Researchers at Amsterdam UMC, in collaboration with other hospitals, have successfully completed the first-ever Phase 3 study of in vivo CRISPR therapy. In this large, double-blind Phase 3 trial, 80 patients with hereditary angioedema were randomly assigned to receive either CRISPR therapy or a placebo. CRISPR therapy is a medical technology that allows doctors to precisely correct errors in a cell’s DNA to treat certain genetic diseases. Study leader Danny Kohn is enthusiastic: “This study proves that this treatment is indeed effective and safe. This confirmation is exactly what regulators need to approve the first in vivo CRISPR gene editing therapy to market.”
The findings were presented today at the annual meeting of the European Society of Allergy and Clinical Immunology in Istanbul and simultaneously published in the following journals: New England Medical Journal.
Significant reduction in attacks
This study evaluates a one-time CRISPR treatment for hereditary angioedema, a rare disease characterized by recurrent and potentially dangerous swelling. “This is the first time CRISPR therapy has been applied in vivo in a large, double-blind, international phase 3 study,” explains internist Danny Cohn. “A total of 80 patients were randomized to receive either lombogran diclumeran or a placebo.”
The primary outcome was measured between weeks 5 and 28 after a single intravenous infusion. The results showed that aggressive treatment was highly favorable, with a relative reduction in seizures of 87%. Furthermore, 62% of treated patients were seizure-free even without maintenance therapy, compared with only 11% of those in the placebo group. Key secondary outcomes were also very positive, with an 89% reduction in the need for on-demand treatment, a 91% reduction in moderate-to-severe seizures, and a clearly greater improvement in quality of life scores compared to placebo.
Cohn notes that trial participants tend to take the drug as soon as they see any signs of potential swelling.
Therefore, we cannot be certain whether all reported swelling was an actual attack. We expect the number of completely seizure-free patients to increase as we know that participants received active treatment. This awareness will likely give you the confidence to refrain from on-demand therapy. ”
Danny Cohn, Research Leader
One-time treatment
The impact on patients is significant, suggesting that severe chronic diseases may be managed long-term with a single intervention. Dr. Kohn: “Patients do not require ongoing preventive medication and are spared associated side effects. Additionally, this reduces treatment burden, reduces drug dependence, reduces anxiety about future attacks, and ultimately improves quality of life.”
Paving the way for future gene therapy
In terms of safety, this treatment appears to be well tolerated. The most frequent side effects were mild injection-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 very relevant. Not only effective, but also safe,” Cohn emphasizes. He added that data from 37 participants in phase 1 and 2 trials showed that the treatment remained equally effective and safe four years after administration. “This study opens the door to in vivo CRISPR treatments for patients with other genetic diseases. Gene insertion, deletion, and repair are all possible with CRISPR technology.”
sauce:
Amsterdam University Medical Center
Reference magazines:
Cohn, DM; others. (2026). Lonvoguran Ziclumeran – In Vivo CRISPR Gene Editing in Hereditary Angioedema. New England Medical Journal. DOI: 10.1056/nejmoa2600931. https://www.nejm.org/doi/full/10.1056/NEJMoa2600931
