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ACETATE CAS NO 141732-76-5
Exenatide, derived from a compound found in the saliva of the Gila monster, a large lizard native to the southwestern US, is a functional analog of Glucagon-Like Peptide-1 (GLP-1), a naturally occuring peptide.
Exenatide (INN, marketed as Byetta, Bydureon) is a glucagon-like peptide-1 agonist(GLP-1 agonist) medication approved in April 2005 for the treatment of diabetes mellitus type 2. It belongs to the group of incretin mimetics and is manufactured by Amylin Pharmaceuticals. Exenatide in its Byetta form is administered as a subcutaneous injection (under the skin) of the abdomen, thigh, or arm, any time within the 60 minutes before the first and last meal of the day. A once-weekly injection has been approved as of January 27, 2012 under the trademark Bydureon
Exenatide is a synthetic version of exendin-4, a hormone found in the saliva of the Gila monster that was first isolated by Dr. John Eng in 1992 while working at the Veterans Administration Medical Center in the Bronx, New York. It displays biological properties similar to human glucagon-like peptide-1 (GLP-1), a regulator of glucose metabolism andinsulin secretion. According to the package insert, exenatide enhances glucose-dependent insulin secretion by the pancreatic beta-cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying, although the mechanism of action is still under study.
Exenatide is a 39-amino-acid peptide, an insulin secretagogue, with glucoregulatory effects. Exenatide was approved by the FDA on April 28, 2005 for patients whose diabetes was not well-controlled on other oral medication. The medication is injected subcutaneously twice per day using a filled pen-like device. The abdomen is a common injection site, after the area is cleaned with an alcohol pad. A new pen must first be tested to see if the medicine is flowing.
|Indication||Indicated as adjunctive therapy to improve glycemic control in patients with Type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of both, but have not achieved adequate glycemic control.|
|Pharmacodynamics||Exenatide is an incretin mimetic, which has glucoregulatory effects. While it is has blood-sugar lowering actions alone, it can also be combined with other medications such as pioglitazone, metformin, sulfonylureas, and/or insulin to improve glucose control. The approved use of exenatide is with either sulfonylureas, metformin and thiazolinediones. The medication is injected twice per day using a pre-filled pen device. Typical human responses to exenatide plus eating include improvements in the initial rapid release of endogenous insulin, suppression of glucagon release by the pancreas, regulation of gastric empyting and reduced appetite; all behaviors more typical of individuals without blood sugar control problems. Exenatide is self-regulating in that in lowers blood sugar when levels are elevated but does not continue to lower blood sugar when levels return to normal, unlike with sulfonylureas or insulins.|
|Mechanism of action||Exenatide is a functional analog of the human incretin Glucagon-Like Peptide-1 (GLP-1). Incretins enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. The GLP-1 system increases insulin secretion only in the presence of elevated plasma glucose levels, avoiding inappropriately high insulin levels during fasting. The drug also moderates peak serum glucagon levels during hyperglycemic periods following meals, but does not interfere with glucagon release in response to hypoglycemia. Secondary effects of drug administration reduces the rate of gastric emptying and decreases food intake, mitigating the potential severity of hyperglycemic events after meal|
|Following subcutaneous administration to patients with type 2 diabetes, exenatide reaches median peak plasma concentrations in 2.1 hours.|
Elosulfase alfa, BMN-110
APQPPNILLL LMDDMGWGDL GVYGEPSRET PNLDRMAAEG LLFPNFYSAN 50
PLCSPSRAAL LTGRLPIRNG FYTTNAHARN AYTPQEIVGG IPDSEQLLPE 100
LLKKAGYVSK IVGKWHLGHR PQFHPLKHGF DEWFGSPNCH FGPYDNKARP 150
NIPVYRDWEM VGRYYEEFPI NLKTGEANLT QIYLQEALDF IKRQARHHPF 200
FLYWAVDATH APVYASKPFL GTSQRGRYGD AVREIDDSIG KILELLQDLH 250
VADNTFVFFT SDNGAALISA PEQGGSNGPF LCGKQTTFEG GMREPALAWW 300
PGHVTAGQVS HQLGSIMDLF TTSLALAGLT PPSDRAIDGL NLLPTLLQGR 350
LMDRPIFYYR GDTLMAATLG QHKAHFWTWT NSWENFRQGI DFCPGQNVSG 400
VTTHNLEDHT KLPLIFHLGR DPGERFPLSF ASAEYQEALS RITSVVQQHQ 450
EALVPAQPQL NVCNWAVMNW APPGCEKLGK CLTPPESIPK KCLWSH 496
139-139′ 282-393 282′-393′ 463-492 463′-492′ 475-481 475′-481′
1 APRIL, 2013
BioMarin Pharmaceutical Inc. has submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for Vimizim (elosulfase alfa), an enzyme replacement therapy under evaluation for the treatment of patients with the rare lysosomal storage disorder mucopolysaccharidosis type IVA (MPS IVA), also called Morquio A syndrome. The company intends to submit an application for registration in the European Union (EU) by the end of April 2013.
“Based on the positive results from our Phase 3 pivotal study, we believe that Vimizim offers a substantial benefit to patients with MPS IVA, a severely debilitating and progressive disease for which there is no current treatment,” said Hank Fuchs, M.D., Chief Medical Officer of BioMarin. “The submission of the BLA represents a significant milestone for BioMarin and is the result of the strong, collaborative effort of many hard working employees, investigators, patients, and their families. With this application, BioMarin continues in its long-standing tradition of developing important therapies for those who are most in need. We look forward to working with the U.S. regulatory authorities to bring this treatment to patients.”
About MPS IVA
Mucopolysaccharidosis IVA (MPS IVA, also known as Morquio A Syndrome) is a disease characterized by deficient activity of N-acetylgalactosamine-6-sulfatase (GALNS) causing excessive lysosomal storage of glycosaminoglycans such as keratan sulfate and chondroitin sulfate. This excessive storage causes a systemic skeletal dysplasia, short stature, and joint abnormalities, which limit mobility and endurance. Malformation of the chest impairs respiratory function, and looseness of joints in the neck cause spinal instability and potentially spinal cord compression. Other symptoms may include hearing loss, corneal clouding, and heart disease. Initial symptoms often become evident in the first five years of life. The disease substantially limits both the quality and length of life of those affected.
The rate of incidence of MPS IVA is as yet unconfirmed and varies among different populations but estimates vary between 1 in 200,000 live births and 1 in 250,000 live births. The estimated prevalence is between 1,000 and 1,500 patients in the U.S., EU and Japan and between 1,500 to 2,000 patients in the rest of the world for a total of 2,500 to 3,000 patients.
BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. The company’s product portfolio comprises four approved products and multiple clinical and pre-clinical product candidates. Approved products include Naglazyme® (galsulfase) for mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin; Aldurazyme® (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation; Kuvan® (sapropterin dihydrochloride) Tablets, for phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck KGaA of Darmstadt, Germany; and Firdapse™ (amifampridine), which has been approved by the European Commission for the treatment of Lambert Eaton Myasthenic Syndrome (LEMS). Product candidates include BMN-110 (elosulfase alfa), formally referred to as GALNS, which successfully completed Phase III clinical development for the treatment of MPS IVA, PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase), which is currently in Phase II clinical development for the treatment of PKU, BMN-701, a novel fusion protein of insulin-like growth factor 2 and acid alpha glucosidase (IGF2-GAA), which is currently in Phase I/II clinical development for the treatment of Pompe disease, BMN-673, a poly ADP-ribose polymerase (PARP) inhibitor, which is currently in Phase I/II clinical development for the treatment of genetically-defined cancers, and BMN-111, a modified C-natriuretic peptide, which is currently in Phase I clinical development for the treatment of achondroplasia. For additional information, please visit www.BMRN.com. Information on BioMarin’s website is not incorporated by reference into this press release.
28 MAR 2013
The US FDA has accepted Merck’s biologics license application (BLA) for an investigational allergy immunotherapy tablet (AIT), Timothy grass pollen (Phleum pratense).
The application includes safety and efficacy data of the investigational sublingual dissolvable tablet from Phase III trials including a long-term, multi-season trial.
Merck Research Laboratories senior vice president, global scientific strategy, franchise head, infectious diseases and interim franchise head, respiratory & immunology Jeffrey Chodakewitz said, “We are pleased to have achieved this important milestone in the development of our investigational grass pollen AIT, which, if approved, would represent a potential new option for allergy specialists to offer appropriate allergic rhinitis patients.”
The grass pollen (Phleum pratense) AIT is designed to generate an immune response targeting the root cause of allergic rhinitis.
The company has collaborated with ALK-Abello for grass pollen (Phleum pratense) AIT development in North America.