Genethon and Hansa Biopharma Announce Initiation of a Phase 2 Trial of imlifidase as a Pre-Treatment to GNT-0003 in Severe Crigler-Najjar Syndrome
Hansa Biopharma and Genethon have initiated GNT-018-IDES, a Phase 2 trial evaluating imlifidase as pre-treatment to gene therapy GNT-0003 in patients with Crigler-Najjar syndrome who have pre-existing antibodies against AAV vectors. The trial aims to enable gene therapy treatment for patients previously excluded due to anti-AAV antibodies, which affect up to 1 in 3 potential recipients. The study will include three patients aged ≥18 years requiring phototherapy, with data expected in 2025. GNT-0003 is currently in a pivotal trial and has received EMA PRIME status, potentially becoming the first gene therapy for Crigler-Najjar syndrome.
Hansa Biopharma e Genethon hanno avviato GNT-018-IDES, uno studio di Fase 2 che valuta l'imlifidase come trattamento pre-traslazionale alla terapia genica GNT-0003 in pazienti con sindrome di Crigler-Najjar che hanno anticorpi preesistenti contro i vettori AAV. Lo studio mira a rendere possibile il trattamento con terapia genica per i pazienti precedentemente esclusi a causa degli anticorpi anti-AAV, che colpiscono fino a 1 paziente su 3 potenziali riceventi. Lo studio includerà tre pazienti di età ≥18 anni che necessitano di fototerapia, con dati attesi per il 2025. GNT-0003 è attualmente in uno studio pivotale e ha ricevuto lo stato EMA PRIME, diventando potenzialmente la prima terapia genica per la sindrome di Crigler-Najjar.
Hansa Biopharma y Genethon han iniciado GNT-018-IDES, un estudio de Fase 2 que evalúa imlifidase como tratamiento previo a la terapia génica GNT-0003 en pacientes con síndrome de Crigler-Najjar que tienen anticuerpos preexistentes contra los vectores AAV. El estudio tiene como objetivo habilitar el tratamiento de terapia génica para pacientes que fueron excluidos previamente debido a anticuerpos anti-AAV, lo que afecta hasta a 1 de cada 3 posibles receptores. El estudio incluirá a tres pacientes de ≥18 años que requieren fototerapia, con datos esperados para 2025. GNT-0003 está actualmente en un estudio pivotal y ha recibido el estatus EMA PRIME, convirtiéndose potencialmente en la primera terapia génica para el síndrome de Crigler-Najjar.
한사 바이오파마와 제네톤은 GNT-018-IDES를 시작했습니다. 이는 2상 시험으로서, AAV 벡터에 대한 기존 항체를 가진 크리글러-나자르 증후군 환자들에게 유전자 치료 GNT-0003에 대한 사전 치료제로 이mlifidase를 평가합니다. 이 시험은 AAV 항체로 인해 이전에 배제된 환자들에게 유전자 치료를 가능하게 하는 것을 목표로 하며, 이는 최대 3명의 잠재적인 수령자 중 1명에게 영향을 미칠 수 있습니다. 이 연구는 광치료가 필요한 ≥18세 환자 3명을 포함할 예정이며, 2025년에 데이터가 예상됩니다. GNT-0003은 현재 중요한 시험 중에 있으며 EMA PRIME 지위를 받았으며, 크리글러-나자르 증후군에 대한 첫 번째 유전자 치료제가 될 가능성이 있습니다.
Hansa Biopharma et Genethon ont lancé GNT-018-IDES, un essai de Phase 2 évaluant l'imlifidase comme traitement préliminaire à la thérapie génique GNT-0003 chez des patients atteints du syndrome de Crigler-Najjar ayant des anticorps préexistants contre les vecteurs AAV. L'essai vise à rendre possible le traitement par thérapie génique pour des patients auparavant exclus en raison d'anticorps anti-AAV, ce qui affecte jusqu'à 1 sur 3 des receveurs potentiels. L'étude inclura trois patients âgés de ≥18 ans nécessitant une photothérapie, avec des données attendues en 2025. GNT-0003 est actuellement dans un essai pivot et a reçu le statut EMA PRIME, devenant potentiellement la première thérapie génique pour le syndrome de Crigler-Najjar.
Hansa Biopharma und Genethon haben GNT-018-IDES ins Leben gerufen, eine Phase-2-Studie, die imlifidase als Vorbehandlung für die Gentherapie GNT-0003 bei Patienten mit Crigler-Najjar-Syndrom evaluiert, die über bereits bestehende Antikörper gegen AAV-Vektoren verfügen. Die Studie zielt darauf ab, die Gentherapie für Patienten zu ermöglichen, die zuvor aufgrund von Anti-AAV-Antikörpern ausgeschlossen wurden, die bis zu 1 von 3 potenziellen Empfängern betreffen können. Die Studie umfasst drei Patienten im Alter von ≥18 Jahren, die eine Phototherapie benötigen, und die Daten werden für 2025 erwartet. GNT-0003 befindet sich derzeit in einer entscheidenden Studie und hat den EMA PRIME-Status erhalten und könnte die erste Gentherapie für das Crigler-Najjar-Syndrom werden.
- Second clinical-stage partnership with gene therapy companies
- EMA PRIME status granted for GNT-0003
- Potential to be first gene therapy treatment for Crigler-Najjar syndrome
- Small trial size of only three patients
- Results not expected until 2025
Insights
The initiation of this Phase 2 trial represents a significant development in gene therapy accessibility. The combination of imlifidase with GNT-0003 could potentially solve a critical limitation in AAV-based gene therapies, where up to
The study design, involving three adult patients requiring phototherapy and a three-month observational period, is well-structured to evaluate both safety and efficacy. With Genethon's GNT-0003 already showing promising results in earlier trials and holding EMA's PRIME status, this new approach could significantly expand the eligible patient population for gene therapy treatment.
The expected data readout in 2025 will be important in determining whether this combination approach can effectively overcome the immune response barrier in gene therapy delivery.
This collaboration marks a strategic expansion in Hansa Biopharma's gene therapy enablement program, being the second of three partnerships to reach clinical stage. The potential market impact is substantial, as success could position Hansa's imlifidase as a important pre-treatment for various AAV-based gene therapies. The addressable market could expand significantly by including previously ineligible patients.
The PRIME designation from EMA for GNT-0003 indicates regulatory support and could accelerate the path to market. For Hansa, this represents a valuable opportunity to demonstrate imlifidase's utility beyond its current applications, potentially opening new revenue streams in the growing gene therapy market.
The trial will be conducted in patients with pre-existing anti-AAV antibodies which limit use of gene therapy treatment
Søren Tulstrup, President and CEO, Hansa Biopharma said, “We know that anti-AAV antibodies prevent up to 1 in 3 people from benefitting from gene therapies using AAV-vectors.1-4 That’s why our collaboration with Genethon and the initiation of the Phase 2 clinical trial in Crigler-Najjar syndrome is so important. This collaboration with Genethon is the second of our three partnerships with leading gene therapy companies to have reached the clinical stage, marking an important milestone in our efforts to enable a much larger group of patients to benefit from potentially lifesaving gene therapies.”
Antibodies against AAV vectors remain a major challenge, as their presence in patients excludes them from entering clinical studies with potentially curative gene therapy treatments and from access to currently marketed and future gene therapies.
Frédéric Revah, CEO, Genethon added: "This new clinical trial reflects Genethon’s commitment in pursuing innovative strategies to ensure and broaden access to gene therapies for patients suffering from rare diseases. Patients with pre-existing neutralizing antibodies against AAV vectors cannot today benefit from gene therapy. The initiation of this clinical trial and the collaboration with Hansa Biopharma is a crucial step for Genethon and highlights several years of pioneering research to understand and control the immune response to AAV in order to make gene therapy more effective and to increase the number of patients able to access it."
GNT-018-IDES, sponsored by Genethon, is a single arm Phase 2 trial with a total of three patients aged ≥18 years with Crigler-Najjar syndrome and pre-formed anti-AVV8 antibodies and requiring phototherapy. Once screened, patients will undergo a three-month observational period before being dosed with imlifidase followed by GNT-0003. Genethon and Hansa expect to communicate data from the trial in 2025.
GNT-0003 is currently being evaluated in a pivotal clinical trial following the positive results of the phase 1-2 dose escalation study showing safety and efficacy of GNT-0003, and was granted PRIME priority drug status from the EMA. If successful, GNT-0003 would be the first gene therapy treatment for Crigler-Najjar syndrome.
Notes to editors
About imlifidase
Imlifidase is a unique antibody-cleaving enzyme originating from Streptococcus pyogenes that specifically targets IgG and inhibits IgG-mediated immune response.5 It has a rapid onset of action, cleaving IgG-antibodies and inhibiting their activity within hours after administration. Imlifidase has conditional marketing approval in
About Crigler-Najjar syndrome
Crigler-Najjar syndrome is a rare genetic liver disease characterized by abnormally high levels of bilirubin in the blood (hyperbilirubinemia), which leads to irreversible neurological damage manifested as muscle weakness, lethargy, deafness, mental retardation, and eye movement paralysis. This accumulation of bilirubin is caused by a deficiency of the UGT1A1 enzyme, responsible for transforming bilirubin into a substance that can be eliminated by the body. It can result in significant neurological damage and death if not treated quickly. At present, patients must undergo phototherapy for up to 12 hours a day to keep their bilirubin levels below the toxicity threshold. Crigler-Najjar syndrome is an ultra-rare disease affecting less than one case per one million people per year.6
About imlifidase and gene therapy
Imlifidase is currently being evaluated as a pre-treatment to gene therapy in areas of high unmet need. Many gene therapies are based on the use of Adeno Associated Viruses (AAV) vectors.1-4,7 In some patients the immune system carries antibodies that counteract the gene therapy treatment preventing its success. 1-4,8-10 Pre-treatment with imlifidase prior to AAV-based gene therapy treatment has the potential to inactivate antibodies and thereby enable gene therapy in patients with pre-existing antibodies to AAV-based gene therapies.9 Currently, it is estimated that anti-AAV antibodies on average prevent 1 in 3 people from benefiting from gene therapy treatments.1-4,8
About Hansa Biopharma
Hansa Biopharma is a pioneering commercial-stage biopharmaceutical company on a mission to develop and commercialize innovative, lifesaving and life-altering treatments for patients with rare immunological conditions. Hansa Biopharma has developed a first-in-class immunoglobulin G (IgG) antibody-cleaving enzyme therapy, which has been shown to enable kidney transplantation in highly sensitized patients. Hansa Biopharma has a rich and expanding research and development program based on the Company’s proprietary IgG-cleaving enzyme technology platform, to address serious unmet medical needs in transplantation, autoimmune diseases, gene therapy and cancer. Hansa Biopharma is based in
About Genethon
A pioneer in the discovery and development of gene therapies for rare diseases, Généthon is a non-profit organization created by the AFM-Téléthon. The first gene therapy to treat spinal muscular atrophy, incorporating technologies developed at Genethon, is marketed worldwide. With over 200 scientists and professionals, Genethon pursues its goal of developing innovative therapies that change the lives of patients suffering from rare genetic diseases. Thirteen products from Genethon's R&D or collaborations are in clinical trials for diseases of the liver, blood, immune system, muscles and eyes. A further seven products could enter clinical trials in the next five years. To find out more www.genethon.com
©2024 Hansa Biopharma AB. Hansa Biopharma, the beacon logo, IDEFIRIX, and IDEFIRIX flower logo are trademarks of Hansa Biopharma AB,
References
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Lundstrom K. Viral Vectors in Gene Therapy: Where Do We Stand in 2023? Viruses. 2023 Mar 7;15(3):698. doi: 10.3390/v15030698. PMID: 36992407; PMCID: PMC10059137. |
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Falese L, et al. Strategy to detect pre-existing immunity to AAV gene therapy. Gene Ther. 2017 Dec;24(12):768-778. doi: 10.1038/gt.2017.95. Epub 2017 Nov 6. PMID: 29106404; PMCID: PMC5746592. |
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Leborgne C, et al. IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies. Nat Med. 2020 Jul;26(7):1096-1101. doi: 10.1038/s41591-020-0911-7. Epub 2020 Jun 1. PMID: 32483358. |
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Au H.K, et al. (2022) Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings. Front. Med. 8:809118. doi: 10.3389/fmed.2021.809118 |
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