Intellia Therapeutics announced compelling three-year follow-up data from its Phase 1 trial of lonvoguran ziclumeran (lonvo-z), a CRISPR-based gene editing therapy for hereditary angioedema (HAE), showing sustained efficacy that could transform treatment for this rare genetic disorder. The results were presented at the European Academy of Allergy and Clinical Immunology Congress 2025 in Glasgow.
Sustained Clinical Efficacy Across All Patients
The Phase 1 data demonstrated remarkable durability, with a single intravenous dose of lonvo-z achieving a 98% mean reduction in monthly HAE attack rate across all 10 patients over the three-year study period compared to pre-treatment baseline. All patients remained both attack-free and treatment-free for a median of 23 months through the latest follow-up.
"Seeing all 10 patients in the Phase 1 portion of this study free from both HAE attacks and chronic therapy at nearly two years of median follow-up is incredibly encouraging," said John Leonard, M.D., Intellia's President and Chief Executive Officer. "These data fuel our optimism for the outcomes of our ongoing Phase 3 HAELO study, which we expect to report in the first half of 2026."
The study evaluated three dose levels administered via intravenous infusion: 25 mg (N=3), 50 mg (N=4), and 75 mg (N=3). Deep, dose-dependent and durable reductions in plasma kallikrein protein levels continued to be observed through the latest assessment across all patients.
Favorable Safety Profile Maintained
Lonvo-z demonstrated a well-tolerated safety profile consistent with earlier data. The most frequent adverse events were infusion-related reactions (IRRs), which were mostly Grade 1 and resolved with all patients receiving the full dose. Notably, with up to three years of follow-up, no treatment-emergent serious adverse events were observed, and no treatment-related adverse events occurred during the period following 28 days after dosing.
Advancing Toward Regulatory Approval
Intellia's global Phase 3 HAELO trial, evaluating the 50 mg dosage in a randomized, double-blind, placebo-controlled design, has successfully completed screening ahead of schedule. More than half of the screened patients were enrolled from U.S. sites, and the study is no longer recruiting.
The company expects to submit a biologics license application (BLA) in 2026 to support a planned U.S. launch in 2027. Additional data from the Phase 2 portion of the ongoing Phase 1/2 study is planned for presentation in the second half of 2025.
Addressing Unmet Medical Need
"People living with HAE often report a reduced quality of life because they worry about the likelihood of their next attack, either because they still experience attacks or are reminded of it by their use of chronic therapy," explained Dr. Joshua Jacobs, Medical Director at Allergy and Asthma Clinical Research, Inc. "Based on the data, it is reasonable to expect lonvo-z could offer patients the potential to be free from both physical HAE attacks and the burden of managing chronic HAE treatment."
CRISPR Technology Platform
Lonvo-z represents an investigational in vivo CRISPR-based gene editing therapy designed to prevent HAE attacks by inactivating the kallikrein B1 (KLKB1) gene, which encodes for prekallikrein, the kallikrein precursor protein. The therapy has received five notable regulatory designations, including Orphan Drug and RMAT Designation by the FDA, the Innovation Passport by the UK MHRA, Priority Medicines (PRIME) Designation by the European Medicines Agency, and Orphan Drug Designation by the European Commission.
The ongoing Phase 1/2 study evaluates lonvo-z in adults with Type I or Type II hereditary angioedema, with enrollment in both portions now complete. Intellia dosed the first patient in the Phase 3 HAELO trial in January 2025.
