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Avalglucosidase alfa

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Not to be confused with Alglucosidase alfa.

Avalglucosidase alfa
Clinical data
Trade namesNexviazyme, Nexviadyme
Other namesGZ-402666, avalglucosidase alfa-ngpt
License data
Pregnancy
category
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
FormulaC4490H6818N1197O1299S32
Molar mass99376.93 g·mol−1

Avalglucosidase alfa, sold under the brand name Nexviazyme, is an enzyme replacement therapy medication used for the treatment of glycogen storage disease type II (Pompe disease).[6][7]

The most common side effects include headache, fatigue, diarrhea, nausea, joint pain (arthralgia), dizziness, muscle pain (myalgia), itching (pruritus), vomiting, difficulty breathing (dyspnea), skin redness (erythema), feeling of "pins and needles" (paresthesia) and skin welts (urticaria).[7]

Avalglucosidase alfa was approved for medical use in the United States in August 2021,[7][9][10][11] and in the European Union in June 2022.[8]

Medical uses

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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 indicated for the treatment of people aged one year and older with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency).[6][7]

Mechanism of action

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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.[12] The bis-MGP of avalglucosidase alpha binds to the cation-independent mannose-6-phosphate receptor which is located on the skeletal muscles.[12] Once the molecule binds to the receptor, the drug enters the cell. The drug then enters the lysosomes of the cell.[12] Within the lysosome of the cell, the drugs undergoes cleavage proteolytically and then acts as an enzyme.[12]

Pharmacokinetics

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The volume of distribution of avalglucosidase alfa was 3.4 L in patients who had Pompe disease of a late onset.[12] The average half-life of avalglucosidase alfa was 1.6 hours, measured in patients with late stage Pompe disease.[12] There is little information available on the metabolism of the avalglucosidase alfa. The protein portion of the drug however does break down into small peptides via catabolic pathways.[12] The clearance of the drug is 0.9 L/hour in patients that exhibited late-stage Pompe disease.[12]

Blackbox warnings

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Avalglucosidase alfa has a blackbox warning for hypersensitivity, infusion-related reactions, and cardiorespiratory failure.[12]

History

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Avalglucosidase alfa's safety data was obtained from four clinical trials (trial 1/NCT02782741, trial 2/NCT01898364, trial 3/NCT02032524, trial 4/NCT03019406).[9] These trials enrolled 124 participants with late-onset Pompe disease and 22 participants with infantile-onset Pompe disease.[9] The participants were from 22 countries around the world, including the United States.[9] Avalglucosidase alfa was evaluated in four trials of 146 participants with Pompe disease.[9] Trial 1 evaluated the benefits and side effects of avalglucosidase alfa, and all four trials evaluated the side effects of avalglucosidase alfa.[9] In trial 1, participants received either avalglucosidase alfa or another drug (called the active comparator) intravenously once every two weeks for 49 weeks.[9] Neither the participants nor the healthcare providers knew which treatment was being given until after week 49.[9] Participants in this trial were followed for up to five years.[9] The benefit of avalglucosidase alfa was evaluated by comparing the change in lung function and distance walked between participants who received avalglucosidase alfa to the change in participants who were treated with the active comparator.[9]

Society and culture

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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).[13] The applicant for this medicinal product is Genzyme Europe BV.[13] In August 2021, Genzyme Europe BV requested a re-examination.[13] Avalglucosidase alfa was approved for medical use in the European Union in June 2022.[8][14]

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][15] The FDA granted the approval of Nexviazyme to Genzyme Corporation.[7]

Names

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Avalglucosidase alfa is the international nonproprietary name (INN).[16]

References

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  1. ^ a b "Nexviazyme". Therapeutic Goods Administration (TGA). 1 November 2021. Archived from the original on 28 December 2021. Retrieved 28 December 2021.
  2. ^ "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.
  3. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  4. ^ "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.
  5. ^ "Summary Basis of Decision (SBD) for Nexviazyme". Health Canada. 23 October 2014. Archived from the original on 29 May 2022. Retrieved 29 May 2022.
  6. ^ a b c "Nexviazyme ngpt- avalglucosidase alfa injection, powder, lyophilized, for solution". DailyMed. Archived from the original on 12 August 2021. Retrieved 11 August 2021.
  7. ^ a b c d e f g h "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. ^ a b c "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 copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  9. ^ a b c d e f g h i j "Drug Trials Snapshot: Nexviazyme". U.S. Food and Drug Administration (FDA). 30 May 2023. Retrieved 1 June 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  10. ^ "FDA approves Nexviazyme (avalglucosidase alfa-ngpt), an important new treatment option for late-onset Pompe disease" (Press release). Sanofi. 6 August 2021. Archived from the original on 6 August 2021. Retrieved 6 August 2021 – via GlobeNewswire.
  11. ^ "Drug Approval Package: Nexviazyme". U.S. Food and Drug Administration (FDA). 7 September 2021. Archived from the original on 29 January 2023. Retrieved 1 June 2023.
  12. ^ a b c d e f g h i "Avalglucosidase alfa". go.drugbank.com. Archived from the original on 15 June 2022. Retrieved 15 June 2022.
  13. ^ a b c "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 copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  14. ^ "Nexviadyme Product information". Union Register of medicinal products. Archived from the original on 4 March 2023. Retrieved 3 March 2023.
  15. ^ Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original on 6 December 2022. Retrieved 22 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  16. ^ 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.
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  • Clinical trial number NCT02782741 for "Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies Avalglucosidase Alfa and Alglucosidase Alfa Administered Every Other Week in Patients With Late-onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease (COMET)" at ClinicalTrials.gov
  • Clinical trial number NCT01898364 for "Safety and Efficacy Evaluation of Repeat neoGAA Dosing in Late Onset Pompe Disease Patients" at ClinicalTrials.gov
  • Clinical trial number NCT02032524 for "Avalglucosidase Alfa Extension Study (NEO-EXT)" at ClinicalTrials.gov
  • Clinical trial number NCT03019406 for "A Study to Assess Safety and Efficacy of Avalglucosidase Alfa Administered Every Other Week in Pediatric Patients With Infantile-onset Pompe Disease Previously Treated With Alglucosidase Alfa (Mini-COMET)" at ClinicalTrials.gov
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