Phase 2 trial of NTLA-2002, HAE gene-editing therapy, to enroll in US

One-time hereditary angioedema treatment showing early safety, efficacy

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) has given Intellia Therapeutics permission to open U.S. sites in its ongoing clinical trial of NTLA-2002, an investigational gene-editing therapy for hereditary angioedema (HAE).

Specifics are not yet available on the number or location of U.S. sites for the global Phase 2 portion of the trial, which is evaluating the safety and potential efficacy of the company’s one-time treatment to prevent HAE attacks.

“The FDA’s acceptance of our … application to initiate clinical evaluation of NTLA-2002 brings us one step closer to introducing a potentially paradigm-shifting treatment for people living with hereditary angioedema,” John Leonard, MD, president and CEO of Intellia, said in a company press release. “We are thrilled to advance the development of NTLA-2002 in the U.S.”

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Phase 2 trial will test NTLA-2002 against a placebo in patients

In HAE, swelling attacks are triggered by the overproduction of a signaling molecule called bradykinin. The production and release of this signaling molecule is controlled by a protein called kallikrein.

NTLA-2002 is designed to reduce kallikrein levels, thus lowering bradykinin levels to prevent swelling. The therapy uses gene-editing technology to disrupt the activity of the KLKB1 gene, which provides instructions for making a precursor of the kallikrein protein. Less of the precursor, prekallikrein, being made results in lower kallikrein levels.

Intellia opened a Phase 1/2 clinical trial (NCT05120830) into the safety, pharmacological properties and early efficacy of NTLA-2002 in adults with HAE types 1 and 2 in late 2021.

In the open-label Phase 1 portion, participants were given a single infusion of NTLA-2002 at one of three doses, 25, 50, and 75 mg. Interim data covering 10 participants, collected over at least 16 weeks (about four months) and released in November, indicated that the therapy was generally well tolerated and lowered swelling attack rates. All trial patients are being followed for up to 104 weeks, about two years.

The study’s Phase 2 portion will test two doses of NTLA-2002, given as a one-time infusion, against a placebo. Its main goal, in addition to treatment safety and tolerability, is changes in rates of HAE swelling attacks at 16 weeks post-infusion. Secondary goals include changes in blood plasma levels of kallikrein.

Patient screening for this Phase 2 part recently began at sites outside the U.S., Intellia announced.

“We are thrilled to advance the development of NTLA-2002 in the U.S. and are working to rapidly enroll patients in the Phase 2 portion of the study,” Leonard said. “We look forward to presenting additional data from the first-in-human, Phase 1 portion of the study later this year.”