ChEMBL

On 26th February, FDA has approved Velaglucerase Alfa, under the trade name VPRIV. Velaglucerase Alfa, is a hydrolytic lysosomal glucocerebroside-specific enzyme indicated for long-term enzyme replacement therapy (ERT) for patients with type 1 Gaucher disease. Gaucher's disease is an autosomal recessive disorder characterized by a deficiency of the lysosomal enzyme beta-glucocerebrosidase (UniProt: P04062) (E.C. 3.2.1.45) (this enzyme is also known as glucosylceramidase, β-glucosidase, and D-glucosyl-N-acylsphingosine glucohydrolase).
Velaglucerase Alfa ATC code is A16AB10.
Glucocerebrosidase catalyses the hydrolysis of the glycolipid glucocerebroside, which is an intermediate in the glycolipid metabolism. Deficiency in this enzyme causes accumulation in the liver, spleen, bones, bone marrow and nervous system and can prevent cells and organs from working properly. Velaglucerase Alfa works by catalysing the hydrolysis of glucocerebroside, reducing the amount of accumulated glucocerebroside. Velaglucerase Alfa has the same amino acid sequence as the naturally occurring human enzyme, glucocerebrosidase. It contains 5 potential N-linked glycosylation sites, with four of these sites occupied by glycan chains. Velaglucerase Alfa is manufactured to contain predominantly high mannose-type N-linked glycan chains (and this difference in the mannose chains differentiates the very closely related drug Imiglucerase from Velagucerase alfa). These high mannose N-linked glycan chains are specifically recognized and internalised via the mannose receptor present on the surface of the cells that accumulate glucocerebroside in Gaucher disease.

>P04062|40-536
ARPCIPKSFGYSSVVCVCNATYCDSFDPPTFPALGTFSRYESTRSGRRME
LSMGPIQANHTGTGLLLTLQPEQKFQKVKGFGGAMTDAAALNILALSPPA
QNLLLKSYFSEEGIGYNIIRVPMASCDFSIRTYTYADTPDDFQLHNFSLP
EEDTKLKIPLIHRALQLAQRPVSLLASPWTSPTWLKTNGAVNGKGSLKGQ
PGDIYHQTWARYFVKFLDAYAEHKLQFWAVTAENEPSAGL

Several structures of glucocerebrosidase are known (an example is PDB: 1OGS)
Other similar therapies include ERT with Imiglucerase (approved in 1994 under the trade name Cerezyme) and pharmacological chaperoning, which involves the use of orally administered drugs, like for example Miglustat (approved in 2003 under the trade name Zavesca), which works by inhibiting glucocerebroside synthase. Velaglucerase Alfa is a glycoprotein of 497 amino acids, with a molecular weight of ca. 63 kDa. It has a mean half-life of 11 to 12 minutes, a mean clearance ranging from 6.72 to 7.56 mL/min/kg and a mean volume of distribution (Vd) ranging from 82 to 108 mL/kg. The recommended dosage is 60 Units/kg administrated every other week as a 60-minute intravenous infusion. The full prescribing information can be found here. Velaglucerase Alfa is manufactured by Shire Human Genetic Therapies, Inc. and the product website is www.vpriv.com.