A Multicenter Study of SBC-102 (Sebelipase Alfa) in Patients With Lysosomal Acid Lipase Deficiency/ ARISE (Acid Lipase Replacement Investigating Safety and Efficacy)

Lysosomal Acid Lipase Deficiency (LALD) is a genetic disease which is characterized by
abnormal lipid accumulation in many parts of the body due to a marked decrease in activity
of the enzyme lysosomal acid lipase (LAL). Although a single disease, LALD presents with two
major forms: early onset and late onset. Early onset LALD, also known as Wolman Disease, is
characterized by severe malabsorption, growth failure, and hepatic failure and is usually
fatal within the first year of life.

The late onset form of the disease, also known as Cholesteryl Ester Storage Disease (CESD),
occurs in both children and adults and is an under-appreciated cause of fatty liver with
prominent microvesicular steatosis and cirrhosis. Although the natural history of the
disease has not been well studied, serious liver complications are frequently described
including early death and liver transplantation. Other complications includes premature
atherosclerosis (hardening of arteries) associated with high levels of total cholesterol and
low-density lipoprotein (LDL) cholesterol, often called the "bad" cholesterol. The levels of
triglycerides can also be high and the levels of high-density lipoprotein (HDL) cholesterol
(the "good" cholesterol) are typically low.

Current treatments mainly focus on control of the lipid abnormalities through diet and the
use of lipid lowering medications. New treatments are needed for patients with LALD as
current treatments only address some aspects of the disease and disease progression to
cirrhosis still occurs. In pre-clinical studies and studies in patients with LALD, treatment
with SBC-102 (sebelipase alfa) has been shown to produce improvements in markers of liver
damage and in the lipid abnormalities. The purpose of this study is to examine the effects
of using SBC-102 to treat late onset LALD (CESD) through a placebo-controlled, randomized,
double-blinded study in both affected children and adults.

Inclusion Criteria:

- Subject and/or subject's parent or legal guardian provides informed consent

- Subject is ≥4 years of age

- Deficiency of LAL enzyme activity confirmed by dried blood spot (DBS) testing at
screening

- ALT ≥1.5x ULN

- Female subjects of childbearing potential must not be pregnant or breastfeeding

- Subjects receiving lipid-lowering therapies must be on a stable dose of the
medication

- Subjects receiving medications for the treatment of non-alcoholic fatty liver disease
must be on a stable dose

Exclusion Criteria:

- Severe hepatic dysfunction (Child-Pugh Class C)

- Other medical conditions or comorbidities which, in the opinion of the Investigator,
would interfere with study compliance or data interpretation

- Previous hematopoietic or liver transplant procedure

- Received treatment with high-dose corticosteroids (acute or chronic) within 26 weeks.
(Note: Subjects receiving maintenance therapy with low-dose oral, intranasal,
topical, or inhaled corticosteroids are considered eligible for the study)

- Known hypersensitivity to eggs

- Participated in a study employing an investigational medicinal product within 4 weeks
prior to randomization