A single-dose gene editing therapy for a rare genetic condition that causes severe, unpredictable swelling attacks has moved a step closer to becoming the first treatment of its kind to be approved inside the body. The experimental therapy, which uses CRISPR technology to edit genes directly within a patient’s cells, has shown strong results in a late-stage clinical trial and has entered a rolling review process with U.S. regulators.
Intellia Therapeutics reported that its therapy, lonvoguran ziclumeran (lonvo-z), reduced swelling attacks by 87 percent compared with a placebo in a Phase 3 trial involving 80 adults with hereditary angioedema. The condition, which affects about one in 50,000 people, causes sudden episodes of swelling in the hands, feet, face, throat and abdomen that can be painful and, in cases involving the airway, life-threatening. Current treatments require chronic medication to manage symptoms, but many patients still experience breakthrough attacks.
Unlike the only approved CRISPR therapy, Casgevy, which edits cells outside the body before reinfusing them, lonvo-z is delivered as a one-time intravenous infusion. The therapy targets liver cells directly, using CRISPR/Cas9 to disable a gene involved in producing a protein that triggers swelling. In the trial, side effects were mostly mild or moderate, including infusion reactions, headache and fatigue. “The results we are seeing from lonvo-z demonstrate its potential to eliminate the need for chronic medication and related challenges,” said Professor Aleena Banerji, the trial’s principal investigator.
Intellia has begun a rolling submission of its Biologics License Application to the U.S. Food and Drug Administration, a step-by-step process that allows the agency to review sections as they are completed. If approved, the company expects to launch lonvo-z commercially in the first half of 2027. “Lonvo-z will become the world’s first in vivo CRISPR-based gene editing therapy,” said Dr. John Leonard, president and chief executive of Intellia.
The advancement marks a significant milestone for in vivo gene editing, which has long been seen as a more direct and potentially simpler approach than editing cells outside the body. For patients with hereditary angioedema, the prospect of a single-dose cure could mean freedom from daily medications and the constant fear of sudden attacks. Researchers say the therapy’s success could also pave the way for similar CRISPR-based treatments for other genetic disorders in the years ahead.