PracticeUpdate Conference Series_WORLDSymposium 2019

" The interim results provide preliminary evidence that in vivo genome editing occurred and that genome-edited liver cells are able to generate active iduronate-2-sulfatase enzyme in patients with mucopolysaccharidosis II. "

with MPS II who underwent bone marrow transplan- tation. They employed the Hunter Outcome Survey, a global observational registry initiated in 2005 that collects real-world data on the natural history of MPS II and long-term treatment with enzyme replacement therapy with idursulfase. Patients receiving other forms of pharmacological enzyme replacement therapy are excluded from the Hunter Outcome Survey but individuals who have received a bone marrow transplant may be enrolled. In total, 22 patients (61.1%) were European and 14 (38.9%) were North American. A total of 27 patients (75%) were followed pro- spectively in the Hunter Outcome Survey and 9 (25%) were enrolled after their death (followed retrospectively). Median (10th percentile, 90th percentile) ages at symptom onset, diagnosis, and last visit were 0.8 (0.1, 3.0) years (n=26); 2.5 (0.8, 5.0) years (n=35); and 15.2 (4.9, 28.4) years (n=27), respectively. Patients were age 2.6 (0.7, 4.5) years at bone marrow transplantation (n=10). Overall, 14 patients (38.9%) had received at least one idursulfase infu- sion and 16 (44.4%) had not received the infusion. Idursulfase treatment status was unknown in 6 patients (16.7%). Of 7 patients with data available on the relative timing of idursulfase treatment and bone marrow transplantation, 6 patients had started idursulfase before bone marrow transplan- tation and one had started it afterward. Median duration between idursulfase start and bone marrow transplantation was 3.5 (−173.5, 24.3) months (n=7). Cognitive impairment at any time was reported for 21 patients (58.3%, n=36). In total, 13 of 36 patients died. Median age at death was 8.8 (3.4, 17.6) years. The most common cause of death was graft vs host disease/transplant complications (n=4) followed by respiratory failure (n=3). Dr. Muenzer concluded that these long-term data from the Hunter Outcome Survey provide valuable information on patients with MPS II who undergo bone marrow transplantation.

SB-913 is delivered via adeno-associated vector 2/6 vectors. The precision and specificity of SB-913 allows for integration at a targeted genomic loca- tion and is intended to reduce glycosaminoglycan accumulation with lifelong continuous endogenous production of iduronate-2-sulfatase. Dr. Muenzer said to the Global Genes Rare Daily , “The interim results provide preliminary evidence that in vivo genome editing occurred and that genome-edited liver cells are able to generate active iduronate-2-sulfatase enzyme in patients with mucopolysaccharidosis II.” He continued, “More data are needed to understand whether the small increases in idu- ronate-2-sulfatase enzyme activity observed can translate into improved outcomes in patients with mucopolysaccharidosis II treated with this frst generation of SB-913. I look forward to reviewing additional data later this year from the fve patients who have received the high dose of SB-913.” In a related study, Dr. Muenzer and colleagues examined the characteristics of 36 male patients

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WORLDSymposium 2019 • PRACTICEUPDATE CONFERENCE SERIES 19