Sebelipase alfa (SBC-102) is an enzyme replacement for Lysosomal Acid Lipase (LAL) Deficiency, a lysosomal storage disorder (LSD). The product is a recombinant form of the human LAL enzyme. This enzyme is responsible for the metabolism of cholesteryl esters and triglycerides that are delivered to lysosomes by a variety of routes including low-density lipoprotein (LDL) receptor mediated endocytosis. Sebelipase alfa contains glycan structures that are specifically recognized and internalized by specific receptors into key target cells. In November 2010, Synageva reported data from preclinical studies at the American Society of Human Genetics demonstrating uptake and localization to lysosomes in vitro in key cell types, including macrophages and fibroblasts. In addition, sebelipase alfa reduced lipid substrate levels in diseased tissues and corrected disease abnormalities associated with deficiency of the LAL enzyme, including growth failure and liver pathology in a disease model of LAL Deficiency.
At the American Association for the Study of Liver Diseases meeting in November 2012, Synageva reported six month data of sebelipase alfa from adult patients with LAL Deficiency who enrolled in a Phase I/II extension study. At six months, sebelipase alfa corrected a broad range of abnormalities associated with LAL Deficiency, including normalization of serum transaminases, which are markers of liver damage, along with decreases in LDL-C and improvements in other lipid abnormalities associated with LAL Deficiency. Improvements in blood disease activity markers with sebelipase alfa were also accompanied by decreases in liver fat content and liver volume as assessed by imaging studies. Sebelipase alfa was well tolerated throughout the initial six months of the extension study. The majority of adverse events were mild and unrelated to sebelipase alfa.
Synageva currently evaluates sebelipase alfa in global clinical trials and sebelipase alfa has been granted orphan designations by the US Food and Drug Administration ("FDA"), the European Medicines Agency, and the Japanese Ministry of Health, Labour and Welfare. Additionally, sebelipase alfa received fast track designation by the FDA, and Breakthrough Therapy designation by the FDA for early onset LAL Deficiency. In addition to clinical studies, we have initiated Natural History Studies in approximately 20 countries.
We are pursuing a broad development strategy that includes clinical trials in patients with both early onset and late onset LAL Deficiency, also known as Wolman disease and Cholesteryl Ester Storage Disease (CESD) respectively. Our program goals, which have been developed in collaboration with the global regulatory authorities, are to assess safety and tolerability in infants, children and adults to demonstrate clinical meaningful effects on the medical complications of LAL Deficiency.
For more information about our clinical programs for sebelipase alfa, please visit clinicaltrials.gov or click here if you would like to contact Synageva regarding LAL Deficiency.
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