HAE Gene-editing Therapy Earns Orphan Drug Status

The FDA designation provides incentives to Intellia Therapeutic's NTLA-2002

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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NTLA-2002, an experimental gene-editing therapy designed to prevent swelling attacks in people with hereditary angioedema (HAE), has been granted orphan drug status by the U.S. Food and Drug Administration (FDA).

This designation is given to investigational treatments that have the potential to improve care for rare diseases, defined as those affecting fewer than 200,000 people in the U.S. The designation qualifies NTLA-2002’s developer — Intellia Therapeutics — for certain incentives, including tax credits, fee exemptions, and a guarantee of seven years’ market exclusivity if the therapy is ultimately approved.

“Orphan drug designation represents an important milestone in the development of NTLA-2002 and underscores the importance of developing innovative, new treatment options for people living with HAE,” John Leonard, MD, Intellia’s president and CEO, said in a press release.

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In HAE, swelling attacks are driven by abnormally high levels of a signaling molecule called bradykinin. A protein called kallikrein controls the production and release of this signaling molecule. NTLA-2002 is a one-time treatment designed to reduce kallikrein levels — thereby lowering bradykinin levels and reducing the risk of swelling attacks — using the gene-editing system CRISPR/Cas-9.

CRISPR/Cas-9 components are wrapped in lipid nanoparticles, which are tiny spheres of fatty molecules that can deliver the gene-editing machinery to cells in the liver. These gene-editing components are designed to disrupt the activity of the KLKB1 gene, which provides instructions for making a precursor of the kallikrein protein.

Intellia is sponsoring a first-in-human Phase 1/2 clinical trial (NCT05120830) that is testing NTLA-2002 in people with HAE. The trial is open to adults with HAE types 1 or 2; it is recruiting at sites in New Zealand, the Netherlands, and the U.K.

In the Phase 1 portion, participants are given a single infusion of NTLA-2002 at one of three doses. The lowest dose group (25 mg) completed dosing earlier this year, and the study is currently recruiting participants for the medium dose group (75 mg). The Phase 2 portion is planned to compare NTLA-2002 against a placebo.

“We hope to demonstrate in our ongoing clinical trial that NTLA-2002 can result in deep and sustained kallikrein activity reduction following a single dose, and potentially prevent the unpredictable swelling attacks caused by this genetic disease,” Leonard said. He added that interim data from the trial will be presented later this month at the 2022 Bradykinin Symposium.