| Clinical data | |
|---|---|
| Trade names | Eperzan (Europe), Tanzeum (US) |
| Other names | GSK-716155 |
| AHFS/Drugs.com | tanzeum |
| Routes of administration | Subcutaneous (SC) |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Protein binding | Probably none |
| Metabolism | Most likelyproteolysis |
| Eliminationhalf-life | 5 (4–7) days |
| Identifiers | |
| CAS Number | |
| PubChem SID | |
| DrugBank | |
| ChemSpider |
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| UNII | |
| KEGG | |
| Chemical and physical data | |
| Formula | C3232H5032N864O979S41 |
| Molar mass | 72971.34 g·mol−1 |
Albiglutide (trade namesEperzan in Europe andTanzeum in the US) is aglucagon-like peptide-1 agonist (GLP-1 agonist)drug marketed byGlaxoSmithKline (GSK) for treatment oftype 2 diabetes.As of 2017 it is unclear if it affects a person's risk of death.[2] In 2017 GSK announced Albiglutide's withdrawal from the worldwide market for economic reasons, and remaining stocks in the supply chain were effectively depleted by 2018.
Albiglutide was used for the treatment of type 2 diabetes in adults. It can be used alone (ifmetformin therapy is ineffective or not tolerated) or in combination with otherantidiabetic drugs, includinginsulins.[3]
According to a 2015 analysis, albiglutide is less effective than other GLP-1 agonists for loweringglycated hemoglobin (HbA1c, an indicator for long-term blood glucose control) and weight loss. It also seems to have fewer side effects than most other drugs of this class, except for reactions at the injection site which are more common under albiglutide than, for example, underliraglutide.[4]
The US approval lists the thyroidC cell cancersmedullary thyroid carcinoma (MTC) andmultiple endocrine neoplasia type 2 (MEN 2) as contraindications because other GLP-1 agonists are known to cause such cancers in rodents. Albiglutide causesimmunogenicity in rodents, so its cancer risk could not be assessed.[5] The European approval mentions the uncertainty about C cell cancers, but not as a contraindication.[3]
Common side effects (in more than 10% of patients) in clinical trials were diarrhoea,nausea,hypoglycaemia and reactions at the injection site.Upper respiratory tract infections were also common, but only slightly more so than underplacebo. Uncommon but potentially severe side effects included acutepancreatitis (in 0.3% of patients) andhypersensitivity reactions (in fewer than 0.1%).[3][5]
No clinically relevant interactions have been found in studies with a number of drugs that are known for their interaction potential (simvastatin,warfarin,digoxin, andoral contraceptives). Nonetheless, since albiglutide slowsgastric emptying, it could conceivably increase absorption of other drugs if taken at the same time.[3][5]
Albiglutide acts as anagonist at theGLP-1 receptor, which makes it a type ofincretin mimetic. This causes an increase of insulin secretion, predominantly in the presence of highblood glucose, and also slows down gastric emptying.[3]
Unlike other GLP-1 agonists, due to its structure it has difficulty in crossing theblood-brain barrier. This means that it does not affect thecentral nervous system as much as other GLP-1 agonists and may be responsible for the limited weight loss seen in the drug.[6]
Followingsubcutaneous injection, albiglutide reaches highest blood concentrations after three to five days. Steady-state concentrations are achieved after three to five weeks. The substance is most likely broken down byprotease enzymes to smallpeptides andamino acids.[3] Being resistant todipeptidyl peptidase-4 (DPP-4),[5] the enzyme that breaks down GLP-1, albiglutide has abiological half-life of five (four to seven) days, which is considerably longer than the older GLP-1 analogsexenatide and liraglutide.[7][8] This allows for a once-weekly administration,[3] unlike liraglutide but like the extended-release form of exenatide.
Albiglutide is a peptide consisting of 645proteinogenic amino acids with 17disulfide bridges. Amino acids 1–30 and 31–60 constitute two copies of modified human GLP-1, thealanine at position 2 having been exchanged for aglycine for better DPP-4 resistance.[5] The remaining sequence is humanalbumin. The complete sequence is
HGEGTFTSDV SSYLEGQAAK EFIAWLVKGR HGEGTFTSDV SSYLEGQAAK EFIAWLVKGR (2 copies of modified GLP-1, modifications underlined)DAHKSEVAHR FKDLGEENFK ALVLIAFAQY LQQCPFEDHV KLVNEVTEFA KTCVADESAE (albumin starts at the beginning of this line)NCDKSLHTLF GDKLCTVATL RETYGEMADC CAKQEPERNE CFLQHKDDNP NLPRLVRPEVDVMCTAFHDN EETFLKKYLY EIARRHPYFY APELLFFAKR YKAAFTECCQ AADKAACLLPKLDELRDEGK ASSAKQRLKC ASLQKFGERA FKAWAVARLS QRFPKAEFAE VSKLVTDLTKVHTECCHGDL LECADDRADL AKYICENQDS ISSKLKECCE KPLLEKSHCI AEVENDEMPADLPSLAADFV ESKDVCKNYA EAKDVFLGMF LYEYARRHPD YSVVLLLRLA KTYETTLEKCCAAADPHECY AKVFDEFKPL VEEPQNLIKQ NCELFEQLGE YKFQNALLVR YTKKVPQVSTPTLVEVSRNL GKVGSKCCKH PEAKRMPCAE DYLSVVLNQL CVLHEKTPVS DRVTKCCTESLVNRRPCFSA LEVDETYVPK EFNAETFTFH ADICTLSEKE RQIKKQTALV ELVKHKPKATKEQLKAVMDD FAAFVEKCCK ADDKETCFAE EGKKLVAASQ AALGL
with disulfide bridges linking amino acids 113-122, 135-151, 150-161, 184-229, 228-237, 260-306, 305-313, 325-339, 338-349, 376-421, 420-429, 452-498, 497-508, 521-537, 536-547, 574-619, 618-627.[3][9]
It isbioengineered in the yeastSaccharomyces cerevisiae usingrecombinant DNA technology.[3]
The drug was invented byHuman Genome Sciences and was developed in collaboration with GSK.[10]
GSK filed forUS FDA approval on 14 January 2013 and forEuropean Medicines Agency (EMA) approval on 7 March 2013.In March 2014, GSK received approval from theEuropean Commission to market albiglutide under the nameEperzan.[11]In April 2014, the US FDA approved albiglutide under the nameTanzeum.[12]
In August 2017, GSK announced that it intended to withdraw the drug from the worldwide market by July 2018 for economic reasons.[13]