kg; among them, three had relatively mild heart disease and the other six had more severe heart disease. The other three patients, all with milder heart disease, received a dose of 1 mg/kg.
At one month post-dosing, the mean level of TTR protein had fallen by more than 90% in all groups — 92%–94% with the lower dose and 92% with the higher one.
Decreases in toxic TTR levels were sustained during follow-up
All patient dosing groups had TTR data available up to four months post-dosing, and these decreases were sustained through the entire follow-up period. Decreases also were sustained up to six months among patients with available data.
Similar reductions were previously reported among FAP patients in the trial.
“With the depth and consistency of TTR protein reduction seen with NTLA-2001 thus far, we envision a future where physicians and patients can make treatment decisions based on a therapy’s ability to achieve specific threshold protein levels,” Leonard said. “We look forward to progressing this first-ever systemically administered in vivo CRISPR [gene editing] investigational therapy toward completion of the Phase 1 study and subsequent pivotal studies in collaboration with our partners at Regeneron.”
NTLA-2001 was generally well-tolerated; there were no clinically significant laboratory findings, and most reported safety-related events were mild in severity. The only side effects deemed definitely related to treatment were two infusion reactions, one of which was graded as severe.