Identification
- Summary
Sebelipase alfa is a recombinant lysosomal acid lipase used to treat lysosomal acid lipase deficiency.
- Brand Names
- Kanuma
- Generic Name
- Sebelipase alfa
- DrugBank Accession Number
- DB11563
- Background
The lysosomal acid lipase (LAL) enzyme is found in lysosomes and is primarily responsible for the metabolism of lipids, and its absence or deficiency results in the accumulation of lipids in various organs. This lipid accumulation can lead to end-organ damage in the form of liver dysfunction or malabsorption secondary to intestinal dysfunction. In addition, patients with LAL deficiency typically develop dyslipidemia, which itself contributes to a number of adverse cardiovascular outcomes.2
Sebelipase alfa is a recombinant form LAL approved for the treatment of LAL deficiency. It was first approved by both the FDA and EMA in 2015 and is marketed under the brand name Kanuma (Alexion Pharmaceuticals).2,3
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Recombinant Enzymes - Protein Chemical Formula
- C1968H2945N507O551S15
- Protein Average Weight
- 55000.0 Da
- Sequences
> Sebelipase alfa protein sequence SGGKLTAVDPETNMNVSEIISYWGFPSEEYLVETEDGYILCLNRIPHGRKNHSDKGPKPV VFLQHGLLADSSNWVTNLANSSLGFILADAGFDVWMGNSRGNTWSRKHKTLSVSQDEFWA FSYDEMAKYDLPASINFILNKTGQEQVYYVGHSQGTTIGFIAFSQIPELAKRIKMFFALG PVASVAFCTSPMAKLGRLPDHLIKDLFGDKEFLPQSAFLKWLGTHVCTHVILKELCGNLC FLLCGFNERNLNMSRVDVYTTHSPAGTSVQNMLHWSQAVKFQKFQAFDWGSSAKNYFHYN QSYPPTYNVKDMLVPTAVWSGGHDWLADVYDVNILLTQITNLVFHESIPEWEHLDFIWGL DAPWRLYNKIINLMRKYQ
Download FASTA Format- Synonyms
- SBC-102
- Sebelipasa alfa
- Sebelipase alfa
Pharmacology
- Indication
Sebelipase alfa 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.2,3
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Lysosomal acid lipase deficiency •••••••••••• •••••••••• ••••••••• ••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Sebelipase alfa serves as a replacement enzyme for patients deficient in lysosomal acid lipase (LAL) caused by a genetic defect. As it is produced using recombinant DNA technology in the eggs of genetically engineered chickens, it should be used with caution in patients with a known history of egg allergy.2 Hypersensitivity reactions, including anaphylaxis, have also been observed in patients without egg allergy - for this reason, appropriate therapy for the treatment of hypersensitivity reactions should be readily available during its administration.2
- Mechanism of action
Lysosomal acid lipase (LAL) deficiency is an inherited storage disorder caused by a genetic defect that results in a marked decrease or loss in activity of the LAL enzyme.2 Endogenous LAL is found in the lysosome and is responsible for the breakdown of lipids - a deficiency of these enzymes results in the accumulation of cholesteryl esters and triglycerides, which lead to a number of downstream consequences such as progressive liver disease, malabsorption, and growth failure.2 Dyslipidemia associated with LAL deficiency may also result in the typical cardiovascular effects associated with elevated lipid levels.
Sebelipase alfa is a recombinant form of human lysosomal acid lipase (rhLAL) which binds to cell surface receptors via glycans expressed on the protein and is subsequently internalized into lysosomes.2 From within the lysosome, sebelipase alfa catalyzes the lysosomal hydrolysis of cholesteryl esters and triglycerides to free cholesterol, glycerol and free fatty acids.2
- Absorption
In patients 4-11 years old, the AUC and Cmax of sebelipase alfa following intravenous administration of 1 mg/kg every other week were 942 ng.hr/mL and 490 ng/mL, respectively.2 In patients ≥12 years old, the AUC and Cmax ranged between 1454-1861 ng.hr/mL and 784-957 ng/mL, respectively.2
The approximate Tmax of sebelipase alfa was similar across all age groups tested and ranged between 1.1-1.3 hours.2
- Volume of distribution
In patients 4-11 years old, the central volume of distribution was approximately 3.6 L.2 In patients ≥12 years old, the central volume of distribution ranged from approximately 5.3 to 5.4 L.2
- Protein binding
Not Available
- Metabolism
As with other therapeutic proteins, the metabolism of sebelipase alfa likely occurs via catabolism to smaller peptides and amino acids.
- Route of elimination
Not Available
- Half-life
The mean half-life of sebelipase alfa following intravenous administration ranged from 5.4 to 6.6 minutes.2
- Clearance
Across all age groups included in pharmacokinetic testing, the mean clearance of sebelipase alpha following intravenous administration of 1 mg/kg every other week ranged from 31.1 - 38.2 L/h.2
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
There are no data regarding overdose with sebelipase alfa. Patients in clinical trials were exposed to doses as high as 7.5 mg/kg once weekly with no specific adverse effects observed.3
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Kanuma Injection, solution, concentrate 2 mg/1mL Intravenous Alexion Pharmaceuticals, Inc. 2015-12-08 Not applicable US 
Kanuma Injection, solution, concentrate 2 mg/ml Intravenous Alexion Europe Sas 2020-12-20 Not applicable EU 
Kanuma Solution 2 mg / mL Intravenous Alexion Pharma Gmbh 2018-04-05 Not applicable Canada 
Categories
- ATC Codes
- A16AB14 — Sebelipase alfa
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- K4YTU42T8G
- CAS number
- 1276027-63-4
References
- General References
- External Links
- UniProt
- P38571
- KEGG Drug
- D10377
- PubChem Substance
- 347911202
- 1726975
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Sebelipase_alfa
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Lysosomal Acid Lipase Deficiency 1 2 Completed Treatment Cholesterol Ester Storage Disease (CESD) / LAL-Deficiency / Lysosomal Acid Lipase Deficiency 1 2 Completed Treatment Lysosomal Acid Lipase Deficiency 1 2 Terminated Treatment Lysosomal Acid Lipase Deficiency 1 2, 3 Completed Treatment Lysosomal Acid Lipase Deficiency / Wolman's Disease 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution, concentrate Intravenous 2 mg/1mL Injection, solution, concentrate Intravenous 2 MG/ML Solution Intravenous 2 mg / mL Solution, concentrate Intravenous 20 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Drug created at April 05, 2016 18:57 / Updated at July 02, 2022 14:09