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 trial's findings suggest that NTLA-2002 could offer a functional cure for this rare genetic condition characterized by severe swelling attacks. The therapy leverages CRISPR/Cas9 technology to inactivate the kallikrein B1 (KLKB1) gene, which is responsible for producing prekallikrein, a precursor protein linked to HAE.
Phase II Trial Results
The Phase II double-blind, randomized, placebo-controlled trial evaluated 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 via intravenous infusion. Data, which was cut off on April 4, 2024, showed a significant reduction in mean monthly attack rates in patients treated with NTLA-2002 compared to placebo.
According to Intellia, 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. Notably, in the 50mg cohort, eight out of 11 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 did.
Impact on Kallikrein 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. These results indicate a dose-dependent effect on the target protein, suggesting that higher doses may provide more effective control of HAE symptoms.
Safety and Tolerability
The therapy was observed to be well-tolerated at both dosage levels, supporting its potential as a safe and effective treatment option for HAE. This is particularly important for a condition that currently relies on chronic prophylactic treatments or on-demand therapies to manage acute attacks.
Path to Phase III
Based on these positive outcomes, Intellia has selected the 50mg dose for further evaluation in the global, pivotal Phase III HAELO study, which began screening patients earlier this month. This Phase III trial will further assess the efficacy and safety of NTLA-2002 in a larger patient population, with the goal of securing regulatory approval and bringing this innovative therapy to market.
Management Commentary
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."
