Avalglucosidase alfa

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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

Legal status

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. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "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. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 "Nexviazyme ngpt- avalglucosidase alfa injection, powder, lyophilized, for solution". DailyMed. Archived from the original on 12 August 2021. Retrieved 11 August 2021.
  3. 3.0 3.1 "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. 7.0 7.1 7.2 7.3 7.4 "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. 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 10.8 "Avalglucosidase alfa". go.drugbank.com. Archived from the original on 15 June 2022. Retrieved 2022-06-15.
  11. 11.0 11.1 11.2 "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.

External links

Identifiers: