Intellia Therapeutics announced positive Phase 2 data for NTLA-2002, an investigational CRISPR-based gene editing therapy, indicating its potential as a one-time functional cure for hereditary angioedema (HAE). The study, published in The New England Journal of Medicine, revealed that a single 50 mg dose led to a mean monthly attack rate reduction of 77% and 81% compared to placebo during weeks 1-16 and 5-16, respectively. These findings suggest a significant advancement in HAE treatment, potentially eliminating the need for chronic therapies.
NTLA-2002: A Potential Paradigm Shift in HAE Treatment
HAE is a rare genetic condition affecting an estimated one in 50,000 people, characterized by severe, recurring swelling attacks. Current treatments often require lifelong administration and may not completely eliminate attacks. NTLA-2002 offers a novel approach by targeting the KLKB1 gene, which encodes for prekallikrein, a kallikrein precursor protein, using CRISPR/Cas9 technology.
"These positive NTLA-2002 Phase 2 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," said Intellia President and Chief Executive Officer John Leonard, M.D.
Phase 2 Trial Results: Efficacy and Safety
The Phase 2 study was a randomized, double-blind, placebo-controlled trial involving 27 participants. Patients received either a 25 mg or 50 mg dose of NTLA-2002 or a placebo. The data cutoff was April 4, 2024, with the 25th patient completing the 16-week primary observation period.
Key findings include:
- In the 50 mg arm, 8 out of 11 patients experienced a complete response, remaining attack-free throughout the 16-week observation period and subsequent follow-up (median of eight months).
- Patients receiving the 50 mg dose achieved an 86% mean reduction in kallikrein protein from baseline at week 16, compared to a 55% reduction in the 25 mg arm.
- The therapy was generally well-tolerated, with the most common adverse events being headache, fatigue, and nasopharyngitis. All adverse events were Grade 1 or 2, except for one serious adverse event (Grade 4 edema of the tongue with breathing impairment) in the placebo arm, attributed to the patient's underlying HAE.
Path to Phase 3 and Potential Approval
Based on these promising results, Intellia has initiated a global, pivotal Phase 3 HAELO study to further evaluate the 50 mg dose of NTLA-2002. This trial is actively screening patients, marking a significant step towards potential regulatory approval and widespread availability of this innovative therapy.
"These NTLA-2002 Phase 2 data are remarkable, showing this investigational therapy could permanently stop swelling attacks with a single infusion," said Danny Cohn, M.D., Ph.D., lead principal investigator of the Phase 2 study. "I am optimistic that NTLA-2002 will change the way we treat HAE and put an end to the need for a lifetime of chronic treatment."
