Lysogene receives FDA fast track designation for LYS-SAF302 gene therapy in MPS IIIA

LYS-SAF302, a second-generation gene therapy, is designed to deliver a functional copy of the SGSH (N-sulfoglucosamine sulfohydrolase) gene to the brain through a one-time direct-to-CNS administration, and is being investigated in the international Phase 2/3 clinical trial AAVance (NCT03612869).

Karen Aiach, Founder and Chief Executive Officer said: “MPS IIIA is a lethal neurological disease with debilitating symptoms for which there is currently no treatment. The FDA’s recognition of LYS-SAF302’s potential to improve neurocognitive deficits in children with MPS IIIA represents an important achievement for Lysogene and the patient community.” Karen Aiach added: “We are also pleased to announce the treatment of the 17th patient with LYS-SAF302, which once again demonstrates our capacity to execute with quality and speed. LYS-SAF302 is the flagship of our differentiated direct-to-CNS gene therapy platform, which has been validated not only by our partner Sarepta, but also by the scientific community. We are fully dedicated to continue the full speed development of LYS-SAF302, as well as all the other programs in our pipeline.”

The Fast Track program facilitates the development and accelerates the review of new drugs for serious conditions, which have the potential to address unmet medical needs. The purpose is to expedite the availability of new treatment options for patients. A product that receives Fast Track designation is eligible for more frequent interactions with FDA, potential eligibility for accelerated approval, priority review, and rolling Biologics License Application (BLA) review.

“This Fast Track designation demonstrates the regulators’ sustained interest in Lysogene’s cutting edge in vivo gene therapy program. LYS-SAF302 has previously received Orphan Drug Designations for the treatment of MPS IIIA in the European Union in 2014 and in the US in 2015, as well as Rare Pediatric Disease Designation in the US,” added Marie Deneux, Chief Regulatory Officer. “In the complex field of gene therapy for neurodegenerative diseases, a continued communication with FDA is essential.”

The AAVance Phase 2/3 clinical study is designed as an open-label, single-arm, multicenter study of LYS-SAF302 for the treatment of MPS IIIA. The study will include 20 patients with the severe classical form of MPS IIIA and has been extensively discussed upfront with key opinion leaders, regulators and health technology assessment bodies, as well as with patient representatives.

As of today, 17 patients have been treated out of the total of 20. The primary objective is to assess the drug efficacy in improving the neurodevelopmental status of patients after 24 months, compared to the expected evolution based on natural history data. Safety, tolerability, effect on behavior, sleep and quality of life will also be collected as secondary endpoints. Lysogene has also set up the sub study, PROVide, collecting supportive video outcomes in the home environment.

MPS IIIA is a rare inherited neurodegenerative lysosomal storage disorder affecting approximately 1 in 100,000 newborns. Inherited in an autosomal recessive pattern, 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 an AAV-mediated gene therapy, the goal of which is to replace the faulty SGSH gene with a healthy copy of the gene. LYS-SAF302 employs the AAVrh10 virus, chosen for its ability to target the central nervous system. Proof-of-concept was established in MPS IIIA pre-clinical models demonstrating strong expression, broad distribution, and the ability of the product to correct lysosomal storage defects by producing the missing enzyme.

Safety data from an IND-enabling toxicity and a biodistribution GLP study showed that, at any dose level evaluated, LYS-SAF302 was not associated with unexpected mortality, change in clinical signs, body weight, behavior or macroscopic findings in the brain. Sarepta holds exclusive commercial rights to LYS-SAF302 in the United States and markets outside Europe; and Lysogene maintains commercial exclusivity of LYS-SAF302 in Europe.

Source: Company Press Release