Sangamo Therapeutics, Inc. . the leader in therapeutic genome editing, announced today that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to SB-318, a genome editing product candidate for the treatment of Mucopolysaccharidosis Type I (MPS I), a rare lysosomal storage disorder. Orphan drug designations are granted to drugs and biologics intended to treat rare diseases. The designation provides incentives to advance development of rare disease drugs and for commercialization of those drugs that progress to approval.
MPS I is caused by mutations in the gene encoding the alpha-L-iduronidase (IDUA) enzyme. Using Sangamo's zinc finger nuclease (ZFN) genome editing technology, SB-318 is designed as a single treatment strategy intended to provide stable, continuous production of the IDUA enzyme for the lifetime of the patient.
In 2017, Sangamo plans to conduct the first ever in vivo genome editing clinical trials including Phase 1/2 studies for three lead programs: SB-318 for the treatment of MPS I; SB-913 for the treatment of MPS II, another rare lysosomal storage disorder; and SB-FIX for the treatment of hemophilia B, a rare blood disease. Data from these studies and from a planned clinical trial for a fourth lead program, SB-525, a gene therapy approach for hemophilia A, are expected in late 2017 or early 2018.
Sangamo's ZFN-mediated in vivo genome editing approach makes use of the albumin gene locus, a highly expressing and liver-specific genomic site that can be edited with ZFNs to accept and express therapeutic genes. The approach is designed to enable the patient's liver to permanently produce circulating therapeutic levels of a corrective protein product. The ability to permanently integrate the therapeutic gene in a highly specific targeted fashion significantly differentiates Sangamo's in vivo genome editing approach from conventional AAV cDNA gene therapy approaches. Ultimately, the target population for these programs will include pediatric patients, and it will be important in this population to be able to produce stable levels of therapeutic protein for the lifetime of the patient. With such a large capacity for protein production (approximately 15g/day of albumin), targeting and co-opting only a very small percentage of the albumin gene's capacity is sufficient to produce the needed replacement protein at therapeutically relevant levels with no significant effect on albumin production.
