Antibody-Clearing Enzyme Allows First AAV Gene Therapy Dosing in Previously Ineligible Patient

SEVILLE, SPAIN – October 13, 2025 – A collaboration between French research institute Genethon and Swedish company Hansa Biopharma has achieved a clinical breakthrough, successfully treating a patient with a gene therapy who was previously ineligible due to pre-existing immunity to the viral vector.

Data presented today at the European Society of Gene and Cell Therapy (ESGCT) meeting demonstrated that an enzyme called imlifidase (marketed as Idefirix) can temporarily clear out antibodies, creating a therapeutic window for AAV (adeno-associated virus) gene therapy administration.

Overcoming AAV Immunity in Crigler–Najjar Syndrome
The treatment involved a 22-year-old woman with the ultra-rare liver disorder Crigler–Najjar syndrome (CNS), a condition requiring up to 12 hours of nightly phototherapy to prevent irreversible brain damage. The patient was excluded from the original clinical trial for Genethon’s GNT003 gene therapy because she had pre-existing antibodies to the vector used, AAV8.

The Strategy: The patient received a pretreatment infusion of imlifidase to rapidly and briefly clear the circulating AAV8 antibodies. Two days later, she received Genethon’s gene therapy, which delivers the genetic instructions for the essential bilirubin-metabolizing enzyme.

Initial Efficacy: The treatment appeared to be at least partially effective, as the patient’s bilirubin levels—a key indicator of the disease—dropped within a week of the gene therapy infusion. This is the first time such results have been presented in detail at a major scientific conference.

Durability Question: Bilirubin levels remained lower for about three months while she continued phototherapy. When she discontinued the blue light treatment, however, bilirubin levels returned to baseline, suggesting the gene therapy’s expression may have diminished over time.

“This is the first time we have seen a patient treated with AAV vectors that already had pre-exposure to AAVs,” said Giuseppe Ronzitti, a researcher at Genethon involved in the study.

A Growing Strategy for AAV Gene Therapy
Hansa Biopharma has been actively testing imlifidase as a pretreatment to broaden the eligible patient population for various gene therapies.

Duchenne Muscular Dystrophy (DMD): The data follows an earlier announcement that imlifidase was successfully used to pretreat three boys with DMD who subsequently received Sarepta Therapeutics’ Elevidys gene therapy.

Safety: The imlifidase pretreatment in the CNS patient appeared safe, with the temporary antibody depletion not causing infection. The patient experienced mild to moderate transient elevations in liver enzymes, common side effects after gene therapy infusion.

Future Potential: Researchers are optimistic that this strategy could be expanded to enable redosings of AAV gene therapies, which is currently not possible due to patients developing immunity after the initial treatment. Ongoing testing is planned, with two more CNS patients slated for enrollment.

Rival company Vivet Therapeutics also presented Phase 1 data on its own antibody-clearing drug, VTX-PID, at the conference, showing it could reduce anti-AAV3B antibodies, highlighting the intensifying race to solve the problem of AAV immunity.