One-Time CRISPR Editing Injection Cuts Hereditary Angioedema Attacks by 87%: Phase 3

Hereditary angioedema (HAE) is a rare genetic disease in which a deficiency of C1 inhibitor causes repeated swelling of the face, limbs, airway and other areas. Swelling of the airway can be life-threatening, so patients have had to receive preventive medicine regularly. The HAELO phase 3 trial, published in The New England Journal of Medicine (NEJM), showed the potential to change this way of treating the disease.

Editing liver cell genes inside the body

Lonvoguran ziclumeran (lonvo-z) is an in vivo editing therapy that delivers the CRISPR-Cas9 editing tool intravenously to inactivate a target gene in liver cells. It blocks production of the substance that causes swelling upstream, and it is being developed by Intellia Therapeutics in the United States.

In the double-blind trial, 80 patients aged 16 or older with C1 inhibitor deficiency were assigned 2:1, and 52 received a single intravenous infusion of lonvo-z 50 mg and 28 received placebo. The primary endpoint was the investigator-confirmed monthly attack rate from week 5 to week 28 after infusion. The result was 0.26 attacks per month in the lonvo-z group and 2.10 in the placebo group, a relative reduction of 87% (95% confidence interval -93 to -78%, P<0.001). As of February 2026, the median follow-up was 7.5 months. Adverse events were reported in 92% of the lonvo-z group and 86% of the placebo group, and those more common in the lonvo-z group were infusion-related reactions, headache, fatigue, back pain and upper respiratory tract infection. There were no serious adverse events or grade 3 or higher adverse events in the lonvo-z group.

Significance and limits

This is a rare case in which in vivo CRISPR editing has shown efficacy in a randomized controlled phase 3 trial. However, follow-up of less than a year is short, so the durability of the effect and long-term safety, especially off-target editing, need to be watched further. Gene editing cannot be reversed, the trial had only 80 people, and it was sponsored by the drug maker, and these points should also be taken into account. The drug is still at the clinical stage before approval.