Intellia Reports Positive Three-Year Follow-up Data from Phase 1 CRISPR Trial in Hereditary Angioedema

Earlier this week, Intellia Therapeutics reported positive long-term durability data from patients with hereditary angioedema (HAE) who received the experimental CRISPR therapy lonvoguran ziclumeran (lonvo-z) in an ongoing Phase 1/2 trial.

In vivo knockout of kallikrein B1 gene to reduce HAE inflammatory attacks

HAE is a rare genetic disease characterised by severe inflammatory attacks with swelling in various organs and tissues. The plasma kallikrein protein is known to drive multiple inflammatory pathways, including the production of the inflammatory mediator bradykinin, which is overproduced in HAE. Current standard of care treatments reduce attack frequency but do not eliminate attacks completely.

Lonvo-z (formerly known as NTLA-2002) is designed to knock out the kallikrein B1 (KLKB1) gene in hepatocytes. This gene encodes prekallikrein, a precursor of plasma kallikrein, thus its knockout permanently reduces plasma kallikrein activity and halts the production of bradykinin to prevent HAE attacks.

The therapy is administered intravenously as a single dose of Cas9 mRNA and KLKB1-targeting gRNA via lipid nanoparticles.

A single dose of lonvo-z eliminated severe HAE attacks with favourable safety profile

The latest data, presented orally at the European Academy of Allergy and Clinical Immunology Congress held June 13-16, 2025 in Glasgow, covers three years of follow-up from the Phase 1 portion of the trial in patients who received a single dose of lonvo-z.

The results show complete freedom from inflammatory attacks after a single dose of lonvo-z across all 10 patients in the study. The data further show that 100% of patients have been attack-free since the last update presented at the European Academy of Allergy and Clinical Immunology Congress in 2024 and summarised in a previous clinical trial update here.

In the Phase 1 portion of the study, a one-time dose of 25 mg (n=3), 50 mg (n=4) or 75 mg (n=3) of lonvo-z was administered via intravenous infusion. Plasma kallikrein protein levels were measured along with HAE attacks. At the February 12 data cutoff, patients were attack-free and treatment-free for a median of 23 months. With up to three years of follow-up, a single dose of lonvo-z led to a mean reduction in monthly HAE attack rate of 98% over the study period, compared to pre-treatment baseline. For all 10 patients, deep, dose-dependent and durable reductions in plasma kallikrein protein continued to be observed through the latest assessment.

Across all three dose levels, lonvo-z has been well tolerated and continues to demonstrate a favourable safety profile consistent with the earlier durability data presented in 2024. The most frequent adverse events observed during the study period were infusion-related reactions that were mostly Grade 1 and resolved with all patients receiving the full dose.

With up to 3 years of follow-up, no treatment-emergent serious adverse events were observed, and no treatment-related adverse events were observed during the period following 28 days after dosing.

Phase 3 HAELO trial ongoing

Intellia's Phase 3 HAELO trial of lonvo-z is currently ongoing. The company is preparing to submit a biologics license application (BLA) in 2026 with a commercial launch planned for 2027. New and longer-term data from the Phase 2 portion of the ongoing Phase 1/2 study is planned to be presented in the second half of 2025.

The sustained three-year data support lonvo-z as a potential functional cure for HAE, offering the possibility of complete elimination of inflammatory attacks after a single treatment.

We will provide further updates on the lonvo-z trials as they emerge.

For a complete overview of CRISPR IND approvals and ongoing gene-editing clinical trials, check out CRISPR Medicine News' Clinical Trials Database.