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

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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.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
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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/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

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
KanumaInjection, solution, concentrate2 mg/mlIntravenousAlexion Europe Sas2020-12-20Not applicableEU flag
KanumaSolution2 mg / mLIntravenousAlexion Pharma Gmbh2018-04-05Not applicableCanada flag
KanumaInjection, solution, concentrate2 mg/1mLIntravenousAlexion Pharmaceuticals, Inc.2015-12-08Not applicableUS flag

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
  1. Sebelipase alfa FDA Approval [Link]
  2. FDA Approved Drug Products: Kanuma (sebelipase alfa) for intravenous injection [Link]
  3. EMA Summary of Product Characteristics: 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 Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentLysosomal Acid Lipase Deficiency1
2CompletedTreatmentCholesterol Ester Storage Disease (CESD) / LAL-Deficiency / Lysosomal Acid Lipase Deficiency1
2CompletedTreatmentLysosomal Acid Lipase Deficiency1
2TerminatedTreatmentLysosomal Acid Lipase Deficiency1
2, 3CompletedTreatmentLysosomal Acid Lipase Deficiency / Wolman's Disease1
2, 3TerminatedTreatmentLysosomal Acid Lipase Deficiency / Wolman's Disease1
1RecruitingTreatmentGaucher Disease, Type 3 / MPS II / MPS IVA / MPS VI / MPS VII / Myocardial Perfusion Imaging / Pompe Disease (Infantile-Onset) / Type 2 Gaucher Disease / Wolman's Disease1
1, 2CompletedTreatmentCholesterol Ester Storage Disease (CESD) / LAL-Deficiency / Lysosomal 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/ML
Injection, solution, concentrateIntravenous2 mg/1mL
SolutionIntravenous2 mg / mL
Solution, concentrateIntravenous20 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