Sebelipase alfa

Identification

Name
Sebelipase alfa
Accession Number
DB11563
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
Description

Sebelipase alfa is a recombinant form of the enzyme lysosomal acid lipase (LAL) approved for the treatment of lysosomal acid lipase deficiency (LAL-D). The amino acid sequence for sebelipase alfa is the same as the amino acid sequence for human LAL. Sebelipase alfa is an orphan drug which is expected to cost about $310,000 for annual treatment in the United States. Sebelipase alfa is marketed under the brand name Kanuma™ by Alexion Pharmaceuticals, Inc.

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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
KanumaSolution2 mgIntravenousAlexion Pharma Gmbh2018-04-05Not applicableCanada
KanumaInjection, solution, concentrate2 mg/1mLIntravenousAlexion Pharmaceuticals2015-12-08Not applicableUs
Categories
UNII
K4YTU42T8G
CAS number
1276027-63-4

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.

Associated Conditions
Pharmacodynamics
Not Available
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. 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.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Sebelipase alfa FDA Approval [Link]
External Links
UniProt
P38571
KEGG Drug
D10377
PubChem Substance
347911202
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sebelipase_alfa
ATC Codes
A16AB14 — Sebelipase alfa
AHFS Codes
  • 44:00.00 — Enzymes
FDA label
Download (356 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentCholesterol Ester Storage Disease (CESD) / Lysosomal Acid Lipase Deficiency1
2Active Not RecruitingTreatmentLysosomal Acid Lipase Deficiency1
2CompletedTreatmentCholesterol Ester Storage Disease (CESD) / LAL-Deficiency / Lysosomal Acid Lipase Deficiency1
2, 3Active Not RecruitingTreatmentLysosomal Acid Lipase Deficiency / Wolman's Disease1
2, 3TerminatedTreatmentLysosomal Acid Lipase Deficiency / Wolman's Disease1
3Active Not RecruitingTreatmentCholesterol Ester Storage Disease (CESD) / Lysosomal Acid Lipase Deficiency1
Not AvailableCompletedTreatmentLysosomal Acid Lipase Deficiency1
Not AvailableNo Longer AvailableNot AvailableLysosomal Acid Lipase Deficiency1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solution, concentrateIntravenous2 mg/1mL
SolutionIntravenous2 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Taxonomy

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

Drug created on April 05, 2016 12:57 / Updated on November 14, 2018 12:59