The clustered regularly interspaced short palindromic repeats (CRISPR)-based genome-editing candidate NTLA-2002 leads to reductions in plasma kallikrein levels and hereditary angioedema (HAE) attacks, according to interim results from a phase 1/2 clinical trial presented at the 2022 Bradykinin Symposium in Berlin, Germany.

“These early data support NTLA-2002 as a potential one-time treatment capable of producing profound reductions in HAE attacks,” Hilary Longhurst, MD, PhD, the principal investigator of the trial in New Zealand, said in a press release. “While the clinical data are still emerging, I am highly optimistic that NTLA-2002 could become a new treatment option for the HAE community.”

NTLA-2002 was also generally well tolerated during the trial, according to Intellia Therapeutics, the developers of the experimental treatment.


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NTLA-2002 is a systemically administered CRISPR-based drug candidate designed to knock out the KLKB1 gene in liver cells, thereby reducing kallikrein production, the overactivity of which leads to an overproduction of bradykinin and subsequent swelling attacks that can be life-threatening.

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The phase 1/2 trial is testing the safety, tolerability, activity, pharmacokinetics, and pharmacodynamics of NTLA-2002 in 55 patients with HAE, aged 18 years and older, in the Netherlands, New Zealand, and the United Kingdom. Patients are given a single dose of either 25 mg or 75 mg of NTLA-2002 by intravenous infusion.

According to results from 6 initial patients, a single dose of 25 mg of NTLA-2002 led to a 65% reduction in mean plasma kallikrein levels at week 8, while a single dose of 75 mg led to a 92% reduction. 

Moreover, patients given the 25-mg dose of NTLA-2022 had a 91% reduction in HAE attacks through week 16. Corresponding data are not yet available for patients in the cohort receiving 75 mg. 

Most adverse events were mild for both doses, according to Intellia. There were no dose-limiting toxicities and no serious adverse events.

Based on these results, the company announced it will test a third, 50-mg dose as part of the ongoing dose-escalation portion of the study. Researchers will then select 1 or 2 doses to be tested in the phase 2, placebo-controlled, dose-expansion portion of the study, which is expected to start in the first half of 2023 and be expanded to other countries including the United States.

References

Intellia Therapeutics announces positive interim clinical data for its second systemically delivered investigational CRISPR candidate, NTLA-2002 for the treatment of hereditary angioedema (HAE). News release. Intellia Therapeutics, Inc; September 16, 2022.

NTLA-2002 in adults with hereditary angioedema (HAE) (NTLA-2002). ClinicalTrials.gov. November 15, 2021. Updated July 20, 2022. Accessed September 19, 2022.