NAV

Sebelipase alfa

Identification

Summary

Sebelipase alfais 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
蛋白质的平均重量t
55000.0 Da
Sequences
> Sebelipase阿尔法SGGKLTAVDPETNMN蛋白质序列VSEIISYWGFPSEEYLVETEDGYILCLNRIPHGRKNHSDKGPKPV 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

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Associated Conditions
Contraindications & Blackbox Warnings
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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.2Hypersensitivity 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.2Endogenous 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.2Dyslipidemia 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.2From 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 Cmaxof sebelipase alfa following intravenous administration of 1 mg/kg every other week were 942 ng.hr/mL and 490 ng/mL, respectively.2In patients ≥12 years old, the AUC and Cmaxranged between 1454-1861 ng.hr/mL and 784-957 ng/mL, respectively.2

The approximate Tmaxof 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.2In 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
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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/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug InteractionsLearn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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

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Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image
Kanuma Injection, solution, concentrate 2 mg/ml Intravenous Alexion Europe Sas 2020-12-20 Not applicable EU flag
Kanuma Solution 2 mg / mL Intravenous Alexion Pharma Gmbh 2018-04-05 Not applicable Canada flag
Kanuma Injection, solution, concentrate 2 mg/1mL Intravenous Alexion Pharmaceuticals, Inc. 2015-12-08 Not applicable US flag

Categories

ATC Codes
A16AB14 — Sebelipase alfa
Drug Categories
Chemical TaxonomyProvided byClassyfire
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
  1. Sebelipase alfa FDA Approval [Link]
  2. FDA Approved Drug Products: Kanuma (sebelipase alfa) for intravenous injection [Link]
  3. 产品特点:EMA总结Kanuma (sebelipase alfa) concentrate for solution for intravenous infusion [Link]
UniProt
P38571
KEGG Drug
D10377
PubChem Substance
347911202
RxNav
1726975
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sebelipase_alfa

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
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
2, 3 Terminated Treatment Lysosomal Acid Lipase Deficiency/Wolman's Disease 1
1 Recruiting Treatment Gaucher Disease, Type 3/MPS II/MPS IVA/MPS VI/MPS VII/Myocardial Perfusion Imaging/Pompe Disease (Infantile-Onset)/Type 2 Gaucher Disease/Wolman's Disease 1
1, 2 Completed Treatment Cholesterol Ester Storage Disease (CESD)/LAL-Deficiency/Lysosomal Acid Lipase Deficiency 1
Not Available No Longer Available Not Available Lysosomal Acid Lipase Deficiency 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