Intellia Therapeutics has announced positive results from its Phase I/II trial of NTLA-2002, a CRISPR-based gene editing therapy for hereditary angioedema (HAE). The data indicate a significant reduction in attack rates among patients treated with NTLA-2002 compared to those receiving a placebo.
NTLA-2002 leverages CRISPR/Cas9 technology to inactivate the kallikrein B1 (KLKB1) gene, which is responsible for producing prekallikrein, a precursor protein linked to HAE. The therapy is designed as a one-time intravenous infusion to provide long-term control of HAE symptoms.
Phase II Trial Details and Results
The Phase II double-blind, randomized, placebo-controlled trial assessed the safety, efficacy, pharmacodynamics, and pharmacokinetics of NTLA-2002. Twenty-seven participants were randomized to receive either a 25mg or 50mg dose of NTLA-2002 or a placebo.
Data from the trial, with a cutoff date of April 4, 2024, showed notable reductions in mean monthly attack rates in patients treated with NTLA-2002 compared to placebo. Specifically, the 25mg and 50mg doses resulted in a 75% and 77% reduction in attack rates during the first 16 weeks, improving to 80% and 81% during weeks five to 16, respectively.
In the 50mg cohort, eight out of eleven patients achieved a complete response, experiencing no attacks throughout the 16-week observation period. In comparison, the 25mg cohort saw four out of ten patients experiencing a complete response, while no patients in the placebo group achieved this outcome.
Impact on Kallikrein Protein Levels
Patients receiving the 50mg dose also exhibited a greater reduction in kallikrein protein levels, with an 86% mean reduction from baseline at week 16, compared to a 55% reduction in the 25mg group. The therapy was well tolerated at both dosage levels.
Future Directions
Based on these positive outcomes, Intellia has selected the 50mg dose for further evaluation in the global, pivotal Phase III HAELO study, which is currently screening patients. This study will further assess the efficacy and safety of NTLA-2002 in a larger patient population.
Executive Perspective
Intellia President and CEO John Leonard stated, "These positive NTLA-2002 Phase II results underscore the tremendous potential of our in vivo CRISPR gene editing therapy to be a functional cure and redefine the treatment paradigm for HAE. We are highly encouraged by these results, which we believe sets NTLA-2002 apart from other prophylaxis treatments."
