ATC Group: A16AB Enzymes

Agalsidase alfa catalyses the hydrolysis of Gb3, cleaving a terminal galactose residue from the molecule. Treatment with the enzyme has been shown to reduce accumulation of Gb3 in many cell types including endothelial and parenchymal cells. Agalsidase alfa has been produced in a human cell line to provide for a human glycosylation profile that can influence uptake by mannose-6-phosphate receptors on the surface of target cells.

Agalsidase beta is a recombinant form of human α-galactosidase A and is produced by recombinant DNA technology using a mammalian Chinese Hamster Ovary (CHO) cell culture. The amino acid sequence of the recombinant form, as well as the nucleotide sequence which encoded it, are identical to the natural form of α-galactosidase.

Alglucerase was a biopharmaceutical drug for the treatment of Gaucher’s disease. It was a modified form of human β-glucocerebrosidase enzyme, where the non-reducing ends of the oligosaccharide chains have been terminated with mannose residues.

Alglucosidase alfa is an enzyme replacement therapy orphan drug for treatment of Pompe disease (Glycogen storage disease type II), a rare lysosomal storage disorder (LSD). It is postulated that alglucosidase alfa will restore lysosomal GAA activity resulting in stabilisation or restoration of cardiac and skeletal muscle function (including respiratory muscles). Due to the bloodbrain barrier effect and the enzyme’s size, uptake of alglucosidase alfa in the central nervous system is unlikely.

Asfotase alfa, a human recombinant tissue-nonspecific alkaline phosphatase-Fc-deca-aspartate fusion protein with enzymatic activity, promotes mineralisation of the skeleton in patients with hypophosphatasia.

Atidarsagene autotemcel is an ex vivo genetically modified autologous CD34+ hematopoietic stem and progenitor cell (HSPC) gene therapy. Autologous CD34+ HSPCs are collected from patient bone marrow (BM) harvest or from mobilised peripheral blood (mPB) and transduced with a lentiviral vector (ARSA LVV), which inserts one or more copies of the human ARSA complementary deoxyribonucleic acid (cDNA) into the cell’s genome, so that genetically modified cells become capable of expressing the functional ARSA enzyme.

Avalglucosidase alfa is a recombinant human acid α-glucosidase (rhGAA) that provides an exogenous source of GAA. Binding to M6P receptors on the cell surface has been shown to occur via carbohydrate groups on the GAA molecule, after which it is internalised and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity to degrade glycogen.

Cerliponase alfa is a recombinant form of human tripeptidyl peptidase-1 (rhTPP1). Cerliponase alfa is a proteolytic inactive proenzyme (zymogen) that is activated in the lysosome. The glycosylation profile of cerliponase alfa results in consistent cellular uptake and lysosomal targeting for activation.

Sipaglucosidase alfa is intended to replace the endogenous enzyme acid-alpha-glucosidase (GAA) that breaks down glycogen to glucose in the lysosome and is absent or impaired in Pompe disease. Sipaglucosidase alfa exerts enzymatic activity in the breakdown of glycogen and the reduction of intramuscular glycogen, as well as the amelioration of tissue damage.

Eladocagene exuparvovec is a gene therapy based on recombinant AAV2 vector containing the human cDNA for the DDC gene. After infusion into the putamen, the product results in the expression of the AADC enzyme and subsequent production of dopamine, and consequently, development of motor function in treated AADC-deficient patients.

Elosulfase alfa is a recombinant form of human N-acetylgalactosamine-6-sulfatase (rhGALNS) used for the treatment of mucopolysaccharidosis, type IVA (Morquio A Syndrome, MPS IVA). Elosulfase alfa 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.

Purified galsulfase, a recombinant form of human N-acetylgalactosamine 4-sulfatase, is a glycoprotein with a molecular weight of approximately 56 kD. Galsulfase is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Mucopolysaccharidosis VI (MPS VI; N-acetylgalactosamine 4-sulfatase deficiency; Maroteaux-Lamy syndrome).

Idursulfase (idursulfase) is a purified form of the lysosomal enzyme iduronate-2-sulfatase, produced in a human cell line providing a human glycosylation profile, which is analogous to the naturally occurring enzyme. Elaprase is indicated for the long-term treatment of patients with Hunter syndrome (Mucopolysaccharidosis II, MPS II).

Imiglucerase is a recombinant macrophage targeted acid β-glucosidase that replaces the deficient enzyme activity, hydrolysing glucosylceramide, thus correcting initial pathophysiology and preventing secondary pathology. Imiglucerase has been shown to improve both mental and physical aspects in the quality of life of Gaucher disease.

Laronidase is a recombinant form of human α-L-iduronidase and is produced by recombinant DNA technology. Laronidase is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Mucopolysaccharidosis I (MPS I; α-L-iduronidase deficiency) to treat the non-neurological manifestations of the disease.

Olipudase alfa is a recombinant human acid sphingomyelinase that reduces sphingomyelin (SM) accumulation in organs of patients with Acid Sphingomyelinase Deficiency (ASMD).

The active substance of pegunigalsidase alfa is pegunigalsidase alfa. Pegunigalsidase alfa is a pegylated recombinant form of human α-galactosidase-A. The amino acid sequence of the recombinant form is similar to the naturally occurring human enzyme. Pegunigalsidase alfa supplements or replaces α-galactosidase-A, reducing the amount of accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (Lyso-Gb3).

Pegvaliase is a PEGylated recombinant phenylalanine ammonia lyase enzyme that converts phenylalanine to ammonia and trans-cinnamic acid that are primarily eliminated by liver metabolism. It is indicated for the treatment of patients with phenylketonuria (PKU).

Pegzilarginase is a cobalt substituted recombinant human arginase 1 enzyme conjugated with mPEG carriers. The mPEG carrier reduces clearance of pegzilarginase resulting in an extended half-life while maintaining the functions of the enzyme. Pegzilarginase is intended to substitute for the deficient human arginase 1 enzyme activity in patients with ARG1-D. Pegzilarginase has been shown to rapidly and sustainably reduce plasma arginine and convert it to urea and ornithine.

Sacrosidase is a liquid enzyme preparation derived from baker’s yeast (Saccharomyces cerevisiae) used for the treatment of genetically determined sucrase deficiency, which is part of congenital sucrase-isomaltase deficiency (CSID).

Sebelipase alfa is a recombinant human lysosomal acid lipase (rhLAL). Replacement of LAL enzyme activity leads to reductions in liver fat content and transaminases, and enables metabolism of cholesteryl esters and triglycerides in the lysosome, leading to reductions in lowdensity lipoprotein (LDL) cholesterol and non-high-density lipoprotein (HDL) cholesterol, triglycerides, and increases in HDL cholesterol. Improvement in growth occurs as a result of substrate reduction in the intestine.

Taliglucerase alfa, a long term enzyme replacement therapy, is a recombinant analog of human lysosomal glucocerebrosidase that catalyzes the hydrolysis of glucocerebroside to glucose and ceramide, reducing the amount of accumulated glucocerebroside. It is used for the treatment of patients with a confirmed diagnosis of Type 1 Gaucher disease.

Velaglucerase alfa supplements or replaces beta-glucocerebrosidase, the enzyme that catalyzes the hydrolysis of glucocerebroside to glucose and ceramide in the lysosome, reducing the amount of accumulated glucocerebroside and correcting the pathophysiology of Gaucher disease. Velaglucerase alfa increases haemoglobin concentration and platelet counts and reduces liver and spleen volumes in patients with type 1 Gaucher disease.

Velmanase alfa is a recombinant form of human alpha-mannosidase. Velmanase alfa is intended to supplement or replace natural alpha-mannosidase, an enzyme that catalyses the sequential degradation of hybrid and complex high-mannose oligosaccharides in the lysosome, reducing the amount of accumulated mannose-rich oligosaccharides.

Vestronidase alfa is a recombinant form of human betaglucuronidase (GUS) and is intended to provide exogenous GUS enzyme for uptake into cellular lysosomes and subsequent catabolism of accumulated glycosaminoglycans (GAGs) in affected tissues.