Gene-Editing Therapy Shows Promise in Hereditary Angioedema

A single dose of the CRISPR-based gene-editing therapy NTLA-2002 significantly reduced angioedema attacks compared with placebo in patients with hereditary angioedema, according to results from a phase II randomized study presented at the recent American College of Allergy, Asthma & Immunology (ACAAI) annual meeting.

In this exclusive MedPage Today video, study author Danny M. Cohn, MD, PhD, of Amsterdam University Medical Center, discusses the results of the study.

Following is a transcript of his remarks:

What I presented was the phase II data of this clinical study program, which was a randomized, double-blind, placebo-controlled portion of the study in which patients were allocated to either placebo or 25 mg or 50 mg of NTLA-2002.

They were required to wash out any long-term prophylactic therapy prior to enrollment and through the end of the 16-week primary observation. But they could restart after that time.

The primary endpoint in phase II was the number of angioedema attacks per month during the primary observation period from weeks 1 to 16, and analysis occurred when the 25th patient reached the 16-week time period. Data cutoff was April 4th, 2024. And other key secondary endpoints included safety, the number of angioedema attacks per month from weeks 5 to 16, and change from baseline in total plasma kallikrein protein level.

A total of 27 patients were dosed and, notably, the baseline monthly angioedema attack rate was similar across all arms. And patients’ age range was between 18 to 76 years of age.

During the primary observation period, which lasted between weeks 1 to 16, the mean monthly attack rate relative to placebo was reduced by 75% for those patients allocated to 25 mg, and 77% for patients allocated to the 50-mg dose of NTLA-2002. The mean monthly angioedema attack rate during weeks 5 to 16 was reduced by 80% and 81%, respectively. Overall, NTLA-2002 led to reduced levels of attack rate reduction at both doses.

And when we look at the response rate, a total of eight out of 11 patients had a complete response, which is 73%, which meant that they were completely attack free following the dosing of NTLA-2002 — and that compared to four out of 10 patients receiving 25 mg, so 40%, and none of the patients receiving placebo. The patients that had a complete response did not require any subsequent treatment for hereditary angioedema.

NTLA-2002 was well tolerated, which is consistent also with observations from the phase I portion of the study. And these data supported the selection of the 50-mg dose for assessment in the randomized, double-blind, placebo-controlled phase III trial, which is currently recruiting.

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