PracticeUpdate Conference Series_WORLDSymposium 2019

Gene Therapy Using SB-913 Shown to Be Safe and Well Tolerated in MPS II The trial was the first to attempt in vivo genome editing in humans.

T he gene therapy SB-913 has been shown to be well tolerated in mucopolysaccharidosis (MPS) II and further development may proceed. This outcome of the ongoing multicenter, open- label phase I/II dose escalation CHAMPIONS trial was reported at the WORLDSymposium 2019. Joseph Muenzer, MD, of the University of North Carolina in Chapel Hill, North Carolina, and col- leagues wanted to determine whether dose escalation of SB-913 is safe and tolerable in patients with MPS II. The trial is the frst to attempt in vivo genome editing in humans. In CHAMPIONS, a single peripheral intravenous infusion of SB-913 is followed by 3 years of obser- vation. A total of 6 adult subjects with attenuated MPS II have received SB-913. Two subjects partic- ipate in each of three dose cohorts (5e12 vector genomes [vg], 1e13 vg, and 5e13 vg per kilogram of body weight). After up to 10 months of exposure, infusions have been well tolerated and no serious adverse events related to study drug have been reported

at any dose. No persistent transaminitis has been observed. Dr. Muenzer explained that MPS II (Hunter syn- drome) is a rare, progressive, X-linked genetic disorder caused by mutations in the human IDS gene. MPS II is characterized by deficient activity of the lysosomal enzyme iduronate-2-sulfatase. Without functional iduronate-2-sulfatase activity, the glycosaminoglycans dermatan sulfate and heparan sulfate accumulate in the body, leading to widespread tissue and organ damage. Patients with MPS II develop progressive respira- tory and cardiac disease, skeletal abnormalities, and in the severe form, cognitive decline and early death, despite treatment with enzyme replacement therapy. SB-913 is a new type of investigational treatment for MPS II. SB-913 employs zinc-finger nuclease-me- diated in vivo genome editing to insert a normal copy of the IDS transgene into liver cells.

PRACTICEUPDATE CONFERENCE SERIES • WORLDSymposium 2019 18