Intellia Therapeutics has announced the initiation of the Phase 3 HAELO clinical trial for NTLA-2002, a CRISPR-based gene-editing therapy designed as a single-dose treatment for hereditary angioedema (HAE). The first patient has been dosed in this pivotal study, marking a significant step toward a potential functional cure for this rare and debilitating genetic disease.
The HAELO trial (NCT06634420) is a global, randomized, double-blind, placebo-controlled study set to evaluate the efficacy and safety of NTLA-2002 in 60 adult participants diagnosed with Type I or Type II HAE. Participants will be randomized in a 2:1 ratio to receive either a single 50mg infusion of NTLA-2002 or a placebo. Patients randomized to the placebo arm will be eligible for optional crossover to NTLA-2002 at week 28. The primary endpoint is the change in the number of HAE attacks from week 5 through week 28.
NTLA-2002: A Novel CRISPR-Based Therapy
NTLA-2002 leverages CRISPR/Cas9 technology to inactivate the KLKB1 gene, which encodes for prekallikrein, a precursor to kallikrein. By reducing kallikrein production, the therapy aims to decrease bradykinin levels, thereby preventing the swelling attacks characteristic of HAE. NTLA-2002 has received several regulatory designations, including Orphan Drug and RMAT Designation by the U.S. Food and Drug Administration (FDA), the Innovation Passport by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA), Priority Medicines (PRIME) Designation by the European Medicines Agency, as well as Orphan Drug Designation by the European Commission.
Promising Phase 1/2 Data
Intellia is initiating the Phase 3 study based on positive safety and efficacy data from the ongoing Phase 1/2 study (NCT05120830) of NTLA-2002. Interim Phase 1 clinical data showed dramatic reductions in attack rate, as well as consistent, deep and durable reductions in kallikrein levels. Data from the phase 1/2 study were recently reported at the 2024 American College of Allergy, Asthma & Immunology Scientific Meeting, held October 24 to 28, in Boston, Massachusetts. Participants in the trial received either a single dose of 25 mg of NTLA-2002, a single dose of 50 mg of NTLA-2002, or a placebo. As of the April 4, 2024, data cutoff, monthly HAE attacks for patients who received the 50 mg dose were reduced by 77% in comparison to the placebo group for weeks 1 to 16 posttreatment and by 81% during weeks 5 to 16 posttreatment. Notably, 8 of the 11 patients who received the pivotal 50 mg dose of NTLA-2002 were completely free of HAE attacks during the 16 week observation period and beyond, with a median follow-up time of 8 months. Furthermore, these 8 patients did not need any additional treatment during this period.
Addressing Unmet Needs in HAE Treatment
HAE is a rare genetic disease affecting approximately 1 in 50,000 people, characterized by severe, recurring, and unpredictable inflammatory attacks. Current treatments often involve lifelong therapies requiring chronic intravenous or subcutaneous administration, or daily oral medication, to manage symptoms. Despite these options, breakthrough attacks can still occur, highlighting the need for more effective and convenient treatments.
Anticipated Timeline and Regulatory Milestones
Intellia anticipates that enrollment in the HAELO study will be completed in the second half of 2025. The company plans to submit a biologics license application (BLA) to the FDA in 2026, with a potential U.S. launch of NTLA-2002 in 2027, pending regulatory approval. These steps underscore Intellia's commitment to addressing the unmet needs of individuals living with HAE.
Expert Commentary
“Initiation of the HAELO Phase 3 trial is a significant milestone for Intellia as we enter the final stage of clinical development for NTLA-2002 for people living with hereditary angioedema,” said Intellia President and Chief Executive Officer John Leonard, M.D. “Data from the ongoing Phase 1/2 study showed great promise that a single-dose treatment can lead to a complete response – no more attacks and no further treatment required. We are working urgently to bring forward NTLA-2002 to address the real-world needs of people suffering from this disease and, ultimately, believe it will bring significant value to patients, physicians and payors.”
