A Phase 2 clinical trial of NTLA-2002, a gene-editing therapy, has demonstrated promising results in patients with hereditary angioedema (HAE), with a significant reduction in swelling attacks. The study, published in The New England Journal of Medicine, showed that a 50 mg dose of NTLA-2002 led to an 80% reduction in swelling attacks over a 16-week period compared to placebo.
NTLA-2002: A Potential Paradigm Shift in HAE Treatment
Hereditary angioedema is a genetic disorder characterized by the overproduction of bradykinin, leading to swelling attacks. Current treatments often require chronic administration and may not completely eliminate attacks, imposing a significant burden on patients. NTLA-2002, developed by Intellia Therapeutics, aims to address this unmet need by using CRISPR technology to inactivate the gene responsible for producing kallikrein, an enzyme that produces bradykinin. This one-time therapy has the potential to permanently reduce kallikrein levels, thereby preventing swelling attacks.
Phase 2 Trial Results: Significant Reduction in Angioedema Attacks
The Phase 2 trial (NCT05120830) included 27 adults with HAE types 1 or 2. Participants received a single infusion of NTLA-2002 at doses of 25 mg or 50 mg, or a placebo. The results showed that 40% of patients in the 25 mg group and approximately 73% (8 out of 11) in the 50 mg group were completely free from attacks over the 16-week follow-up period. In contrast, none of the patients in the placebo group were attack-free during the same period. According to Intellia, all eight patients in the high-dose group have remained completely free from attacks as of the latest assessment without needing additional treatments.
"These NTLA-2002 Phase 2 data are remarkable, showing this investigational therapy could permanently stop swelling attacks with a single infusion," said Danny Cohn, MD, PhD, lead principal investigator of the Phase 2 study at Amsterdam University Medical Center.
Safety and Tolerability
NTLA-2002 was generally well-tolerated in the study, with no serious side effects reported. The most common adverse events were headache, fatigue, and the common cold.
Mechanism of Action and Biomarker Data
Consistent with the Phase 1 findings, biomarker data from the Phase 2 trial indicated that NTLA-2002 effectively reduced kallikrein levels. Patients receiving the 25 mg dose experienced an average reduction of 55% in kallikrein levels, while those in the 50 mg group showed an 86% reduction.
Ongoing Phase 3 Trial
Bolstered by these positive results, Intellia Therapeutics has initiated a Phase 3 clinical trial (HAELO, NCT06634420) to further evaluate the efficacy and safety of the 50 mg dose of NTLA-2002. This trial is currently recruiting adults with HAE types 1 and 2.
"These positive NTLA-2002 Phase 2 results underscore the tremendous potential of our gene editing therapy to be a functional cure and redefine the treatment paradigm for HAE," said John Leonard, MD, president and CEO of Intellia.
