In vivo CRISPR therapy successfully reduces hereditary angioedema attacks in first Phase III trial

by Amsterdam University Medical Centers

edited by Sadie Harley, reviewed by Robert Egan

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Researchers from Amsterdam UMC, in collaboration with other hospitals, have successfully completed the first Phase III study of an in vivo CRISPR therapy. In this large-scale, double-blind trial, 80 patients with hereditary angioedema were randomized to receive either the CRISPR therapy or a placebo. CRISPR therapy is a medical technique that allows doctors to precisely modify errors in cellular DNA to treat specific hereditary diseases.

Danny Cohn, leader of the research, is highly enthusiastic, saying, "The study demonstrates that the therapy is genuinely effective and safe. This confirmation is exactly what regulatory authorities need to approve the first in vivo CRISPR gene-editing treatment for the market."

The findings were presented at the annual congress of the European Academy of Allergy and Clinical Immunology in Istanbul and simultaneously published in The New England Journal of Medicine.

Significant reduction in attacks

The study evaluates a one-time CRISPR treatment for hereditary angioedema, a rare disorder characterized by recurrent and potentially dangerous swelling. Internist Danny Cohn explains, "This is the first time CRISPR therapy has been applied in vivo within a large, double-blind, international Phase III trial. A total of 80 patients were randomized to receive either lonvoguran-ziclumeran or a placebo."

The primary outcome was measured between weeks 5 and 28 following a single intravenous infusion. The results heavily favored the active treatment, showing an 87% relative reduction in attacks. Furthermore, 62% of treated patients remained attack-free without any maintenance therapy, compared with just 11% in the placebo group.

Key secondary outcomes were also strongly positive: the need for on-demand treatment fell by 89%, moderate-to-severe attacks decreased by 91%, and quality-of-life scores showed a distinctly greater improvement compared with the placebo.

Cohn notes that trial participants tended to take medication at the earliest sign of a potential swelling. "Consequently, we cannot be certain whether all reported swellings were actual attacks," Cohn says.

"We anticipate that the number of completely attack-free patients will rise now that participants know they received the active treatment. This awareness will likely give them the confidence to forgo on-demand therapy."

A single, one-time treatment

The implications for patients are profound, suggesting that a severe, chronic condition can potentially be managed long term with a single intervention.

Cohn said, "Patients may no longer need continuous preventive medication, sparing them the associated side effects. Furthermore, this can alleviate treatment burden, reduce drug dependency, lessen the anxiety of future attacks and ultimately improve quality of life."

Paving the way for future genetic therapies

In terms of safety, the treatment appears to be well tolerated. The most frequent side effects were mild infusion-related reactions, headache, fatigue and back pain, all of which resolved quickly. No serious adverse events were reported in the treatment group.

"This makes the results exceptionally relevant; it is not just effective, it is safe," Cohn emphasizes. He adds that data from 37 participants from the Phase I and II trials show the treatment remains just as effective and safe four years after administration.

"This study opens doors to in vivo CRISPR treatments for patients with other hereditary disorders. Inserting, deleting or repairing a gene—it is all possible with CRISPR technology."

Publication details

Danny M. Cohn et al, Lonvoguran Ziclumeran — In Vivo CRISPR Gene Editing in Hereditary Angioedema, New England Journal of Medicine (2026). DOI: 10.1056/nejmoa2600931

Journal information: New England Journal of Medicine

Key medical concepts

Hereditary angioedemaInfusions, Intravenous

Clinical categories

Allergy and immunology Provided by Amsterdam University Medical Centers Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

Citation: In vivo CRISPR therapy successfully reduces hereditary angioedema attacks in first Phase III trial (2026, June 15) retrieved 15 June 2026 from https://medicalxpress.com/news/2026-06-vivo-crispr-therapy-successfully-hereditary.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.