Interim Trial Data of Gene-editing Therapy NTLA-2001 Expected This Year

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Intellia Therapeutics anticipates reporting interim data this year from a Phase 1 study evaluating the safety and activity profile of NTLA-2001, its investigational gene-editing therapy to treat hereditary transthyretin amyloidosis with polyneuropathy, also known as familial amyloid polyneuropathy (FAP).

Last year, Intellia dosed the first patient in the trial (NCT04601051), which is currently recruiting participants in London, U.K., and Auckland, New Zealand. The trial is expected to enroll approximately 38 adults who have no access to approved treatments or whose disease progressed despite treatment.

Intellia, which co-developed NTLA-2001 along with Regeneron Pharmaceuticals, is currently submitting additional regulatory applications in other countries as part of its global strategy.

NTLA-2001 uses the CRISPR/Cas9 gene-editing technology, which is derived from a bacterial defense mechanism and allows specific DNA regions to be added, removed, or edited in a gene.

“Dosing our first patient with NTLA-2001, the first-ever systemically delivered CRISPR-based therapy, was a major milestone for our team,” John Leonard, MD, president and CEO of Intellia, said in a press release.

“We have made steady progress in our global Phase 1 study of NTLA-2001 and look forward to sharing our first clinical data this year,” he added. 

FAP is caused by mutations in the TTR gene that render the TTR protein it encodes very unstable and likely to form toxic clumps (amyloids) that accumulate in different tissues and organs, gradually damaging and impairing their function.

NTLA-2001 is designed to eliminate the TTR gene from patient liver cells, which is expected to help delay or even prevent tissue and organ damage. The therapy is delivered to patient liver cells through a non-viral, lipid nanoparticle system, and is expected to provide long-lasting effects with a single administration.

In addition to FAP, NTLA-2001 is also being developed to treat wild-type ATTR, a more common form of the disease that is not associated with any known genetic mutations.

The Phase 1 study was supported by preclinical studies in non-human primates, which showed that a single dose of NTLA-2001 was able to lower TTR protein levels by more than 95%. These reductions in TTR protein levels were considered clinically meaningful and were sustained for at least one year. 

Along with safety and tolerability, the study will evaluate how the therapy moves through the body (pharmacokinetics), as well as the effects it has (pharmacodynamics). 

In the first portion of the trial, participants will receive increasing doses of NTLA-2001 to find the safest and more effective dose to be used.

An open-label extension will then test these established doses in a broad population of patients with ATTR, including those in whom the disease is associated with both nerve and heart damage. During this part of the study, an initial assessment of the therapy’s effects will be done, along with a characterization of its activity and additional safety information.

Intellia is also using its gene-editing technology to advance therapies for specific subtypes of acute myeloid leukemia (AML), a type of blood cancer, and hereditary angioedema (HAE), a disorder that causes sudden and recurrent bouts of swelling that affect the deep layers of the skin. 

“Intellia’s achievements in 2020 reflect important progress on both our full-spectrum strategy and our mission to deliver curative genome editing treatments for people with severe diseases,” said Leonard.

“Additionally, we are on track to submit first-in-human regulatory applications to begin clinical studies of NTLA-5001 for AML and NTLA-2002 for HAE, and we plan to nominate at least one new development candidate from our research portfolio.”