A new investigational clustered regularly interspaced short palindromic repeats (CRISPR)/Cas 9 gene-editing therapy for the treatment of hereditary angioedema (HAE) has received Orphan Drug designation from the US Food and Drug Administration (FDA). 

This is an important milestone for the development of the drug candidate, as it can speed up its approval and entry into the market if approved.

“Orphan drug designation . . . underscores the importance of developing innovative, new treatment options for people living with HAE,” John Leonard, MD, the president and chief executive officer of Intellia Therapeutics, the developers of the treatment, said in a press release.

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The experimental treatment, called NTLA-2002, is currently being tested in a phase 1/2 clinical trial to investigate its safety, tolerability, pharmacokinetics, and pharmacodynamics in an estimated 55 patients with type 1 or type 2 HAE, aged 18 or more years. 

Read more about the pathophysiology of HAE

In the open-label, single-ascending dose phase 1 portion of the study, several dose levels of NTLA-2002 will be tested. Then, up to 2 dose levels will be further tested in the randomized, placebo-controlled phase 2 part. 

The trial is still recruiting participants in the Netherlands, New Zealand, and the United Kingdom, and it is estimated to be completed on December 15, 2025. 

NTLA-2002 is an in vivo genome-editing candidate designed to knock out the kallikrein B1 (KLKB1) gene to reduce the amount of prekallikrein in the plasma, thereby reducing the activity of kallikrein. Kallikrein plays a crucial role in vasodilation and the transfer of excess fluid to the tissues, resulting in angioedema attacks.

HAE is a rare disease affecting around 1 in every 50,000 people. Type 1 disease, which is the most common form, is caused by a deficiency in C1 inhibitor (C1-INH), while type 2 is the result of dysfunctional C1-INH protein.


Intellia Therapeutics receives U.S. FDA Orphan Drug designation for NTLA-2002, an investigational CRISPR therapy for the treatment of hereditary angioedema. News release. Intellia Therapeutics, Inc; September 1, 2022.

NTLA-2002 in adults with hereditary angioedema (HAE) (NTLA-2002). ClinicalTrials.gov. November 15, 2021. Updated July 20, 2022. Accessed September 9, 2022.