NTLA-2001 Gene Editing Trial to Include Patients With Heart Disease

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A clinical trial of the gene-editing therapy NTLA-2001 in people with familial amyloid polyneuropathy (FAP) is expanding to include those with a related condition, called ATTR amyloidosis with cardiomyopathy (ATTR-CM), Intellia Therapeutics, which is developing the therapy, reported.

FAP is a form of ATTR amyloidosis — a group of disorders caused by the buildup of protein clumps, called amyloids, made up of a misfolded version of the protein transthyretin. FAP is characterized by neurological symptoms (polyneuropathy) and is caused by mutations in the TTR gene that provides instructions for making transthyretin.

ATTR-CM is a form of heart disease that results from the buildup of transthyretin amyloid deposits. ATTR-CM can be caused by TTR mutations, in which case it is known as hereditary ATTR-CM or ATTRv-CM, or it can occur in people with no mutations and is referred to as wild-type cardiomyopathy (ATTRwt-CM).

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The amendment to the Phase 1 study (NCT04601051) allows for enrollment of up to 36 adults with ATTR-CM in the U.K. The trial is open to adults with either ATTRv-CM or ATTRwt-CM who have New York Heart Association Class I–III heart failure — essentially encompassing all patients who have heart failure, but don’t have symptoms at rest.

“ATTR amyloidosis is a chronic, fatal disease that can impact different organs and tissues within the body, often manifesting as either polyneuropathy or cardiomyopathy. At Intellia, our goal is to develop a potentially curative treatment that could benefit as many patients living with this disease as possible,” John Leonard, MD, the company’s president and CEO, said in a press release.

NTLA-2001 is a one-time gene editing therapy, delivered by infusion into the bloodstream, that aims to disrupt the TTR gene in liver cells, the main producers of transthyretin, to lower the protein’s levels in the body. According to Intellia, this could halt or even reverse disease progression.

NTLA-2001 has been designated an orphan drug in the U.S. and Europe.

The main goal of Intellia’s ongoing Phase 1 trial is to evaluate the safety, tolerability, and pharmacological properties of the experimental therapy. Secondary goals include assessing the effect of treatment on transthyretin levels and symptoms.

The trial is recruiting FAP patients at sites in New Zealand, Sweden, and the U.K. Data from the first six participants, announced earlier this year, indicated that single treatment with NTLA-2001 safely and rapidly lowered transthyretin levels in a dose-dependent manner.

“We have already seen promising interim data supporting the ability of NTLA-2001 to significantly reduce serum TTR levels in ATTR patients with polyneuropathy,” Leonard said. “We are excited to now expand our Phase 1 study of NTLA-2001 to include ATTR patients with cardiomyopathy in order to advance this potentially first-of-its-kind, single-dose treatment for more patients.”