Sarepta and Lysogene Sign Licensing Deal for LYS-SAF302, Potential Gene Therapy for Sanfilippo Type A

Sarepta Therapeutics has signed a licensing agreement with Lysogene for the development of investigational gene therapy LYS-SAF302 to treat mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A, the companies recently announced.

Under the terms of the deal, Sarepta gains exclusive commercial rights to LYS-SAF302 in the United States and all areas outside of Europe, and Lysogene will maintain exclusive commercial rights to the therapy in Europe.

A pivotal Phase 2/3 clinical trial, which will evaluate LYS-SAF302’s ability to improve or stabilize patients’ neurodevelopmental status, is set to begin in the last quarter of 2018. According to the agreement, Lysogene will be in charge of completing the pivotal trial.

Sarepta will also now be responsible for global manufacturing of LYS-SAF302. Previously, Lysogene experienced manufacturing delays, causing the company to push the Phase 2/3 trial to the second half of 2018.

“We stand together today with the MPS community and Lysogene in service of a common goal of developing what could be a transformative therapy for this cruel disease,” Doug Ingram, Sarepta’s president and CEO, said in a press release. “As with our other therapies targeted to serious, life-altering genetic diseases, we share with Lysogene a sense of urgency and a deep commitment to see this program through to fruition. Toward that goal, Sarepta will leverage its expertise in rare disease therapies and gene therapy to bring LYS-SAF302 to the MPS community.”

Sanfilippo syndrome type A is the most prevalent and severe form of the disease, and occurs due to mutations in the SGSH gene, which provides instructions for the production of an enzyme called sulfamidase. This enzyme is responsible for breaking down large sugar molecules called heparan sulfate (HS).

Sulfamidase deficiency causes HS buildup inside lysosomes — the cell compartments responsible for digesting and recycling substances — progressively damaging cells, tissues, and several organs in the body.

LYS-SAF302 is a gene therapy that uses a viral vector — known as the AAVrh10 virus — which has the ability to penetrate into the brain and target the central nervous system. Once there, LYS-SAF302 replaces the mutated SGSH gene with a healthy version of the gene.

This gene therapy is a one-time treatment that allows the body to produce the missing enzyme, which slows or halts disease progression.

A previous proof-of-concept study in MPS IIIA preclinical models showed that LYS-SAF302 led to high expression, wide distribution, and correction of HS breakdown by producing the missing enzyme. LYS-SAF302 use (at all doses tested) did not lead to any unexpected deaths, nor any changes in clinical signs, body weight, behavior, or large-scale changes in the brain.

These positive preclinical studies supported LYS-SAF302’s investigational new drug application to the U.S. Food and Drug Administration — a request for authorization to administer an investigational medicine to humans.

“This partnership with Sarepta, an innovative global leader in genetic diseases, is a major step forward for Lysogene in our commitment to bring a therapy to market to treat MPS IIIA patients,” said Karen Aiach, Lysogene’s CEO and founder.

The agreement also gives Sarepta specific option rights to another, undisclosed central nervous system-associated gene therapy candidate.