Avalglucosidase alfa
Identification
- Summary
Avalglucosidase alfa is a lysosomal glycogen-specific enzyme that is used to treat patients one year of age and older with late-onset Pompe disease, or lysosomal acid alpha-glucosidase (GAA) deficiency.
- Brand Names
- Nexviazyme
- Generic Name
- Avalglucosidase alfa
- DrugBank Accession Number
- DB16099
- Background
Avalglucosidase alfa, or NeoGAA, is a drug for enzyme replacement therapy specifically designed for Pompe disease, a rare inherited neuromuscular disorder caused by the deficiency of the alpha-glucosidase (GAA) enzyme. GAA is an essential enzyme that hydrolyzes glycogen into free glucose for use in cellular functions. In Pompe disease, the GAA enzyme is missing and patients are unable to properly break down glycogen, resulting in the accumulation of glycogen within lysosomes and progressive disruption of cellular function, especially in smooth, cardiac, and skeletal muscle cells. Pompe disease is characterized by progressive muscle weakness and loss of motor function, including respiratory muscle weakness, which leads to premature death and debilitating effects on people’s lives.1 Avalglucosidase alfa is a recombinant form of GAA that restores deficient enzyme levels. First developed by Sanofi Genzyme, avalglucosidase alfa is a chemically modified version of alglucosidase alfa, where synthetic bis-phosphorylated oligosaccharides were attached to the structure to improve cellular uptake of the drug and better muscle targeting.2
On August 6, 2021, avalglucosidase alfa-ngpt was approved by the FDA under the market name Nexviazyme to treat patients one year of age and older with late-onset Pompe disease.4 Late-onset Pompe disease is associated with a range of debilitating physical symptoms, such as progressive muscle weakness, including respiratory muscle weakness, and loss of motor function.1 In clinical trials, avalglucosidase alfa improved lung function in patients with Pompe disease.4 Avalglucosidase alfa was approved by Health Canada on November 15, 2021 for the treatment of patients older than six months of age with late-onset Pompe disease.6 The EMA approved the drug on June 24, 2022.8
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Recombinant Enzymes - Protein Chemical Formula
- C4490H6818N1197O1299S32
- Protein Average Weight
- 124000.0 Da (approximate)
- Sequences
>Avalglucosidase alfa protein sequence QQGASRPGPRDAQAHPGRPRAVPTQCDVPPNSRFDCAPDKAITQEQCEARGCCYIPAKQG LQGAQMGQPWCFFPPSYPSYKLENLSSSEMGYTATLTRTTPTFFPKDILTLRLDVMMETE NRLHFTIKDPANRRYEVPLETPRVHSRAPSPLYSVEFSEEPFGVIVHRQLDGRVLLNTTV APLFFADQFLQLSTSLPSQYITGLAEHLSPLMLSTSWTRITLWNRDLAPTPGANLYGSHP FYLALEDGGSAHGVFLLNSNAMDVVLQPSPALSWRSTGGILDVYIFLGPEPKSVVQQYLD VVGYPFMPPYWGLGFHLCRWGYSSTAITRQVVENMTRAHFPLDVQWNDLDYMDSRRDFTF NKDGFRDFPAMVQELHQGGRRYMMIVDPAISSSGPAGSYRPYDEGLRRGVFITNETGQPL IGKVWPGSTAFPDFTNPTALAWWEDMVAEFHDQVPFDGMWIDMNEPSNFIRGSEDGCPNN ELENPPYVPGVVGGTLQAATICASSHQFLSTHYNLHNLYGLTEAIASHRALVKARGTRPF VISRSTFAGHGRYAGHWTGDVWSSWEQLASSVPEILQFNLLGVPLVGADVCGFLGNTSEE LCVRWTQLGAFYPFMRNHNSLLSLPQEPYSFSEPAQQAMRKALTLRYALLPHLYTLFHQA HVAGETVARPLFLEFPKDSSTWTVDHQLLWGEALLITPVLQAGKAEVTGYFPLGTWYDLQ TVPIEALGSLPPPPAAPREPAIHSEGQWVTLPAPLDTINVHLRAGYIIPLQGPGLTTTES RQQPMALAVALTKGGEARGELFWDDGESLEVLERGAYTQVIFLARNNTIVNELVRVTSEG AGLQLQKVTVLGVATAPQQVLSNGVPVSNFTYSPDTKVLDICVSLLMGEQFLVSWC
Download FASTA FormatReferences:
- KEGG DRUG: Avalglucosidase alfa [Link]
- Synonyms
- Avalglucosidase alfa
- avalglucosidase alfa-ngpt
- Neo-recombinant human acid alpha-glucosidase
- NeoGAA
- External IDs
- GZ-402666
- GZ402666
Pharmacology
- Indication
Avalglucosidase alfa is a hydrolytic lysosomal glycogen-specific enzyme indicated for the treatment of patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency).3,7,8 In the US, it is approved in patients one year of age and older. 3
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
- Associated Therapies
- Contraindications & Blackbox Warnings
- Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.
- Pharmacodynamics
Avalglucosidase alfa is a recombinant alpha-glucosidase (GAA) enzyme that catalyzes hydrolysis of glycogen. In clinical trials, avalglucosidase alfa reduced the levels of glycogen excreted in the urine of patients with Pompe disease, indicating that it effectively cleaved excess glycogen.3 Avalglucosidase alfa has significantly higher binding affinity for cation-independent mannose-6-phosphate receptor (CI-MPR) for cellular uptake and better muscle targeting than alglucosidase alfa. In GAA-deficient mice, avalglucosidase alfa reduced glycogen with more efficacy than alglucosidase alfa at an equivalent dose.2
- Mechanism of action
Pompe disease is a genetic glycogen metabolism disorder that is also referred to as acid maltase deficiency or glycogen storage disease type II (GSD II). It is caused by mutations in the GAA gene, which encodes the lysosomal hydrolase acid α-glucosidase (GAA), an enzyme that normally catalyzes hydrolysis of glycogen to release free glucose for absorption and use for cellular functions. GAA deficiency leads to accumulation of glycogen within lysosomes and progressive disruption of cellular function, especially in smooth, cardiac, and skeletal muscle cells.1
Enzyme replacement therapy using avalglucosidase alfa aims to restore the missing GAA enzyme. Avalglucosidase alfa is a hydrolytic lysosomal glycogen-specific recombinant human GAA enzyme that is conjugated with multiple synthetic bis-mannose-6-phosphate (bis-M6P) tetra-mannose glycans for enhanced targeting to skeletal muscles. The M6P of avalglucosidase alfa binds to cation-independent mannose-6-phosphate receptor (CI-MPR) on the cell surface with high affinity, which allows drug uptake into cells. Avalglucosidase alfa is internalized and transported into lysosomes to undergo proteolytic cleavage. It then exerts GAA enzymatic activity to cleave glycogen.1,3
Target Actions Organism NCation-independent mannose-6-phosphate receptor ligandHumans - Absorption
The avalglucosidase alfa-ngpt exposure increases in an approximately proportional manner with increasing doses over a range from 5 to 20 mg/kg. Following intravenous infusion of 20 mg/kg every two weeks in patients with late-onset Pompe disease, the mean ± SD plasma Cmax of avalglucosidase alfa-ngpt was 259 ± 72 µg/mL at week one and 242 ± 81 µg/mL at week 49. The mean ± SD plasma AUC of avalglucosidase alfa-ngpt was 1,290 ± 420 µg∙h/mL at week one and 1,250 ± 433 µg∙h/mL at week 49.3
- Volume of distribution
The volume of distribution of avalglucosidase alfa-ngpt was 3.4 L in patients with late-onset Pompe disease. No accumulation was observed following every two weeks-dosing schedules.3
- Protein binding
There is limited information on drug protein binding.
- Metabolism
The metabolic pathway of avalglucosidase alfa-ngpt has not been characterized. The protein portion of avalglucosidase alfa-ngpt is expected to be metabolized into small peptides and amino acids via catabolic pathways.3
- Route of elimination
There is limited information on drug elimination.
- Half-life
The mean avalglucosidase alfa-ngpt plasma elimination half-life was 1.6 hours in patients with late-onset Pompe disease.3
- Clearance
The mean avalglucosidase alfa-ngpt clearance was 0.9 L/hour in patients with late-onset Pompe disease.3
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
There is limited information on the overdose profile and LD50 values of avalglucosidase alfa.
- 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.
- International/Other Brands
- Nexviazyme (Sanofi Genzyme)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Nexviadyme Injection, powder, for solution 100 mg Intravenous Sanofi B.V. 2022-08-02 Not applicable EU Nexviadyme Injection, powder, for solution 100 mg Intravenous Sanofi B.V. 2022-08-02 Not applicable EU Nexviadyme Injection, powder, for solution 100 mg Intravenous Sanofi B.V. 2022-08-02 Not applicable EU Nexviadyme Injection, powder, for solution 100 mg Intravenous Sanofi B.V. 2022-08-02 Not applicable EU Nexviazyme Powder, for solution 100 mg / vial Intravenous Sanofi Aventis 2022-02-09 Not applicable Canada Nexviazyme ngpt Injection, powder, lyophilized, for solution 100 mg/10mL Intravenous Genzyme Corporation 2021-08-06 Not applicable US
Categories
- ATC Codes
- A16AB22 — Avalglucosidase 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
- Humans and other mammals
Chemical Identifiers
- UNII
- EO144CP0X9
- CAS number
- 1802558-87-7
References
- General References
- Xu S, Lun Y, Frascella M, Garcia A, Soska R, Nair A, Ponery AS, Schilling A, Feng J, Tuske S, Valle MCD, Martina JA, Ralston E, Gotschall R, Valenzano KJ, Puertollano R, Do HV, Raben N, Khanna R: Improved efficacy of a next-generation ERT in murine Pompe disease. JCI Insight. 2019 Mar 7;4(5). pii: 125358. doi: 10.1172/jci.insight.125358. eCollection 2019 Mar 7. [Article]
- Do HV, Khanna R, Gotschall R: Challenges in treating Pompe disease: an industry perspective. Ann Transl Med. 2019 Jul;7(13):291. doi: 10.21037/atm.2019.04.15. [Article]
- FDA Approved Drug Products: NEXVIAZYME (avalglucosidase alfa-ngpt) for injection, for intravenous use [Link]
- FDA Press Announcements: FDA Approves New Treatment for Pompe Disease [Link]
- KEGG DRUG: Avalglucosidase alfa [Link]
- Newswire.ca: Nexviazyme™ (avalglucosidase alfa for injection) is now approved in Canada for patients with late-onset Pompe disease (acid α-glucosidase deficiency) [Link]
- Health Canada Approved Drug Products: NEXVIAZYME (avalglucosidase alfa) for intravenous injection [Link]
- EMA Approved Drug Products: Nexviadyme (avalglucosidase alfa) Intravenous Infusion [Link]
- External Links
- 2565814
- Wikipedia
- Avalglucosidase_alfa
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Recruiting Treatment Glycogen Storage Disease Type II 1 3 Active Not Recruiting Treatment Glycogen Storage Disease Type II;Pompe's Disease 1 3 Recruiting Treatment Glycogen Storage Disease Type II 1 2 Active Not Recruiting Treatment Glycogen Storage Disease Type II;Pompe's Disease 1 2, 3 Completed Treatment Glycogen Storage Disease Type II;Pompe's Disease 1 1 Completed Treatment Glycogen Storage Disease Type II (GSD II) / Pompe's Disease 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 100 mg Powder, for solution Intravenous 100 mg / vial Injection, powder, lyophilized, for solution Intravenous 100 mg/10mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Ligand
- General Function
- Transporter activity
- Specific Function
- Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate r...
- Gene Name
- IGF2R
- Uniprot ID
- P11717
- Uniprot Name
- Cation-independent mannose-6-phosphate receptor
- Molecular Weight
- 274372.42 Da
References
- FDA Approved Drug Products: NEXVIAZYME (avalglucosidase alfa-ngpt) for injection, for intravenous use [Link]
Drug created at December 15, 2020 18:05 / Updated at December 01, 2022 11:30