Investigational Drug Details
| Drug ID: | D322 |
| Drug Name: | Sebelipase Alfa |
| Synonyms: | SBC-102; SBC-102; Sebelipase alfa |
| Type: | Biological drug |
| DrugBank ID: | DB11563 |
| DrugBank Description: | 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. 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). |
| PubChem ID: | -- |
| CasNo: | 1276027-63-4 |
| Repositioning for NAFLD: | Yes |
| SMILES: | -- |
| InChiKey: | -- |
| Molecular Weight: | -- |
| DrugBank Targets: | -- |
| DrugBank MoA: | 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. 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. 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. From within the lysosome, sebelipase alfa catalyzes the lysosomal hydrolysis of cholesteryl esters and triglycerides to free cholesterol, glycerol and free fatty acids. |
| DrugBank Pharmacology: | 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. 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. |
| DrugBank 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. |
| Targets: | -- |
| Therapeutic Category: | Enzyme replacement therapy |
| Clinical Trial Progress: | Phase 2&3 completed (NCT01371825: Sebelipase alfa markedly improved survival with substantial clinically meaningful improvements in growth and other key disease manifestations in infants with rapidly progressive lysosomal acid lipase deficiency.) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted |
|---|
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A07591 | 32432142 | World J Clin Cases | Cholesteryl ester storage disease of clinical and genetic characterisation: A case report and review of literature. | Details |
| A13754 | 29773783 | Am J Case Rep | Cholesteryl Ester Storage Disease: Fatal Outcome without Causal Therapy in a Female Patient with the Preventable Sequelae of Progressive Liver Disease after Many Years of Mild Symptoms. | Details |
| A14783 | 29234937 | Pathologe | [Lysosomal acid lipase deficiency (LAL-D) : Diagnostic and therapeutic options in an underdiagnosed disease]. | Details |
| A23617 | 23624251 | J Hepatol | Hepatic cholesteryl ester accumulation in lysosomal acid lipase deficiency: non-invasive identification and treatment monitoring by magnetic resonance. | Details |
| A44369 | 28804516 | Therap Adv Gastroenterol | The role of sebelipase alfa in the treatment of lysosomal acid lipase deficiency. | Details |