Vestronidase alfa
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Identification
- Summary
Vestronidase alfa is a recombinant beta-glucuronidase used to treat mucopolysaccharidosis VII.
- Brand Names
- Mepsevii
- Generic Name
- Vestronidase alfa
- DrugBank Accession Number
- DB12366
- Background
Vestronidase alfa, or vestronidase alfa-vjbk, is a recombinant human lysosomal beta glucuronidase that is a purified enzyme produced by recombinant DNA technology in a Chinese hamster ovary cell line. The enzyme is a homotetramer consisted of 4 monomers with 629 amino acids, and holds the same amino acid sequence as human beta-glucuronidase (GUS) Label. Vestronidase alfa is an enzyme replacement therapy for the treatment of mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, which is an inherited, rare genetic metabolic condition that targets a small subset of population. MPS VII is a progressive condition that affects most tissues and organs due to the lack of a lysosomal enzyme called beta-glucuronidase, leading to buildup of toxic metabolites. The disorder is initiated with skeletal abnormalities, including short stature, along with other pathological conditions including enlarged liver and spleen, heart valve abnormalities, and narrowed airways which can lead to lung infections and trouble breathing. Last two conditions are leading causes of fatalities in patients with MPS VII.
Some affected individuals do not survive infancy, while others may live into adolescence or adulthood and patients may experience developmental delay and progressive intellectual disability Label. In clinical trials, vestronidase alfa treatment demonstrated improvement and stabilization in motor symptoms by increasing the patients' ability to walk longer distances in comparison to treatment with placebo . Few patients also experienced improved pulmonary function.
Vestronidase alfa was FDA-approved on November 17th, 2017 under the trade name Mepsevii as an intravenous infusion for the treatment of pediatric and adult patients.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Recombinant Enzymes - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 72562.0 Da (Non-glycosylated)
- Sequences
- Not Available
- Synonyms
- Recombinant human beta-glucuronidase
- Vestronidase alfa
- Vestronidase alfa-vjbk
- External IDs
- UX-003
- UX003
Pharmacology
- Indication
Indicated in pediatric and adult patients for the treatment of Mucopolysaccharidosis VII (MPS VII, Sly syndrome).
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Mucopolysaccharidosis vii •••••••••••• •••••• ••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
In all patients evaluated, MEPSEVII treatment resulted in reduction of urinary excretion of GAGs including chondroitin sulfate and dermatan sulfate, which was sustained with continued treatment Label.
- Mechanism of action
Beta-glucuronidase (GUS) is a lysosomal enzyme responsible for degradation of glucuronate-containing glycosaminoglycan (GAG) 2. Resulting lysosomal storage and GAG accumulation in cells from incomplete metabolic degradation of macromolecules leads to damage to multiple tissues and organs. Vestronidase alfa serves as an exogenous source of GUS enzyme for uptake into cellular lysosomes, which is facilitated by the presence of mannose-6-phosphate (M6P) residues on the oligosaccharide chains of the recombinant enzyme. The chains allow binding of the enzyme to cell surface receptors to promote cellular uptake, and targets the lysosomes to achieve catabolism of accumulated GAGs in affected tissues Label.
- Absorption
Serum exposures of vestronidase alfa increases in a dose-proportional manner, from 1 mg/kg (0.25 times the approved recommended dosage) to 2 mg/kg (0.5 times the approved recommended dosage), and 4 mg/kg (the recommended dosage). After repeated dosing of 4 mg/kg every other week in patients with MPS VII, the mean ± standard deviation of maximal concentration (Cmax) was 20.0 ± 8.1 mcg/mL (range: 6.6 to 34.9 mcg/mL). The mean ± standard deviation of area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) was 3440 ± 1430 mcg x min/mL (range: 1130 to 5820 mcg x min/mL) Label.
- Volume of distribution
After repeated dosing of 4 mg/kg every other week in MPS VII patients, the mean ± standard deviation of the total volume of distribution (Vss) was 260 ± 130 mL/kg (range: 97 to 598 mL/kg) Label.
- Protein binding
Not Available
- Metabolism
Vestronidase alfa is eliminated by nonspecific proteolytic degradation into small peptides and amino acids Label.
- Route of elimination
Vestronidase alfa-vjbk is not expected to be eliminated through renal or fecal excretion. No excretion studies have been conducted Label.
- Half-life
After repeated dosing of 4 mg/kg every other week in MPS VII patients, the mean ± standard deviation of the elimination half-life (t1/2) was 155 ± 37 minutes (range: 51 to 213 minutes) Label.
- Clearance
After repeated dosing of 4 mg/kg every other week in MPS VII patients, the mean ± standard deviation of the total clearance (CL) was 1.3 ± 0.7 mL/min/kg (range: 0.6 to 3.3 mL/min/kg) Label.
- Adverse Effects
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- Toxicity
Treatment of vestronidase alfa with doses up to 20 mg/kg administered weekly in rats did not result in adverse effect on fertility and reproductive performance of male and female rats. Studies assessing the mutagenic or carcinogenic potential of vestronidase alfa have not been performed Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Mepsevii Injection 2 mg/1mL Intravenous Ultragenyx Pharmaceutical Inc. 2017-11-15 Not applicable US Mepsevii Injection, solution, concentrate 2 mg/ml Intravenous Ultragenyx Germany Gmbh 2020-12-16 Not applicable EU
Categories
- ATC Codes
- A16AB18 — Vestronidase alfa
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 7XZ4062R17
- CAS number
- 1638194-78-1
References
- General References
- Basinska A, Florianczyk B: Beta-glucuronidase in physiology and disease. Ann Univ Mariae Curie Sklodowska Med. 2003;58(2):386-9. [Article]
- Naz H, Islam A, Waheed A, Sly WS, Ahmad F, Hassan I: Human beta-glucuronidase: structure, function, and application in enzyme replacement therapy. Rejuvenation Res. 2013 Oct;16(5):352-63. doi: 10.1089/rej.2013.1407. [Article]
- External Links
- PubChem Substance
- 347911326
- 1989818
- Wikipedia
- Vestronidase_alfa
- FDA label
- Download (369 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Available Not Available Mucopolysaccharidosis Type VII / Sly Syndrome 1 somestatus stop reason just information to hide Not Available No Longer Available Not Available Mucopolysaccharidosis Type VII 1 somestatus stop reason just information to hide 3 Completed Treatment MPS 7 / Mucopolysaccharidosis (MPS) / Mucopolysaccharidosis Type VII / Sly Syndrome 1 somestatus stop reason just information to hide 3 Completed Treatment Mucopolysaccharidosis (MPS) / Mucopolysaccharidosis Type VII / Sly Syndrome 1 somestatus stop reason just information to hide 2 Completed Treatment Mucopolysaccharidosis (MPS) / Mucopolysaccharidosis Type VII / Sly Syndrome 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 2 mg/1mL Injection, solution, concentrate Intravenous 2 MG/ML - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Drug created at October 20, 2016 22:05 / Updated at May 27, 2021 02:57