A single dose of the CRISPR-based gene-editing therapy NTLA-2002 significantly reduced angioedema attacks compared with placebo in patients with hereditary angioedema. These findings come from a phase II randomized, double-blind, placebo-controlled study presented at the American College of Allergy, Asthma & Immunology (ACAAI) annual meeting. The results suggest a potentially transformative treatment option for individuals suffering from this debilitating condition.
The study, led by Danny M. Cohn, MD, PhD, of Amsterdam University Medical Center, involved patients who were administered either placebo, 25 mg, or 50 mg of NTLA-2002. Participants were required to wash out any long-term prophylactic therapy before enrollment and throughout the 16-week primary observation period, but could restart treatment after that time. A total of 27 patients were dosed, with ages ranging from 18 to 76 years.
The primary endpoint of the phase II trial was the number of angioedema attacks per month during the primary observation period (weeks 1 to 16). 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. The data cutoff for the analysis was April 4th, 2024.
Significant Reduction in Angioedema Attacks
During the primary observation period, the mean monthly attack rate relative to placebo was reduced by 75% for patients receiving 25 mg of NTLA-2002 and 77% for those receiving the 50-mg dose. Furthermore, the mean monthly angioedema attack rate during weeks 5 to 16 was reduced by 80% and 81%, respectively, for the two dose groups. These results indicate a substantial reduction in attack rates with NTLA-2002 at both doses.
Complete Response and Tolerability
Notably, eight out of 11 patients (73%) in the 50mg dose group experienced a complete response, meaning they were completely attack-free following the dosing of NTLA-2002. In comparison, four out of 10 patients (40%) receiving 25 mg achieved a complete response, while none of the patients in the placebo group did. Patients who had a complete response did not require any subsequent treatment for hereditary angioedema.
NTLA-2002 was reported to be well-tolerated, consistent with observations from the phase I portion of the study. This favorable safety profile, combined with the efficacy 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 patients.
