The European Commission officially announced full approval for the world’s first lentiviral vector-based gene therapy for the treatment of metachromatic leukodystrophy (MLD), a rare neurodegenerative disease of genetic origin: Libmeldy, the result of a collaboration between Telethon Foundation, San Raffaele Hospital and Orchard Therapeutics. This new gene therapy is the outcome of a process that began more than 15 years ago at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) in Milan, where the rationale for this cutting-edge treatment was demonstrated at a preclinical and then clinical level.
“The EC approval of Libmeldy comes more than a decade after the first patient was treated in clinical trials performed at our Institute, and ushers in a remarkable and long-awaited shift in the treatment landscape for eligible MLD patients” said professor Luigi Naldini, director of the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. “Our team at SR-Tiget has been instrumental in advancing the discovery and early-stage research of this potentially transformative therapy to clinical trials supporting its registration over more than 15 years of studies supported by Fondazione Telethon and Ospedale San Raffaele,and we are extremely proud of this achievement and what it means for patients and the field of HSC gene therapy.”
MLD is a very rare, fatal genetic disorder caused by mutations in the ARSA gene which lead to neurological damage and developmental regression. In its most severe and common forms, young children rapidly lose the ability to walk, talk and interact with the world around them, and most pass away before adolescence. Libmeldy is designed as a one-time therapy that aims to correct the underlying genetic cause of MLD, offering eligible young patients the potential for long-term positive effects on cognitive development and maintenance of motor function at ages at which untreated patients show severe motor and cognitive impairments. Eligible patients are represented by children with i) late infantile or early juvenile forms without clinical manifestations of the disease, or with ii) early juvenile form with early clinical manifestations of the disease who still have the ability to walk independently and before the onset of cognitive decline.
With Libmeldy, a patient’s own hematopoietic stem cells (HSCs) are selected, and functional copies of the ARSA gene are inserted into the genome of the HSCs using a self-inactivating (SIN) lentiviral vector before these genetically modified cells are infused back into the patient. The ability of the gene-corrected HSCs to migrate across the blood-brain barrier into the brain, engraft, and express the functional enzyme has the potential to persistently correct the underlying disease with a single treatment.
Libmeldy’s marketing authorisation is valid in all 27 EU Member States, as well as the UK, Iceland, Liechtenstein and Norway. Orchard plans to qualify and work with treatment centers in the EU with experience in HSC transplantation and expertise in MLD to administer Libmeldy.
Libmeldy will also be available in a cryo-preserved formulation: this procedure involves freezing the patient’s cells once they have been engineered with the viral vector and therefore allows to carried out the correction in a different location from the patient. This means that pharmaceutical companies able to carry out the genetic modification will be able to send the drug to clinical centres far away in the world, thus increasing access to the therapy.
In addition, cryopreservation allows quality and safety tests to be carried out, the results of which would not be available in the limited time frame in which fresh cells have to be administered.
This gene therapy is also being tested in the United States, but has not yet been approved by the Food and Drug Administration (FDA).