A rare genetic condition known as hereditary angioedema (HAE) causes severe, sporadic swelling attacks in a variety of body organs and tissues. These swelling attacks can be excruciatingly painful, incapacitating, and even fatal. A new study demonstrating the success of a treatment employing the CRISPR therapy technology is being presented at the American College of Allergy, Asthma, and Immunology (ACAAI) Annual Scientific Meeting this year in Louisville, Kentucky.
According to clinical immunologist Hilary Longhurst, MD, PhD, the primary author of the paper, “NTLA-2002 is a one-time, systemically administered CRISPR therapy candidate being explored for HAE.” “It is designed to knock out the KLKB1 gene in liver cells, lowering the production of a particular protein called kallikrein, whose unregulated activity is responsible for the recurrent, disabling, and perhaps fatal swelling events that occur in persons with HAE,” according to the study.
The Phase 1 first-in-human study of NTLA-2002 interim clinical data, specifically for the patients with HAE (both men and women) treated to date at escalating dosages of 25 mg, 50 mg, and 75 mg, is being presented at the ACAAI meeting this year.
All patients treated with a single dose of NTLA-2002 in the 25 and 75 mg dose groups experienced immediate and significant drops in plasma kallikrein levels, according to Danny Cohn, MD, the study’s main author. “All patients had a significant reduction in HAE attacks for the three individuals in the 25 mg dose cohort who reached a predetermined time point where their HAE attacks were examined.”
NTLA-2002 was generally well tolerated at both the 25 and 75 mg dose levels, and the majority of side effects were mild to moderate in severity. Infusion-related reactions were the most frequent adverse events; these reactions were typically Grade 1 and went away in a day. To present, no dose-limiting toxicities, grave adverse events, or Grade 3 or higher adverse events have been reported.
According to Dr. Longhurst, “These preliminary results support NTLA-2002 as a viable single-dose therapy to relieve HAE symptoms.” Clinical research for this program will continue, and the randomized Phase 2 of the clinical study is scheduled to start in the first half of 2023.
