Genethon and Hansa Biopharma start Phase 2 trial of imlifidase for severe Crigler-Najjar syndrome pre-treatment

Hansa Biopharma and Genethon have announced the commencement of GNT-018-IDES, a Phase 2 clinical trial aimed at evaluating a new gene therapy for patients with Crigler-Najjar syndrome who have pre-existing antibodies against adeno-associated virus (AAV) vectors. This group of patients is typically ineligible for gene therapy treatments due to these antibodies. The trial will assess the safety and efficacy of Genethon's gene therapy GNT-0003 after patients are pre-treated with imlifidase, an antibody-cleaving enzyme therapy developed by Hansa Biopharma.

Søren Tulstrup, President and CEO of Hansa Biopharma, highlighted the collaboration's significance, noting that anti-AAV antibodies prevent a substantial number of patients from benefiting from gene therapies utilizing AAV vectors. He emphasized that this trial marks an important milestone in enabling more patients to access potentially life-saving gene therapies. This partnership with Genethon is the second of three collaborations Hansa has with leading gene therapy companies to reach the clinical trial phase.

Antibodies against AAV vectors represent a significant challenge, excluding many patients from gene therapy clinical trials and marketed treatments. Frédéric Revah, CEO of Genethon, emphasized the company's dedication to expanding access to gene therapies for patients with rare diseases. This new clinical trial is a critical step in overcoming the obstacle of pre-existing neutralizing antibodies, making gene therapy more effective and accessible.

The GNT-018-IDES trial, sponsored by Genethon, is designed as a single-arm Phase 2 trial involving three patients aged 18 years or older with Crigler-Najjar syndrome and pre-existing anti-AAV8 antibodies. These patients require phototherapy and will undergo a three-month observational period before receiving imlifidase followed by GNT-0003. Results from the trial are expected to be communicated in 2025.

GNT-0003 is currently under evaluation in a pivotal clinical trial, following promising results from a phase 1-2 dose escalation study that demonstrated its safety and efficacy. The European Medicines Agency (EMA) has granted GNT-0003 PRIME priority drug status. If successful, GNT-0003 would be the first gene therapy treatment available for Crigler-Najjar syndrome.

Crigler-Najjar syndrome is a rare genetic liver disorder that results in high levels of bilirubin in the blood, leading to severe neurological damage and potentially death if not treated promptly. Patients typically require up to 12 hours of phototherapy daily to manage their bilirubin levels. The disease affects fewer than one in a million people annually.

Imlifidase, developed by Hansa Biopharma, is an antibody-cleaving enzyme derived from Streptococcus pyogenes. It specifically targets immunoglobulin G (IgG) antibodies and inhibits the IgG-mediated immune response. The enzyme works rapidly, cleaving IgG antibodies and inhibiting their activity within hours. Imlifidase has received conditional marketing approval in Europe under the trade name IDEFIRIX® for the desensitization treatment of highly sensitized adult kidney transplant patients with positive crossmatch against an available deceased donor.

Hansa Biopharma, based in Lund, Sweden, is dedicated to developing and commercializing innovative treatments for rare immunological conditions. The company is listed on Nasdaq Stockholm under the ticker HNSA.

Genethon, a non-profit organization established by AFM-Téléthon, focuses on developing gene therapies for rare diseases. With a team of over 200 scientists and professionals, Genethon aims to bring innovative therapies to patients suffering from rare genetic disorders. The organization's research has led to the development of several gene therapy products, some of which are already in clinical trials for various conditions affecting the liver, blood, immune system, muscles, and eyes.

The collaboration between Hansa Biopharma and Genethon represents a significant advancement in the field of gene therapy, offering hope to patients with Crigler-Najjar syndrome and potentially other rare genetic disorders in the future.