Approach to management of cross-reactive immunologic material (CRIM)-negative infantile pompe patients treated with ERT: Role of immune modulation in changing the natural history

phenotypes. Early onset (Wolman disease) is characterized by malabsorption, rapidly progressive liver disease, and growth failure with early mortality. Late onset (cholesteryl ester storage disease) is an underappreciated cause of cirrhosis, liver failure and dyslipidemia. We reported previously that four, once-weekly infusions of 0.35, 1 and 3 mg/kg of SBC-102 (rhLAL) were well-tolerated in adults with late onset disease. This report summarizes data from 7 patients who have been dosed for an additional 24 weeks and who are currently receiving every other week (q2w) infusions (1 and 3 mg/kg). Long term treatment with q2w doses of SBC-102 has achieved sustainable reductions in transaminases with a 54% and 30% mean decrease from the original baseline in ALT and AST, respectively, at 24 weeks, with normalization in all subjects. Additionally, long term dosing is associated with improvements in the dyslipidemia associated with LAL deficiency with a 43% and 22% mean reduction in LDL-cholesterol and triglyceride, respectively, and a 14% mean increase in HDL-cholesterol from the original baseline. With the exception of mild, infrequent infusion-related reactions, SBC-102 is well-tolerated through 24 weeks. One patient experienced acute cholecystitis, a serious adverse event deemed unlikely related to SBC-102. These data demonstrate safety and clinical activity of SBC-102 long-term dosing in patients with late onset LAL deficiency.