Avalglucosidase alfa

Not to be confused with Alglucosidase alfa.
Avalglucosidase alfa
Names
Trade namesNexviazyme, Nexviadyme
Other namesGZ-402666, avalglucosidase alfa-ngpt
Clinical data
Drug classEnzyme[1]
Main usesGlycogen storage disease type II (Pompe disease)[1]
Side effectsHeadache, tiredness, diarrhea, nausea, joint pain, dizziness, muscle pain, itchiness, shortness of breath, skin redness[2]
Pregnancy
category
    Routes of
    use    		Intravenous
    Typical dose20-40 mg/kg q 2 weeks[2]
    External links
    AHFS/Drugs.comMonograph
    US NLMAvalglucosidase alfa
    Legal
    License data
    Legal status
    Chemical and physical data
    FormulaC4490H6818N1197O1299S32
    Molar mass99376.93 g·mol−1

    Avalglucosidase alfa, sold under the brand name Nexviazyme, is a medication used to treat glycogen storage disease type II (Pompe disease).[2][1] It is used in those over the age of one with late onset disease.[2] It is given gradually into a vein every two weeks.[1]

    Common side effects include headache, tiredness, diarrhea, nausea, joint pain, dizziness, muscle pain, itchiness, shortness of breath, and skin redness.[2] Other side effects may include anaphylaxis, infusion reaction, and cardiorespiratory failure.[2] It is an enzyme replacement therapy, specifically to replace alpha-glucosidase.[1] It is a hydrolytic lysosomal glycogen-specific enzyme.[2]

    Avalglucosidase alfa was approved for medical use in the United States in 2021 and Europe in 2022.[1] It costs about 900 USD per 50-mg in the United States as of 2021.[8] In Canada it costs about 525,000 CAD per person per year as of 2022.[9]

    Medical uses

    Avalglucosidase alfa is indicated for the treatment of people aged one year and older with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency).[2][7] It appears to be at least as effective as alglucosidase alfa.[1]

    Dosage

    For those who weight less than 30 kg a dose of 40 mg/kg is used.[2] For those who weight more than 30 kg a dose of 20 mg/kg is used.[2] It is given every two weeks.[2]

    Side effects

    Avalglucosidase alfa has a blackbox warning for hypersensitivity, infusion-related reactions, and cardiorespiratory failure.[10]

    Mechanism of action

    People with Pompe disease have an enzyme deficiency that leads to the accumulation of a complex sugar, called glycogen, in skeletal and heart muscles, which causes muscle weakness and premature death from respiratory or heart failure.[7]

    Avalglucosidase alfa is composed of the human GAA enzyme that is conjugated with a couple of bis-mannose-6-phosphate (bis-M6P) tetra-mannose glycans.[10] The bis-MGP of avalglucosidase alpha binds to the cation-independent mannose-6-phosphate receptor which is located on the skeletal muscles.[10] Once the molecule binds to the receptor, the drug enters the cell. The drug then enters the lysosomes of the cell.[10] Within the lysosome of the cell, the drugs undergoes cleavage proteolytically and then acts as an enzyme.[10]

    Pharmacokinetics

    The volume of distribution of avalglucosidase alfa was 3.4 L in patients who had Pompe disease of a late onset.[10] The average half-life of avalglucosidase alfa was 1.6 hours, measured in patients with late stage Pompe disease.[10] There is little information availible on the metabolism of the avalglucosidase alfa. The protein portion of the drug however does break down into small peptides via catabolic pathways. [10] The clearance of the drug is 0.9 L/hour in patients that exhibited late-stage Pompe disease.[10]

    Society and culture

    In July 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Nexviadyme, intended for the treatment of glycogen storage disease type II (Pompe disease).[11] The applicant for this medicinal product is Genzyme Europe BV.[11] In August 2021, Genzyme Europe BV requested a re-examination.[11] Avalglucosidase alfa was approved for medical use in the European Union in June 2022.[1]

    The U.S. Food and Drug Administration (FDA) granted the application for avalglucosidase alfa fast track, priority review, breakthrough therapy, and orphan drug designations.[7] The FDA granted the approval of Nexviazyme to Genzyme Corporation.[7]

    Names

    Avalglucosidase alfa is the international nonproprietary name (INN).[12]

    References

    1. 1 2 3 4 5 6 7 8 9 "Nexviadyme EPAR". European Medicines Agency (EMA). 20 July 2021. Archived from the original on 28 July 2022. Retrieved 29 July 2022. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
    2. 1 2 3 4 5 6 7 8 9 10 11 12 "Nexviazyme ngpt- avalglucosidase alfa injection, powder, lyophilized, for solution". DailyMed. Archived from the original on 12 August 2021. Retrieved 11 August 2021.
    3. 1 2 "Nexviazyme". Therapeutic Goods Administration (TGA). 1 November 2021. Archived from the original on 28 December 2021. Retrieved 28 December 2021.
    4. ↑ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Archived from the original on 3 April 2022. Retrieved 13 May 2022.
    5. ↑ "Notice: Multiple Additions to the Prescription Drug List (PDL) [2022-01-24]". Health Canada. 24 January 2022. Archived from the original on 29 May 2022. Retrieved 28 May 2022.
    6. ↑ "Summary Basis of Decision (SBD) for Nexviazyme". Health Canada. 23 October 2014. Archived from the original on 29 May 2022. Retrieved 29 May 2022.
    7. 1 2 3 4 5 "FDA Approves New Treatment for Pompe Disease". U.S. Food and Drug Administration (FDA) (Press release). 6 August 2021. Archived from the original on 6 August 2021. Retrieved 6 August 2021. Public Domain This article incorporates text from this source, which is in the public domain.
    8. ↑ "Avalglucosidase alfa". SPS - Specialist Pharmacy Service. 5 April 2017. Archived from the original on 3 October 2021. Retrieved 28 October 2022.
    9. ↑ "Avalglucosidase Alfa (Nexviazyme)". Canadian Journal of Health Technologies. 21 July 2022. doi:10.51731/cjht.2022.402. Archived from the original on 4 August 2022. Retrieved 28 October 2022.
    10. 1 2 3 4 5 6 7 8 9 "Avalglucosidase alfa". go.drugbank.com. Archived from the original on 15 June 2022. Retrieved 2022-06-15.
    11. 1 2 3 "Nexviadyme: Pending EC decision". European Medicines Agency (EMA). 23 July 2021. Archived from the original on 28 July 2021. Retrieved 27 July 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
    12. ↑ World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 79". WHO Drug Information. 32 (1): 95–6. hdl:10665/330941.
    Identifiers:


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