One-time CRISPR therapy cuts hereditary angioedema attacks in trial
An 80-patient Phase III study found lonvoguran ziclumeran reduced attacks by 87% versus placebo, Amsterdam UMC researchers reported.
By Tom Brennan · Health & Medicine Correspondent
3 min read
A single intravenous CRISPR treatment sharply reduced attacks in people with hereditary angioedema in a Phase III trial, according to Amsterdam UMC researchers. The result could support regulatory review of what the researchers describe as the first in vivo CRISPR gene-editing treatment tested in a large, double-blind Phase III study.
The findings were presented at the annual congress of the European Academy of Allergy and Clinical Immunology in Istanbul and published at the same time in The New England Journal of Medicine. The study tested lonvoguran ziclumeran, a one-time treatment for hereditary angioedema, a rare inherited disorder that can cause repeated and potentially dangerous swelling episodes.
Amsterdam UMC said researchers working with other hospitals enrolled 80 patients and randomly assigned them to receive either the CRISPR therapy or a placebo. The treatment was given as a single intravenous infusion, and the main outcome was assessed from week 5 through week 28 after dosing.
According to the researchers, patients who received lonvoguran ziclumeran had an 87% relative reduction in attacks compared with the placebo group. Amsterdam UMC said 62% of treated patients had no attacks and did not need maintenance therapy during the measured period, compared with 11% of patients who received placebo.
The study also reported lower use of rescue treatment after the CRISPR therapy. Amsterdam UMC said the need for on-demand medication fell by 89%, moderate-to-severe attacks declined by 91%, and quality-of-life scores improved more in the treatment group than in the placebo group.
Researchers point to trial design and safety data
Danny Cohn, the Amsterdam UMC internist who led the research, said the trial showed the treatment was effective and safe. He said those findings are the type of evidence regulators need when considering approval of an in vivo CRISPR treatment.
Cohn also cautioned that trial participants often took on-demand medication at the first sign of possible swelling. Because of that, he said, researchers cannot be certain that every reported swelling episode was a confirmed hereditary angioedema attack.
Amsterdam UMC said the treatment was generally well tolerated. The most common side effects were mild infusion-related reactions, headache, fatigue and back pain, and the university said they resolved quickly. No serious adverse events were reported in the treatment group, according to Amsterdam UMC.
Cohn said longer follow-up from 37 participants in earlier Phase I and II studies showed the treatment remained effective and safe four years after it was given. The Phase III report in The New England Journal of Medicine lists Danny M. Cohn and colleagues as authors of the paper, titled “Lonvoguran Ziclumeran — In Vivo CRISPR Gene Editing in Hereditary Angioedema.”
Potential shift in long-term care
Amsterdam UMC said CRISPR technology allows clinicians to make precise changes in cellular DNA to treat specific inherited diseases. In this case, the therapy is designed as an in vivo treatment, meaning the editing occurs inside the body after administration.
Cohn said a one-time treatment could reduce patients’ reliance on continuous preventive medication and lessen side effects, treatment burden and fear of future attacks. He also said the study could help advance in vivo CRISPR approaches for other hereditary disorders involving gene insertion, deletion or repair.
This story draws on original reporting from Medical Xpress.