BIOCHEMISTRY, BIOMEDICINE & PHARMACEUTICS

LUMIZYME (alglucosidase alfa) for injection, for intravenous use Pompe disease (acid maltase deficiency, glycogen storage disease type II, GSD II, glycogenosis type II) is an inherited disorder of glycogen metabolism caused by the absence or marked deficiency of the lysosomal enzyme GAA. LUMIZYME provides an exogenous source of GAA. Binding to mannose-6-phosphate receptors on the cell surface has been shown to occur via carbohydrate groups on the GAA molecule, after which it is internalized and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity. It then exerts enzymatic activity in cleaving glycogen.  Initial U.S. Approval: 2010 INDICATIONS AND USAGE LUMIZYME (alglucosidase alfa) is a lysosomal glycogen-specific enzyme indicated for patients 8 years and older with late (non-infantile) onset Pompe disease (GAA deficiency) who do not have evidence of cardiac hypertrophy. The safety and efficacy of LUMIZYME have no...

                  Aglucosidase (Myozyme)for the Treatment of Pompe Disease MYOZYME® (alpha-l-glucosidase alfa) Injectable for intravenous infusion: Pompe disease (glycogen storage disease type II, GSD II, glycogenosis type II, acid maltase deficiency) is an inherited disorder of glycogen metabolism caused by the absence or marked deficiency of the lysosomal enzyme GAA.  MYOZYME provides an exogenous source of GAA. Binding to mannose-6-phosphate receptors on the cell surface has been shown to occur via carbohydrate groups on the GAA molecule, after which it is internalized and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity. It then exerts enzymatic activity in cleaving glycogen.  Initial U.S. Approval: 2006 INDICATIONS AND USAGE: MYOZYME® (alglucosidase alfa) is a lysosomal glycogen-specific enzyme indicated for use in patients with Pompe disease (GAA deficiency...

ELAPRASE® (idursulfase) injection, for intravenous use Hunter syndrome (Mucopolysaccharidosis II, MPS II) is an X-linked recessive disease caused by insufficient levels of the lysosomal enzyme iduronate-2-sulfatase. This enzyme cleaves the terminal 2-O-sulfate moieties from the glycosaminoglycans (GAG) dermatan sulfate and heparan sulfate. Due to the missing or defective iduronate-2-sulfatase enzyme in patients with Hunter syndrome, GAG progressively accumulate in the lysosomes of a variety of cells, leading to cellular engorgement, organomegaly, tissue destruction, and organ system dysfunction. ELAPRASE is a formulation of idursulfase, a purified form of human iduronate-2-sulfatase, a lysosomal enzyme. Idursulfase is produced by recombinant DNA technology in a human cell line. ELAPRASE is intended to provide exogenous enzyme for uptake into cellular lysosomes. Mannose-6-phosphate (M6P) residues on the oligosaccharide chains allow binding of the enzyme to the M6P receptors on ...

VIMIZIM (elosulfase alfa) injection, for intravenous use Mucopolysaccharidoses comprise a group of lysosomal storage disorders caused by the deficiency of specific lysosomal enzymes required for the catabolism of glycosaminoglycans (GAG). Mucopolysaccharidosis IVA (MPS IVA, Morquio A Syndrome) is characterized by the absence or marked reduction in N-acetylgalactosamine-6-sulfatase activity. The sulfatase activity deficiency results in the accumulation of the GAG substrates, KS and C6S, in the lysosomal compartment of cells throughout the body. The accumulation leads to widespread cellular, tissue, and organ dysfunction. Vimizim is intended to provide the exogenous enzyme N-acetylgalactosamine-6-sulfatase that will be taken up into the lysosomes and increase the catabolism of the GAGs KS and C6S. Vimizim is a formulation of elosulfase alfa, which is a purified human enzyme produced by recombinant DNA technology in a Chinese hamster ovary cell line. Human N-acetylgalactosamine-6-sul...

Mucopolysaccharide storage disorders are caused by the deficiency of specific lysosomal enzymes required for the catabolism of GAG. Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) is characterized by the absence or marked reduction in N–acetylgalactosamine 4-sulfatase. The sulfatase activity deficiency results in the accumulation of the GAG substrate, dermatan sulfate, throughout the body. This accumulation leads to widespread cellular, tissue, and organ dysfunction. NAGLAZYME is intended to provide an exogenous enzyme that will be taken up into lysosomes and increase the catabolism of GAG. Galsulfase uptake by cells into lysosomes is most likely mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of galsulfase to specific mannose-6-phosphate receptors. NAGLAZYME (galsulfase) is a normal variant form of the polymorphic human enzyme, N–acetylgalactosamine 4-sulfatase that is produced by recombinant DNA technology in a Chinese hamster ov...

Ceredase® (alglucerase injection) Ceredase® (alglucerase injection) is a modified form of the enzyme, ß-glucocerebrosidase ß-D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45). Alglucerase is a monomeric glycoprotein of 497 amino acids with carbohydrates making up approximately 6% of the molecule (Mr = 59,300 as determined by SDS-PAGE). The unmodified enzyme (ß-glucocerebrosidase) also contains 497 amino acids and contains approximately 12% carbohydrate (Mr = 67,000). The carbohydrates on the unmodified enzyme consist of N-linked carbohydrate chains of the complex and high mannose type. Glucocerebrosidase and alglucerase catalyze the hydrolysis of the glycolipid, glucocerebroside, within the lysosomes of the reticuloendothelial system. Alglucerase is prepared by modification of the oligosaccharide chains of human ß-glucocerebrosidase. The modification alters the sugar residues at the non-reducing ends of the oligosaccharide chains of the glycoprotein so that they are predominant...

ALDURAZYME (laronidase) Solution for intravenous infusion only Mucopolysaccharide storage disorders are caused by the deficiency of specific lysosoma l enzymes required for the catabolism of glycosaminoglycans (GAG). Mucopolysaccharidosis I (MPS I) is characterized by the deficiency of a-L-iduronidase, a lysosomal hydrolase which catalyses the hydrolysis of terminal a-L-iduronic acid residues of dermatan sulfate and heparan sulfate. Reduced or absent a-L-iduronidase activity results in the accumulation of the GAG substrates, dermatan sulfate and heparan sulfate, throughout the body and leads to widespread cellular, tissue, and organ dysfunction.  ALDURAZYME (laronidase) is a polymorphic variant of the human enzyme, a-L-iduronidase that is produced by recombinant DNA technology in a Chinese hamster ovary cell line. a-L-iduronidase (glycosaminoglycan a-L-iduronohydrolase, EC 3.2.1.76) is a lysosomal hydrolase that catalyses the hydrolysis of terminal a-L-iduronic acid residues o...

VPRIV™ (velaglucerase alfa for injection) Gaucher disease is an autosomal recessive disorder caused by mutations in the GBA gene, which results in a deficiency of the lysosomal enzyme beta-glucocerebrosidase. Glucocerebrosidase catalyzes the conversion of the sphingolipid glucocerebroside into glucose and ceramide. The enzymatic deficiency causes an accumulation of glucocerebroside primarily in the lysosomal compartment of macrophages, giving rise to foam cells or "Gaucher cells". In this lysosomal storage disorder (LSD), clinical features are reflective of the accumulation of Gaucher cells in the liver, spleen, bone marrow, and other organs. The accumulation of Gaucher cells in the liver and spleen leads to organomegaly. The presence of Gaucher cells in the bone marrow and spleen leads to clinically significant anemia and thrombocytopenia. Velaglucerase alfa is a glycoprotein of 497 amino acids; with a molecular weight of approximately 63 kDa. Velaglucerase alfa has th...

ELELYSO (taliglucerase alfa) for injection, for intravenous use: Taliglucerase alfa, is a hydrolytic lysosomal glucocerebroside-specific enzyme for intravenous infusion in  patients with 'Gaucher disease' (rare genetic disorder). The drug is a recombinant active form of the lysosomal enzyme, β-glucocerebrosidase, which is expressed in genetically modified carrot plant root cells cultured in a disposable bioreactor system (ProCellEx®). It is the first 'plant made' drug approved by the U.S Food and Drug administration (FDA). β-Glucocerebrosidase (β-D-glucosyl-N-acylsphingosine glucohydrolase, E.C. 3.2.1.45) is a lysosomal glycoprotein enzyme that catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide.  ELELYSO is produced by recombinant DNA technology using plant cell culture (carrot). Purified taliglucerase alfa is a monomeric glycoprotein containing 4 Nlinked glycosylation sites (Mr = 60,800) ELELYSO catalyzes the hydrolysis of ...

Fabrazyme (agalsidase beta) Injection, powder, lyophilized for solution for intravenous use Fabry disease is an X-linked genetic disorder of glycosphingolipid metabolism. Deficiency of the lysosomal enzyme α-galactosidase A leads to progressive accumulation of glycosphingolipids, predominantly GL-3, in many body tissues, starting early in life and continuing over decades. Clinical manifestations of Fabry disease include renal failure, cardiomyopathy, and cerebrovascular accidents.  Accumulation of GL-3 in renal endothelial cells may play a role in renal failure. Fabrazyme® (agalsidase beta) is intended to provide an exogenous source of α-galactosidase A in Fabry disease patients. Nonclinical and clinical studies evaluating a limited number of cell types indicate that Fabrazyme will catalyze the hydrolysis of glycosphingolipids, including GL-3. Initial U.S. Approval: 2003 RECENT MAJOR CHANGES Warnings and Precautions, Anaphylaxis and Allergic Reactions 2008 INDICATIONS AN...

KANUMA (sebelipase alfa) injection, for intravenous use KANUMA (sebelipase alfa) is a recombinant human lysosomal acid lipase (rhLAL). Lysosomal acid lipase (EC 3.1.1.13) is a lysosomal glycoprotein enzyme that catalyzes the hydrolysis of cholesteryl esters to free cholesterol and fatty acids and the hydrolysis of triglycerides to glycerol and free fatty acids. KANUMA is produced by recombinant DNA technology in the egg white of eggs laid by genetically engineered chickens. Purified sebelipase alfa is a monomeric glycoprotein containing 6 N-linked glycosylation sites and has a molecular mass of approximately 55,000 daltons. The amino acid sequence for sebelipase alfa is the same as the amino acid sequence for human LAL.  Sebelipase alfa binds to cell surface receptors in the hepatocytes 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 choles...