• The preliminary results are from the ASPIRO open label trial conducted by Astellas Pharma with a gene therapy designed and developed preclinically by Genethon
• After gene therapy treatment, 16 of the 24 children can breathe without assistance, 20 can sit up, 12 can stand and 8 can walk without support (see video of one patient’s progress - https://www.youtube.com/watch?v=F4niMKa0vtI)
• The trial has been paused to investigate severe side effects which caused the death of four children

Genethon, a unique non-profit gene therapy R&D organization founded by the French Muscular Dystrophy Association (AFM-Telethon), today announced The Lancet Neurology published online preliminary results of a clinical trial conducted by Astellas Pharma using a gene therapy developed by Genethon for X-linked myotubular myopathy, a rare genetic muscle disease affecting 1 in 50,000 newborn boys.

Myotubular myopathy is caused by mutations in the MTM1 gene encoding myotubularin, a protein involved in muscle cell function. Characterized by extreme muscle weakness and severe respiratory distress, 50% of affected children die before age 18 months and 75% die before age 10. The gene therapy uses an adeno-associated viral vector (AAV8) to deliver a copy of the MTM1 gene.

Of 24 children enrolled in the ASPIRO trial, conducted in France, Germany, Canada and the U.S., 16 of them can now breathe without assistance, 12 stand up on their own, and 8 can walk. The trial has been paused for an investigation into the origins of the complications responsible for the deaths of 4 children, who showed signs of pre-exiting hepatobiliary pathology.

“These clinical results show both how spectacularly effective gene therapy can be, and the challenges that remain, particularly in terms of side effects in certain contexts,” said Frederic Revah, Genethon CEO. “While our teams are already committed to understanding and anticipating these issues, the knowledge gained from this clinical trial, which highlights certain limitations and particular hepatic susceptibilities, is rich in lessons for the entire scientific community.”

Ana Buj-Bello, Director of Research at Inserm and head of Genethon’s Neuromuscular Diseases and Gene Therapy team, designed the gene therapy. She is one of the authors on The Lancet Neurology article and co-authored the preclinical work that led to the ASPIRO trial.

Dr. Buj-Bello remarked, “I've devoted my entire career working on myotubular myopathy. It took years of research to imagine, design and demonstrate the efficacy of the gene therapy for this very severe and complex disease. Even though we absolutely must understand the reasons for the adverse effects observed in this clinical trial, it is exceptional to see children who were known to be doomed make incredible progress thanks to this drug candidate.” See the video of one patient’s progress in France. This patient was treated at I-Motion, the Institute of Myology’s French pediatric clinical trials center: https://www.youtube.com/watch?v=F4niMKa0vtI

Genethon entered an agreement with Audentes Therapeutics in 2014 for the preclinical development of the gene therapy. Astellas acquired the gene therapy in 2019 with the company’s acquisition of Audentes.

About Genethon

As a pioneer in the discovery and development of gene therapies for rare diseases, Généthon is a non-profit laboratory that was established by AFM-Telethon. A first gene therapy for spinal muscular atrophy to which Généthon contributed has obtained a product license. With more than 200 scientists and professional staff, Genethon is pursuing its aim to develop therapies which change the lives of patients suffering from rare genetic diseases. Thirteen products developed by Genethon are in clinical trial for diseases of the liver, blood, immune system, muscles and eyes. Seven other products could enter clinical trials over the next five years. More information at www.genethon.fr.

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