Clinical: Single CRISPR Infusion Curbs Hereditary Angioedema Attacks

Hereditary angioedema due to C1 inhibitor deficiency causes recurrent, unpredictable and sometimes life-threatening swelling, and existing prophylaxis demands lifelong dosing yet often leaves attacks incompletely controlled. Lonvo-z is designed as a one-time treatment that uses CRISPR-Cas9 gene editing, delivered to the liver via lipid nanoparticles, to permanently inactivate the KLKB1 gene, thereby reducing production of plasma prekallikrein and curbing downstream bradykinin generation and swelling.

In the global, double-blind phase 3 HAELO study, 80 patients aged 16 years or older were randomised 2:1 to a single 50 mg intravenous infusion of lonvo-z or placebo.

From weeks 5 to 28, the mean monthly attack rate fell to 0.26 with lonvo-z versus 2.10 with placebo. Sixty-two per cent of treated patients were attack-free without prophylaxis, against 11% on placebo, and moderate-to-severe attacks dropped by 91%. Total plasma kallikrein declined by roughly 65% within two weeks and remained stable thereafter, while quality-of-life scores improved well beyond the clinically meaningful threshold.

Safety was reassuring. The most common adverse events were mild-to-moderate infusion-related reactions, headache and fatigue. No serious or grade 3 or higher adverse events were reported in the lonvo-z group.

The trial was led by Danny M. Cohn and Padmalal Gurugama at Amsterdam University Medical Center and Cambridge University Hospitals, respectively, and it was published in the New England Journal of Medicine on 12 June 2026. The trial was funded by Intellia Therapeutics and announced in a press release on 13 June 2026.

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