Imlifidase as pretreatment in gene therapy for patients
with Crigler–Najjar syndrome who are immune to AAV
On October 10, 2025, Genethon, a worldwide pioneer and leader in research and development of gene therapy for rare genetic diseases, and Hansa Biopharma, a Sweden-based leader in IgG cleaving enzyme technology announced that a patient with a rare liver disease and immunity to the AAV vector has been successfully treated with Genethon’s AAV-based GNT0003 gene therapy for Crigler-Najjar syndrome, following prior administration of imlifidase, an enzyme capable of temporarily inhibiting the immune response. This encouraging result, achieved in a clinical trial, is a significant advance in the treatment of patients with immunity to AAVs who were previously ineligible for clinical trials and existing gene therapy treatments.
Gene therapy involves injecting a gene drug into an organism using a vector such as AAVs which are commonly used for gene therapy in for example neuromuscular, liver, and eye diseases. Initial contact with the natural virus can cause the body to develop IgG antibodies that neutralize AAVs. It is estimated that one in three people is naturally immune to AAVs, thereby excluding a large number of patients from the possibility of benefiting from gene therapy using an AAV vector. To evaluate potential options for treating patients with natural immunity to AAVs, researchers at Genethon tested imlifidase, an enzyme developed by Hansa Biopharma, as a pre-treatment. This enzyme is capable of cleaving IgG, thereby rapidly and significantly reducing the level of anti-AAV antibodies and allowing the administration of a gene therapy drug candidate.
Dr. Jérémy Do Cao (Béclère Hospital, AP-HP, France) presented at the 2025 congress of the European Society of Gene & Cell Therapy (ESGCT), the results of using imlifidase as a pre-treatment for GNT0003 gene therapy in a patient with a severe form of Crigler–Najjar syndrome who is naturally immune to the AAV8 vector, as part of the clinical trial (GNT-018-IDES) conducted by Genethon in collaboration with Hansa Biopharma. In this first patient treated, the study demonstrated:
• the feasibility and safety of this approach: imlifidase administered prior to GNT0003 gene therapy successfully cleaved and inactivated the patient’s antibodies and enabled treatment with GNT0003. No severe side effects related to GNT0003 or imlifidase were reported.
• initial efficacy data: GNT0003, Genethon’s gene therapy drug candidate significantly lowered the patient’s bilirubin levels, enabling her to stop hours of daily phototherapy, which had been essential to her survival until then. The phototherapy has been interrupted sixteen weeks after the injection, as planned in the protocol. Additional data will be needed to confirm this efficacy in the longer term.
This is the first time that gene therapy has been successfully administered to a patient with Crigler–Najjar syndrome who has antibodies against AAV8. If the results are confirmed in the next stages of the trial, this approach could become a promising option for patients with antibodies to AAVs, who are currently ineligible for clinical trials and existing gene therapy treatments.
10/10/2025
Imlifidase as pretreatment in gene therapy for patients with Crigler–Najjar syndrome who are immune to AAV
Imlifidase as pretreatment in gene therapy for patients
with Crigler–Najjar syndrome who are immune to AAV
On October 10, 2025, Genethon, a worldwide pioneer and leader in research and development of gene therapy for rare genetic diseases, and Hansa Biopharma, a Sweden-based leader in IgG cleaving enzyme technology announced that a patient with a rare liver disease and immunity to the AAV vector has been successfully treated with Genethon’s AAV-based GNT0003 gene therapy for Crigler-Najjar syndrome, following prior administration of imlifidase, an enzyme capable of temporarily inhibiting the immune response. This encouraging result, achieved in a clinical trial, is a significant advance in the treatment of patients with immunity to AAVs who were previously ineligible for clinical trials and existing gene therapy treatments.
Gene therapy involves injecting a gene drug into an organism using a vector such as AAVs which are commonly used for gene therapy in for example neuromuscular, liver, and eye diseases. Initial contact with the natural virus can cause the body to develop IgG antibodies that neutralize AAVs. It is estimated that one in three people is naturally immune to AAVs, thereby excluding a large number of patients from the possibility of benefiting from gene therapy using an AAV vector. To evaluate potential options for treating patients with natural immunity to AAVs, researchers at Genethon tested imlifidase, an enzyme developed by Hansa Biopharma, as a pre-treatment. This enzyme is capable of cleaving IgG, thereby rapidly and significantly reducing the level of anti-AAV antibodies and allowing the administration of a gene therapy drug candidate.
Dr. Jérémy Do Cao (Béclère Hospital, AP-HP, France) presented at the 2025 congress of the European Society of Gene & Cell Therapy (ESGCT), the results of using imlifidase as a pre-treatment for GNT0003 gene therapy in a patient with a severe form of Crigler–Najjar syndrome who is naturally immune to the AAV8 vector, as part of the clinical trial (GNT-018-IDES) conducted by Genethon in collaboration with Hansa Biopharma. In this first patient treated, the study demonstrated:
• the feasibility and safety of this approach: imlifidase administered prior to GNT0003 gene therapy successfully cleaved and inactivated the patient’s antibodies and enabled treatment with GNT0003. No severe side effects related to GNT0003 or imlifidase were reported.
• initial efficacy data: GNT0003, Genethon’s gene therapy drug candidate significantly lowered the patient’s bilirubin levels, enabling her to stop hours of daily phototherapy, which had been essential to her survival until then. The phototherapy has been interrupted sixteen weeks after the injection, as planned in the protocol. Additional data will be needed to confirm this efficacy in the longer term.
This is the first time that gene therapy has been successfully administered to a patient with Crigler–Najjar syndrome who has antibodies against AAV8. If the results are confirmed in the next stages of the trial, this approach could become a promising option for patients with antibodies to AAVs, who are currently ineligible for clinical trials and existing gene therapy treatments.
10/10/2025
On October 10, 2025, Genethon, a worldwide pioneer and leader in research and development of gene therapy for rare genetic diseases, and Hansa Biopharma, a Sweden-based leader in IgG cleaving enzyme technology announced that a patient with a rare liver disease and immunity to the AAV vector has been successfully treated with Genethon’s AAV-based GNT0003 gene therapy for Crigler-Najjar syndrome, following prior administration of imlifidase, an enzyme capable of temporarily inhibiting the immune response. This encouraging result, achieved in a clinical trial, is a significant advance in the treatment of patients with immunity to AAVs who were previously ineligible for clinical trials and existing gene therapy treatments.
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