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

References:

1. KEGG DRUG: Avalglucosidase alfa [Link]

Download FASTA Format

Synonyms

• Avalglucosidase alfa
• avalglucosidase alfa-ngpt
• Neo-recombinant human acid alpha-glucosidase
• NeoGAA

External IDs

• GZ-402666
• GZ402666

Poor quality drug data slowing you down?

Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.

Download eBook

Poor quality drug data slowing you down?

Download eBook

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 rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Late onset pompe disease		••••••••••••
Treatment of	Late onset pompe disease		••••••••••••			•••••••••
Treatment of	Pompe's disease		••••••••••••

Create Account

Associated Therapies

• Enzyme Replacement Therapy in Pompe Disease

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

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	ligand	Humans

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 C_max 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 outcomes

With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!

See the data

Improve decision support & research outcomes with our structured adverse effects data.

See a data sample

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 regions

Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.

Access now

Access drug product information from over 10 global regions.

Access now

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
Nexviadyme	Injection, powder, for solution	100 mg	Intravenous	Sanofi B.V.	2022-08-02	Not applicable
Nexviadyme	Injection, powder, for solution	100 mg	Intravenous	Sanofi B.V.	2022-08-02	Not applicable
Nexviadyme	Injection, powder, for solution	100 mg	Intravenous	Sanofi B.V.	2022-08-02	Not applicable
Nexviazyme	Powder, for solution	100 mg / vial	Intravenous	Sanofi Aventis	2022-02-09	Not applicable

Categories

ATC Codes

A16AB22 — Avalglucosidase alfa

• A16AB — Enzymes
• A16A — OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
• A16 — OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
• A — ALIMENTARY TRACT AND METABOLISM

Drug Categories

• Alimentary Tract and Metabolism
• Enzyme Replacement Therapy
• Enzymes
• Enzymes and Coenzymes
• Hydrolytic Lysosomal Glycogen-specific Enzyme

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

1. 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]
2. 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]
3. FDA Approved Drug Products: NEXVIAZYME (avalglucosidase alfa-ngpt) for injection, for intravenous use [Link]
4. FDA Press Announcements: FDA Approves New Treatment for Pompe Disease [Link]
5. KEGG DRUG: Avalglucosidase alfa [Link]
6. Newswire.ca: Nexviazyme™ (avalglucosidase alfa for injection) is now approved in Canada for patients with late-onset Pompe disease (acid α-glucosidase deficiency) [Link]
7. Health Canada Approved Drug Products: NEXVIAZYME (avalglucosidase alfa) for intravenous injection [Link]
8. EMA Approved Drug Products: Nexviadyme (avalglucosidase alfa) Intravenous Infusion [Link]

External Links

RxNav

2565814

Wikipedia

Avalglucosidase_alfa

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Glycogen Storage Disease Type II	1
3	Completed	Treatment	Glycogen Storage Disease Type II	1
3	Recruiting	Treatment	Glycogen Storage Disease Type II	1
2	Active Not Recruiting	Treatment	Glycogen Storage Disease Type II	1
2	Completed	Treatment	Glycogen Storage Disease Type II	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

Build, predict & validate machine-learning models

Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.

Learn more

Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.

Learn more

Details1. Cation-independent mannose-6-phosphate receptor

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

1. FDA Approved Drug Products: NEXVIAZYME (avalglucosidase alfa-ngpt) for injection, for intravenous use [Link]

×

Identify potential medication risks

Easily compare up to 40 drugs with our drug interaction checker.

Get severity rating, description, and management advice.

Learn more

Drug created at December 15, 2020 18:05 / Updated at December 01, 2022 11:30