Information about Sebelipase alfa
Lysosomal acid lipase deficiency is an inherited condition which underlies Wolman disease and cholesteryl ester storage disease. The current standard treatment for these two conditions is enzyme replacement therapy using infusions of recombinant forms of lysosomal acid lipase.
Liver safety of Sebelipase alfa
Enzyme replacement therapy is generally well tolerated and has not been linked to serum enzyme elevations or to instances of clinically apparent acute liver injury.
Mechanism of action of Sebelipase alfa
Sebelipase (se" be lye' pase) alfa is a recombinant form of the lysosomal enzyme that is absent or deficient in inherited conditions that are marked by dyslipidemia, early onset of atherosclerosis and fatty liver disease that can progress to cirrhosis. The severe form of lysosomal acid lipase deficiency is known as Wolman disease in which the enzyme is entirely absent. Wolman disease is a severe, progressive disease of infancy marked by severe diarrhea, failure to thrive and progressive hepatic fibrosis and cirrhosis, usually leading to death within the first year of life. The same enzyme defect also appears to be responsible for the milder form of dyslipidemia and liver disease known as cholesterol ester storage disease in which the enzyme is deficient, but not totally absent. Cholesterol ester storage disease typically presents in adolescence or young adulthood, but may go undetected and present with middle age with wide spread complications of atherosclerosis or cirrhosis of unknown cause. The enzyme acts in lysosomes upon cholesterol esters and its deficiency results in accumulation of the cholesterol esters and triglycerides in hepatocytes and diffusely in macrophages in the liver, spleen, adrenals, bone marrow, lymph nodes and intestinal villi. Liver histology demonstrates microvesicular steatosis, foamy macrophages and progressive fibrosis. Serum aminotransferase levels are typically mildly or moderately elevated. Cholesterol lowering agents have been used in an attempt to treat these conditions, but have little effect. Cirrhosis and end stage liver disease can be managed successfully with liver transplantation, and hematopoietic cell transplantation has been reported to reverse some of the manifestations. Recently, infusions of recombinant lysosomal acid lipase have been found to decrease serum enzyme elevations and result in resolution of hepatomegaly in patients with cholesterol ester storage disease. In some cases, the beneficial effects were dramatic with evidence of disease regression. Pilot studies in children with Wolman disease have also had promising results with enzyme replacement.
FDA approval information for Sebelipase alfa
Sebelipase alfa, a recombinant lysosomal acid lipase product extracted from the egg whites laid by transgenic hens, was approved for use in lysosomal acid lipase deficiency in 2015.
Dosage and administration for Sebelipase alfa
The recombinant protein is available in solution in single use vials of 2 mg/mL under the brand name Kanuma. The recommended regimen of therapy varies by indication, but is in the range of 1 to 3 mg/kg infused intravenously every 1 to 2 weeks.
Side effects of Sebelipase alfa
Side effects are few but can include infusion reactions and hypersensitivity.
genetic disorder agents
- gaucher disease agents
glucosylceramide synthase inhibitors (substrate restriction therapy)
lysosomal acid lipase deficiency agents
- agalsidase beta, alglucosidase alfa, alpha1-proteinase inhibitor, elosulfase alfa, galsulfase, idursulfase, laronidase, pegademase
Huntington disease agents
Urea Cycle Disorder Agents