Intellia Trial to Test Gene-editing Therapy NTLA-2002 in New Zealand

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

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The New Zealand Medicines and Medical Devices Safety Authority has authorized Intellia Therapeutics to launch a Phase 1/2 trial testing NTLA-2002, its investigational gene-editing therapy, in adults with hereditary angioedema (HAE).

According to the company, patient enrollment is expected to start by the end of the year.

Data from this trial will be used to determine the best doses of NTLA-2002 for future studies, according to Intellia.

“We look forward to initiating this year our first-in-human study of NTLA-2002 for people living with HAE, a debilitating disorder that causes frequent, potentially life-threatening attacks,” Jon Leonard, MD, president and CEO of Intellia said in a press release.

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HAE is a rare form of angioedema in which fluid leaks from blood vessels into the surrounding tissue, causing swelling. These swelling episodes also are accompanied by pain and inflammation. The disease is characterized by the overproduction of bradykinin, an inflammatory molecule that promotes blood vessel widening and permeability.

NTLA-2002 uses the CRISPR/CAS9 gene-editing technology, which enables researchers to target and change specific genes, to completely remove a gene called KLKB1 from liver cells. This gene provides instructions for making prekallikrein, a precursor of kallikrein, which in turn is a precursor of bradykinin.

By eliminating this gene from liver cells, NTLA-2002 is expected, after a single treatment, to lower bradykinin levels, and thereby reduce or prevent HAE attacks.

“We believe NTLA-2002 has the potential to be a curative therapy for patients with HAE by providing continuous suppression of plasma kallikrein activity following a single dose and eliminating the significant treatment burden associated with currently available HAE therapies,” said Leonard.

In preclinical studies, NTLA-2002 reduced kallikrein activity by about 90% for at least 11 months in non-human primates.

The new Phase 1/2 trial will help determine the safety and tolerability of NTLA-2002, and the way in which the medication is metabolized, or broken down, within the body. It will enroll adults with type 1 and type 2 HAE. During the study, investigators will measure both kallikrein levels and activity.

The study comprises two different phases. The Phase 1 portion follows an open-label, single increasing dose part that will determine the best doses — up to two different amounts — to be used in the second part of the study, in which NTLA-2002 will be tested against a placebo.

In addition to New Zealand, Intellia is planning trials in other countries. The company will be submitting those regulatory applications as part of NTLA-2002’s global development program.