Hansa Biopharma, an innovative commercial biopharmaceutical entity, together with Genethon, a leader in the sphere of gene therapy for rare genetic disorders, announced the launch of GNT-018-IDES. This is a phase 2 clinical trial aimed at individuals with Crigler-Najjar syndrome who have pre-existing antibodies against adeno-associated virus (AAV) vectors. This study aims to assess the safety and effectiveness of a single intravenous dose of Genethon’s gene treatment, GNT-0003, which is administered following pre-therapy with imlifidase. Imlifidase is a pioneering IgG antibody-cleaving enzyme therapy developed by Hansa, targeting patients with severe Crigler-Najjar syndrome and pre-existing antibodies to AAV serotype 8 (AAV8).
Søren Tulstrup, President and CEO of Hansa Biopharma, stated, “Anti-AAV antibodies impede up to 1 in 3 individuals from accessing AAV-vector-driven gene therapies. Hence, the collaboration with Genethon and first stage of the phase 2 trial for Crigler-Najjar syndrome is vital in tackling this impairment. This partnership with Genethon is the second of our three strategic alliances with eminent gene therapy companies to reach clinical trial status, marking a significant step in extending the benefits of potentially life-saving gene therapies to a broader patient base.”
The presence of antibodies against AAV vectors is a significant barrier since it prevents patient participation in clinical studies involving gene therapies that offer curative potential. This limitation extends to access to current and future gene therapies available in the market.
Genethon’s CEO, Frédéric Revah, highlighted, “The initiation of this new clinical trial underscores Genethon’s dedication to following innovative pathways to expand and enhance the availability of gene therapies for those suffering from rare disorders. Patients with pre-formed neutralizing antibodies against AAV vectors are currently unable to reap the benefits of gene therapy. This trial, in collaboration with Hansa Biopharma, is a pivotal move for Genethon, illustrating many years of research focused on decoding and managing the immune response to AAV, aimed at bolstering the gene therapy’s effectiveness and access.”
The GNT-018-IDES trial, led by Genethon, involves a sole-phase examination where three patients, aged 18 and older, diagnosed with Crigler-Najjar syndrome and bearing AAV8 antibodies, will undergo phototherapy. Post-screening, participants will have a three-month evaluation period before receiving imlifidase followed by GNT-0003. Updates on this trial are expected to be released in 2025.
GNT-0003 is under consideration in a crucial trial after achieving positive outcomes in a prior phase 1-2 dose escalation study in terms of safety and effectiveness, receiving PRIME drug status from the European Medicines Agency (EMA). If brought to fruition successfully, GNT-0003 will stand as the inaugural gene therapy for Crigler-Najjar syndrome.
Imlifidase, an antibody-cleaving enzyme derived from Streptococcus pyogenes, specifically targets IgG, curbing IgG-mediated immune reactions. It becomes effective rapidly, breaking down IgG antibodies and dampening their activities within hours post-administration. It has conditional marketing authorization in Europe, marketed as Idefirix, for desensitization treatment in highly sensitized adult kidney transplant patients.
Crigler-Najjar syndrome is a rare genetic liver condition marked by elevated bilirubin levels, potentially leading to irreversible neurological damage cauterized by muscle weakness, lethargy, hearing impairment, cognitive deficits, and paralysis of eye movement. This bilirubin accumulation arises from a deficiency in the UGT1A1 enzyme, necessary for converting bilirubin into an excretable form. Prompt treatment is critical to prevent significant neurological damage or death. Current treatment requires up to 12 hours of daily phototherapy to sustain bilirubin below harmful levels. This syndrome is extremely rare, with less than one case per million annually.
Imlifidase is presently under study as a pre-treatment for gene therapies across several areas of significant unmet needs. Many gene therapies rely on Adeno-Associated Viruses (AAV) vectors.
In several cases, the immune system’s antibodies can hinder gene therapy, preventing therapeutic success. Administering imlifidase before an AAV-based therapy might neutralize these antibodies, facilitating the gene therapy in patients with pre-existing antibodies to AAV-based treatments. It’s estimated that anti-AAV antibodies prevent approximately 1 in 3 individuals from benefiting from such therapies.
Hansa Biopharma is a trailblazing commercial-stage biopharmaceutical firm committed to introducing innovative treatments for those with rare immunological conditions.
Genethon, a non-profit founded by AFM-Téléthon, remains at the forefront of discovering and developing gene therapies tackling rare diseases.