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 (HNSA) and Genethon announced the initiation of GNT-018-IDES, a Phase 2 trial combining imlifidase with gene therapy GNT-0003 for Crigler-Najjar syndrome patients with pre-existing anti-AAV antibodies. The trial will evaluate a single intravenous administration of GNT-0003 following imlifidase pre-treatment in three adult patients requiring phototherapy. This collaboration aims to address a significant challenge, as anti-AAV antibodies prevent up to 1 in 3 people from accessing gene therapies. Data from the trial is expected in 2025. GNT-0003 is currently in a pivotal trial and has received EMA PRIME priority status.
Hansa Biopharma (HNSA) e Genethon hanno annunciato l'avvio di GNT-018-IDES, uno studio di Fase 2 che combina imlifidase con la terapia genica GNT-0003 per pazienti affetti da syndrome di Crigler-Najjar con anticorpi anti-AAV preesistenti. Lo studio valuterà una singola somministrazione endovenosa di GNT-0003 dopo un pre-trattamento con imlifidase in tre pazienti adulti che richiedono fototerapia. Questa collaborazione mira a affrontare una sfida significativa, poiché gli anticorpi anti-AAV impediscono a 1 persona su 3 di accedere alle terapie geniche. I dati dello studio sono attesi nel 2025. GNT-0003 è attualmente in uno studio cruciale e ha ricevuto lo status di priorità EMA PRIME.
Hansa Biopharma (HNSA) y Genethon anunciaron el inicio de GNT-018-IDES, un ensayo de Fase 2 que combina imlifidase con la terapia génica GNT-0003 para pacientes con sindrome de Crigler-Najjar que tienen anticuerpos anti-AAV preexistentes. El ensayo evaluará una única administración endovenosa de GNT-0003 tras un pretratamiento con imlifidase en tres pacientes adultos que requieren fototerapia. Esta colaboración tiene como objetivo abordar un desafío significativo, ya que los anticuerpos anti-AAV impiden que hasta 1 de cada 3 personas acceda a terapias génicas. Se esperan datos del ensayo en 2025. GNT-0003 está actualmente en un ensayo pivotal y ha recibido el estatus de prioridad EMA PRIME.
한사 바이오파르마 (HNSA)와 제네톤은 GNT-018-IDES의 개시를 발표했습니다. 이 2상 시험은 기존의 항-AAV 항체가 있는 크리글러-나자르 증후군 환자에게 임리피다제를 유전자 치료제 GNT-0003와 결합하여 시행합니다. 이 시험은 광선 치료가 필요한 3명의 성인 환자에게 임리피다제 사전 치료 후 GNT-0003의 단일 정맥 투여를 평가할 것입니다. 이 협력은 항-AAV 항체가 최대 3명 중 1명이 유전자 치료에 접근하는 것을 방해하는 중요한 문제를 해결하는 것을 목표로 하고 있습니다. 시험 데이터는 2025년에 예상됩니다. GNT-0003은 현재 중요한 임상시험 중이며 EMA PRIME 우선 심사를 받았습니다.
Hansa Biopharma (HNSA) et Genethon ont annoncé le lancement de GNT-018-IDES, un essai de Phase 2 combinant l'imlifidase avec la thérapie génique GNT-0003 pour des patients atteints du syndrome de Crigler-Najjar ayant des anticorps anti-AAV préexistants. L'essai évaluera une administration intraveineuse unique de GNT-0003 après un prétraitement par imlifidase chez trois patients adultes nécessitant une photothérapie. Cette collaboration vise à relever un défi significatif, car les anticorps anti-AAV empêchent jusqu'à 1 personne sur 3 d'accéder aux thérapies géniques. Les données de l'essai sont attendues pour 2025. GNT-0003 est actuellement en phase d'essai crucial et a reçu le statut de priorité EMA PRIME.
Hansa Biopharma (HNSA) und Genethon haben den Beginn von GNT-018-IDES angekündigt, einer Phase 2 Studie, die Imlifidase mit der Gentherapie GNT-0003 für Crigler-Najjar-Syndrom-Patienten mit bestehenden Anti-AAV-Antikörpern kombiniert. Die Studie wird eine einzelne intravenöse Verabreichung von GNT-0003 nach einer vorbehandelnden Imlifidase-Verabreichung bei drei erwachsenen Patienten, die eine Phototherapie benötigen, bewerten. Diese Zusammenarbeit zielt darauf ab, eine bedeutende Herausforderung anzugehen, da Anti-AAV-Antikörper bis zu 1 von 3 Personen daran hindern, Zugang zu Gentherapien zu erhalten. Die Daten aus der Studie werden für 2025 erwartet. GNT-0003 befindet sich derzeit in einer entscheidenden Studie und hat den EMA PRIME-Status erhalten.
- Second clinical-stage partnership for Hansa in gene therapy collaborations
- GNT-0003 has received PRIME priority drug status from EMA
- Previous Phase 1-2 dose escalation study showed safety and efficacy of GNT-0003
- None.
Insights
The initiation of this Phase 2 trial represents a significant milestone in addressing a critical limitation in gene therapy. The collaboration between Hansa and Genethon tackles the important issue of pre-existing AAV antibodies, which currently exclude up to
The trial's design targeting Crigler-Najjar syndrome patients is particularly strategic. By combining imlifidase's IgG-cleaving capability with GNT-0003 gene therapy, this approach could potentially unlock gene therapy access for previously ineligible patients. The PRIME designation from EMA for GNT-0003 adds regulatory validation to this program's potential.
The small trial size of three patients is typical for rare disease studies and with data expected in 2025, this could provide a relatively quick proof-of-concept for this novel combination approach. If successful, this protocol could become a blueprint for expanding gene therapy access across multiple indications.
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.
Contacts for more information:
HANSA BIOPHARMA
Evan Ballantyne, Chief Financial Officer
IR@hansabiopharma.com
Stephanie Kenney, VP Global Corporate Affairs
media@hansabiopharma.com
GENETHON
Stéphanie Bardon
communication@genethon.fr +33 (0) 6.45.15.95.87
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
- Boutin S, et al. Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum Gene Ther. 2010 Jun;21(6):704-12. doi: 10.1089/hum.2009.182. PMID: 20095819.
- Calcedo R, Wilson JM. Humoral Immune Response to AAV. Front Immunol. 2013 Oct 18;4:341. doi: 10.3389/fimmu.2013.00341. PMID: 24151496; PMCID: PMC3799231.
- Veron P, Leborgne C, Monteilhet V, Boutin S, Martin S, Moullier P, Masurier C. Humoral and cellular capsid-specific immune responses to adeno-associated virus type 1 in randomized healthy donors. J Immunol. 2012 Jun 15;188(12):6418-24. doi: 10.4049/jimmunol.1200620. Epub 2012 May 16. PMID: 22593612.
- Kruzik A, et al. Prevalence of Anti-Adeno-Associated Virus Immune Responses in International Cohorts of Healthy Donors. Mol Ther Methods Clin Dev. 2019 Jun 7;14:126-133. doi: 10.1016/j.omtm.2019.05.014. PMID: 31338384; PMCID: PMC6629972.
- European Medicines Agency. Idefirix® summary of product characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/idefirix-epar-product-information_en.pdf.
- https://www.genethon.com/our-pipeline/crigler-najjar-syndrome/. Last accessed: 29 November 2024
- 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.
- 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.
- 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.
- 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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