Sebelipase Alfa (1 brand name, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION.
Brand Names
- KANUMA
Boxed Warning
Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate KANUMA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue KANUMA and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1)].
Indications and Usage
KANUMA® is indicated for the treatment of patients with a diagnosis of Lysosomal Acid Lipase (LAL) deficiency.
Contraindications
None.
Mechanism of Action
LAL deficiency is an autosomal recessive lysosomal storage disorder characterized by a genetic defect resulting in a marked decrease or loss in activity of the lysosomal acid lipase (LAL) enzyme. The primary site of action of the LAL enzyme is the lysosome, where the enzyme normally causes the breakdown of lipid particles, including LDL-c and triglycerides. Deficient LAL enzyme activity results in progressive complications due to the lysosomal accumulation of cholesteryl esters and triglycerides in multiple organs, including the liver, spleen, intestine, and the walls of blood vessels. The resulting lipid accumulation in the liver may lead to increased liver fat content and progression of liver disease, including fibrosis and cirrhosis. Lipid accumulation in the intestinal wall leads to malabsorption and growth failure. In parallel, dyslipidemia due to impaired degradation of lysosomal lipid is common with elevated LDL-c and triglycerides and low HDL-cholesterol (HDL-c). Sebelipase alfa binds to cell surface receptors via glycans expressed on the protein and is subsequently internalized into lysosomes. Sebelipase alfa catalyzes the lysosomal hydrolysis of cholesteryl esters and triglycerides to free cholesterol, glycerol and free fatty acids.