Kanuma (Sebelipase alfa) in Treatment of Lysosomal Acid Lipase Deficiency

KANUMA (sebelipase alfa) injection, for intravenous use

KANUMA (sebelipase alfa) is a recombinant human lysosomal acid lipase (rhLAL). Lysosomal acid lipase (EC 3.1.1.13) is a lysosomal glycoprotein enzyme that catalyzes the hydrolysis of cholesteryl esters to free cholesterol and fatty acids and the hydrolysis of triglycerides to glycerol and free fatty acids. KANUMA is produced by recombinant DNA technology in the egg white of eggs laid by genetically engineered chickens. Purified sebelipase alfa is a monomeric glycoprotein containing 6 N-linked glycosylation sites and has a molecular mass of approximately 55,000 daltons. The amino acid sequence for sebelipase alfa is the same as the amino acid sequence for human LAL. 


Sebelipase alfa binds to cell surface receptors in the hepatocytes 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.

Initial U.S. Approval: 2015

INDICATIONS AND USAGE
KANUMA™ is a hydrolytic lysosomal cholesteryl ester and triacylglycerol-specific enzyme indicated for the treatment of patients with a diagnosis of Lysosomal Acid Lipase (LAL) deficiency.

DOSAGE AND ADMINISTRATION
Patients with Rapidly Progressive LAL Deficiency Presenting within the First 6 Months of Life: The recommended starting dosage is 1 mg/kg as an intravenous infusion once weekly. For patients who do not achieve an optimal clinical response, increase to 3 mg/kg once weekly.
Pediatric and Adult Patients with LAL Deficiency: The recommended dosage is 1 mg/kg as an intravenous infusion once every other week. 
 Administration Instructions
 Infuse over at least 2 hours. 
Consider further prolonging the infusion time for the 3 mg/kg dose or if a hypersensitivity reaction occurs. 
Consider a 1-hour infusion for the 1 mg/kg dose in patients who tolerate the infusion. 

DOSAGE FORMS AND STRENGTHS
Injection: 20 mg/10 mL (2 mg/mL) solution in single-use vials.

CONTRAINDICATIONS
None.

WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions including Anaphylaxis: Observe patients during and after the infusion. Consider interrupting the infusion or lowering the infusion rate, based on the severity of the reaction. If a severe hypersensitivity reaction occurs, immediately stop the infusion and initiate appropriate treatment. Pre-treatment with antipyretics and/or antihistamines may prevent subsequent reactions in those cases where symptomatic treatment is required. 
Hypersensitivity to Eggs or Egg Products: Consider the risks and benefits of treatment in patients with known systemic hypersensitivity reactions to eggs or egg products. 

ADVERSE REACTIONS
The most common adverse reactions are: • Patients with Rapidly Progressive Disease Presenting within the First 6 Months of Life (≥30%): diarrhea, vomiting, fever, rhinitis, anemia, cough, nasopharyngitis, and urticaria. 
Pediatric and Adult Patients (≥8%): headache, fever, oropharyngeal pain, nasopharyngitis, asthenia, constipation, and nausea. 





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