Intellia Reports Positive Phase 2 Results for NTLA-2002 in Hereditary Angioedema (HAE)

Intellia Therapeutics, Inc., a prominent clinical-stage gene editing company renowned for its CRISPR-based therapies, recently announced promising Phase 2 data from its ongoing Phase 1/2 study of NTLA-2002 in individuals with hereditary angioedema (HAE). The results were published in The New England Journal of Medicine and will be presented at the 2024 American College of Allergy, Asthma & Immunology (ACAAI) Scientific Meeting.

NTLA-2002, an investigational gene editing therapy, is being developed as a one-time treatment designed to prevent the swelling attacks associated with HAE, a rare genetic condition. The Phase 2 study's results are highly encouraging, showcasing the therapy's potential to significantly reduce attack rates following a single dose. Specifically, patients who received a 50 mg dose of NTLA-2002 experienced a mean monthly attack rate reduction of 77% during weeks 1-16 and 81% during weeks 5-16 compared to placebo. Remarkably, eight out of 11 patients in the 50 mg group were completely attack-free following a one-time infusion through the latest follow-up.

John Leonard, M.D., President and CEO of Intellia, emphasized the significance of these results, stating that they demonstrate NTLA-2002's potential to revolutionize HAE treatment. He noted that these outcomes highlight the therapy's ability to achieve complete response in a majority of patients, distinguishing it from existing prophylactic treatments that often require chronic administration and do not entirely prevent attacks.

Dr. Danny Cohn, the lead principal investigator of the Phase 2 study, echoed Leonard's sentiments, calling the data "remarkable." He expressed optimism about NTLA-2002's ability to permanently stop swelling attacks with a single infusion, potentially eliminating the need for ongoing, chronic treatment.

The randomized, double-blind, placebo-controlled Phase 2 study enrolled 27 participants, who were administered either 25 mg or 50 mg doses of NTLA-2002 or a placebo. Data analysis revealed that the single 50 mg dose led to significant attack rate reductions, with 75% and 77% reductions in mean monthly attack rates for the 25 mg and 50 mg arms respectively during weeks 1-16, and 80% and 81% during weeks 5-16. Furthermore, eight patients in the 50 mg arm showed complete response with no attacks during the 16-week primary observation period, maintaining this status through the latest follow-up.

Regarding safety and tolerability, NTLA-2002 was well-received at both dose levels. Frequent adverse events included headache, fatigue, and nasopharyngitis, all of which were mild to moderate in severity. Importantly, there were no serious adverse events attributed to NTLA-2002, and no significant laboratory abnormalities were noted.

Given these promising results, Intellia is moving forward with evaluating the 50 mg dose in the global, pivotal Phase 3 HAELO study, which is currently screening patients. This study aims to further establish NTLA-2002's efficacy and safety as a potential functional cure for HAE.

NTLA-2002 is based on CRISPR/Cas9 technology and is designed to inactivate the kallikrein B1 (KLKB1) gene, responsible for producing the kallikrein precursor protein. By targeting this gene, NTLA-2002 aims to prevent HAE attacks. The therapy has received multiple regulatory designations, including Orphan Drug and RMAT Designation by the U.S. FDA and Priority Medicines (PRIME) Designation by the European Medicines Agency, underscoring its potential impact.

Hereditary angioedema is characterized by severe, unpredictable inflammatory attacks that can be life-threatening. Affecting approximately one in 50,000 people, HAE currently has no cure, and existing treatments often involve chronic administration that may not fully prevent attacks. Intellia's NTLA-2002 represents a promising advancement in the quest to provide a more effective, one-time treatment option for HAE patients.