In a December 13 press release listed on the company’s website, genome editing company Intellia Therapeutics, Inc. (“Intellia”) shared that the first patient had been dosed in a Phase 1/2 clinical trial evaluating NTLA-2002 for hereditary angioedema (HAE). Reaching this point is exciting, especially as NTLA-2002 is the first single-dose gene-editing therapy of its kind that has made it to clinical trials.

NTLA-2002

To begin, let’s take a look at what NTLA-2002 is. According to Intellia, NTLA-2002 is designed to reduce HAE attacks, which usually occur every 7-14 days in untreated patients. The therapy, which uses CRISPR/Cas9 gene-editing technology:

employs a knockout edit of KLKB1 gene in hepatocytes [and] aims to reduce plasma kvllikrein activity to prevent excess bradykinin production leading to HAE attacks after a single course of treatment.

NTLA-2002 is administered intravenously and uses lipid nanoparticles for the most effective delivery. Now, researchers seek to evaluate NTLA-2002 in a Phase 1/2 clinical trial. During the trial, researchers will explore the safety, efficacy, tolerability, and pharmacokinetic and pharmacodynamic profile of the treatment for patients with HAE. Within this study, researchers will also figure out what dosage to use when performing further research.

Hereditary Angioedema (HAE)

SERPING1 gene mutations most commonly cause types 1 and 2 hereditary angioedema (HAE). HAE is aptly named: hereditary (inherited), angio (pertaining to blood vessels), edema (swelling causes by excess fluid). In patients with HAE, severe, unexplained “attacks” occur of swelling underneath the skin. Because HAE is inherited in an autosomal dominant pattern, patients must inherit only one defective gene to have this condition. However, in some cases, HAE results from a spontaneous mutation.

Regardless, these mutations cause C1-inhibitor, a blood protein, to either work poorly or not work at all. Normally, C1-inhibitor plays a part in coagulation and inflammation. However, when this protein doesn’t work correctly, excess protein fragments called bradykinin build up and cause inflammation. HAE attacks can also be triggered by stress, injuries, alcohol use, or without a known cause. While both men and women can have HAE, women are more often affected. Symptoms include:

• Arms, legs, hands, and toes swelling to 2x+ their original size
• Swollen lips, cheeks, and eyelids
• Abdominal pain
• Nausea and vomiting
• Abdominal distention
• Larynx, esophagus, or tracheal swelling, which may cause difficulty breathing