CRISPR therapy poised for first FDA approval to edit genes inside the body

Intellia Therapeutics is seeking FDA approval for lonvoguran ziclumeran, or lonvo-z, a CRISPR-Cas9 treatment for hereditary angioedema, a rare disorder that causes painful and sometimes dangerous swelling. Unlike the approved CRISPR therapy Casgevy, which requires doctors to remove a patient’s cells, edit them in a laboratory and reinfuse them after intensive chemotherapy, lonvo-z edits genes inside the body. A single infusion delivers fatty particles carrying instructions for CRISPR components to the liver. There, the treatment disables the gene that produces prekallikrein, a protein that contributes to blood-vessel leakage and swelling attacks. The procedure takes one day, and Intellia says trial data show the treatment remains effective four years later. The FDA is expected to decide on the application by 10 March.

The approach could spare patients the burdens of repeated preventive and emergency medication, as well as the time, cost and chemotherapy associated with cell-based gene editing. Its lasting effect is encouraging, but editing directly in the body creates distinct safety challenges: clinicians cannot screen edited cells beforehand for unintended genetic changes, and treatment may affect other organs or trigger harmful immune reactions. Those concerns are especially salient after a participant in a separate Intellia in-vivo gene-editing study developed liver damage and died; the FDA temporarily halted two studies before lifting the hold with additional safety requirements. Approval would mark the first CRISPR medicine delivered directly into a person’s body.