Intellia Therapeutics Reports Positive Long-Term Data from Phase 1 Study of NTLA-2002 for Hereditary Angioedema

Intellia Therapeutics, Inc., a clinical-stage genome editing company, has announced promising long-term data from the Phase 1 trial of NTLA-2002, a CRISPR-based gene editing therapy aimed at treating hereditary angioedema (HAE). Hereditary angioedema is a rare genetic disorder that causes severe and unpredictable swelling attacks. The findings were presented at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2024 in Valencia, Spain.

NTLA-2002 has shown potential to be a functional cure for HAE, following more than two years of observation. Eight out of ten patients remained attack-free throughout the 16-week primary observation period and during the subsequent follow-up. On average, the therapy led to a 98% reduction in monthly HAE attack rates over more than 20 months of follow-up. Additionally, all patients who discontinued their prophylactic treatments after receiving NTLA-2002 remained free from chronic prophylaxis.

John Leonard, M.D., President and CEO of Intellia, expressed optimism about the results, stating that NTLA-2002 could be a groundbreaking treatment for HAE. Leonard highlighted the durability of the therapy, noting that the majority of patients have been attack-free for over 18 months, even those with severe symptoms. The therapy also demonstrated a favorable safety profile across all dose levels.

In the Phase 1 study, three different doses of NTLA-2002 (25 mg, 50 mg, and 75 mg) were administered intravenously to ten patients. The primary assessment of HAE attack rates occurred after 16 weeks, with ongoing evaluations for up to two years. Across all doses, a robust and sustained reduction in HAE attacks was observed. The longest attack-free interval for an individual patient exceeded 26 months. The two patients with the highest baseline attack rates were attack-free by the end of the primary observation period and remained so through the latest follow-up.

The therapy also led to significant reductions in plasma kallikrein protein levels. Mean reductions were 60% for the 25 mg dose, 88% for the 50 mg dose, and 95% for the 75 mg dose. The most common adverse events were mild, including infusion-related reactions and fatigue, which resolved within two days. No serious or dose-limiting toxicities were observed.

Following the success of the Phase 1 study, Intellia completed enrollment for the Phase 2 randomized, placebo-controlled study, which is further evaluating the 25 mg and 50 mg doses. Topline results from this study are expected mid-year, with detailed data to be presented at a medical meeting later in 2024. The company plans to initiate a pivotal Phase 3 trial in the second half of 2024, pending regulatory feedback.

NTLA-2002 is based on CRISPR/Cas9 technology and has received several regulatory designations, including Orphan Drug and RMAT Designation by the FDA, and PRIME Designation by the European Medicines Agency. The therapy works by inactivating the kallikrein B1 (KLKB1) gene, which is responsible for producing the kallikrein protein that triggers HAE attacks.

Hereditary angioedema affects about one in 50,000 people and is characterized by severe, recurrent swelling attacks. Current treatments for HAE often require chronic administration and may still result in breakthrough attacks. NTLA-2002 aims to offer a one-time treatment option that could significantly improve the quality of life for those affected by HAE.

Intellia Therapeutics continues to lead in the development of CRISPR-based therapies, leveraging its extensive expertise and robust intellectual property portfolio. The company's in vivo programs aim to directly edit disease-causing genes within specific target tissues, while its ex vivo programs focus on engineering human cells to treat various conditions, including cancer and autoimmune diseases.