Intellia Reports Full Phase 3 HAELO Results for One-Time CRISPR Therapy Lonvo-z

Intellia Therapeutics presented additional results from its Phase 3 HAELO trial of lonvoguran ziclumeran (lonvo-z), a one-time in vivo CRISPR gene-editing candidate for hereditary angioedema (HAE), in a late-breaking oral presentation at the European Academy of Allergy & Clinical Immunology (EAACI) Annual Congress 2026 in Istanbul on June 13, according to the company's release, distributed by GlobeNewswire and read via BioSpace. The results were published at the same time in the New England Journal of Medicine.

The data are company-reported. Intellia had already announced that HAELO met its primary endpoint, with an 87% reduction (p<0.0001) in mean monthly attacks in the lonvo-z arm compared with placebo during the efficacy evaluation period from week 5 to week 28.

Secondary endpoints

The new presentation added the trial's remaining key secondary endpoints, comparing 52 patients on lonvo-z with 28 on placebo:

• The monthly rate of attacks requiring on-demand treatment was 0.19 with lonvo-z versus 1.79 with placebo, an 89% reduction (p<0.0001).
• The monthly rate of moderate or severe attacks was 0.11 versus 1.23, a 91% reduction (p<0.0001).
• The Angioedema Quality of Life (AE-QoL) total score improved by 23.51 points from baseline to week 28 with lonvo-z, against 6.47 points with placebo, a difference of 17.04 points (p<0.0001). A 6-point reduction is considered a clinically important improvement.

A previously reported key secondary endpoint showed that 62% of patients on lonvo-z were free of both attacks and long-term preventive therapy during the six-month evaluation period, compared with 11% on placebo. Intellia said patient-level data showed every patient in the lonvo-z arm had a reduction in attack rate from baseline, and that reductions were seen across all evaluated subgroups.

All reported treatment-emergent adverse events were mild or moderate, and there were no serious adverse events in the lonvo-z arm, the company said. Those more common with lonvo-z than placebo included infusion-related reaction, headache, fatigue, back pain and upper respiratory tract infection.

"These are the first Phase 3 results to deliver on the much-heralded promise of in vivo CRISPR gene editing," said John Leonard, Intellia's president and chief executive officer.

How it works and what comes next

Lonvo-z is designed to permanently lower kallikrein by inactivating the kallikrein B1 (KLKB1) gene in the body with a single dose. Intellia said plasma kallikrein levels fell substantially by the first measurement at day 15, reached a steady state by week 5 and stayed stable through the February 10, 2026 data cutoff. Current HAE preventive treatments can require intravenous or subcutaneous dosing as often as twice a week, or daily oral dosing.

The candidate holds FDA orphan drug and regenerative medicine advanced therapy (RMAT) designations. Intellia began a rolling biologics license application with the FDA in April and said it continues to anticipate approval and a US launch in the first half of 2027.