Rare Daily Staff

French biotech Lysogene said that Sarepta terminated their licensing agreement for LYS-SAF302, a phase 2/3 gene therapy for the treatment of mucopolysaccharidosis type IIIA, effective as of July 11, 2022. The termination follows unsuccessful discussions for transferring back to Lysogene the responsibility for the global commercial supply of LYS-SAF302.

With the termination, Lysogene regains development and commercialization rights for LYS-SAF302 in the U.S. and other non-EU territories as well as the responsibility for global commercial supply of LYS-SAF302, all previously granted to Sarepta under the October 2018 agreement. Lysogene will be entitled to receive reimbursement for certain costs associated with the termination.

Mucopolysaccharidosis (MPS IIIA), or Sanfilippo syndrome, is a rare inherited neurodegenerative disease affecting approximately 1 in 100,000 newborns. It is characterized by intractable behavioral problems and developmental regression resulting in early death. It is caused by mutations in the SGSH gene, which encodes an enzyme called Heparan-N-sulfamidase necessary for heparan sulfate (HS) recycling in cells. The disrupted lysosomal degradation and resulting storage of HS and glycolipids such as gangliosides leads to severe neurodegeneration. There are currently no treatment options for patients.

LYS-SAF302 is a second-generation gene therapy designed to deliver a functional copy of the SGSH gene to the brain through a one-time direct-to-central nervous system administration. It was granted Orphan Drug designation in the United States and European Union. In the U.S., it also has obtained Fast Track and Rare Pediatric Disease designations.

In October 2020, Lysogene reported a patient death in the AAVance clinical trial, a global phase 2/3 trial of its gene therapy for MPS IIIA, which had been put on hold a few months before on safety concerns based on observations in some patients of localized findings on MRI images at the intracerebral injection sites that suggested a potential connection to delivery. At the time of the hold, Lysogene said no clinical symptoms had been observed that could be directly attributed to the observed MRI findings.

AAVance is currently fully enrolled and fully dosed, and all patients are being monitored per study protocol. The primary endpoint data readout of this registrational trial is expected mid-2022, as initially anticipated.

“With the data readout expected in a few months’ time, we believe more than ever that LYS-SAF302 is an important treatment option for patients suffering from MPSIIIA, and we remain fully committed to the MPSIIIA community,” said Karen Aiach, chair and CEO of Lysogene.

Lysogene said it remains focused on its strategic objective of becoming a leading gene therapy technological platform targeting CNS diseases. “Our priority remains to execute on our existing pipeline with the completion of the LYS-SAF302 pivotal trial, the respective completion and initiation of the recruitment of the safety and efficacy cohorts of the LYS-GM101 clinical trial for the treatment of GM1 gangliosidosis and to move forward our preclinical programs in Fragile X and Gaucher/Parkinson,” Aiach said.

Photo: Karen Aiach, chair and CEO of Lysogene

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