World First: Intellia's In Vivo CRISPR Drug Lonvo-z Meets All Phase 3 Endpoints in HAELO Trial — 87% Attack Reduction in HAE

Intellia Therapeutics announces topline results from the global Phase 3 HAELO trial of lonvoguran ziclumeran (lonvo-z) in hereditary angioedema (HAE) — the world's first positive Phase 3 dataset for any in vivo CRISPR gene editing therapy. In 80 patients randomized 2:1 (52 lonvo-z, 28 placebo), a single subcutaneous dose of lonvo-z achieved an 87% reduction in HAE attack rate compared to placebo over the 6-month efficacy window. The mean monthly attack rate was 0.26 in the lonvo-z arm versus 2.10 in the placebo arm — more than an 8-fold reduction. Critically, 62% of lonvo-z-treated patients were completely attack-free during the efficacy period, versus only 11% on placebo. All pre-specified primary and key secondary endpoints were met. Safety was favorable: no serious adverse events were observed in the lonvo-z group; the most common side effects were mild infusion-related reactions, headache, and fatigue, all transient. Lonvo-z works by permanently editing the KLKB1 gene in liver cells using a single in vivo LNP-delivered CRISPR-Cas9 system, reducing plasma kallikrein production and thereby preventing the bradykinin-mediated swelling attacks that characterize HAE. A single treatment is intended to produce a permanent reduction in HAE attacks without the need for ongoing prophylaxis. HAE affects approximately 1 in 50,000 people globally — an estimated 6,500 in the US alone. Intellia announced it has initiated a rolling biologics license application (BLA) submission with the FDA and is targeting a potential US launch in the first half of 2027. The milestone establishes in vivo CRISPR gene editing — delivering the editing machinery directly to target tissues inside the body — as a clinically validated therapeutic modality beyond ex vivo cell engineering, which had been the only approved approach through Casgevy.