Avalglucosidase alfa
| Clinical data | |
|---|---|
| Trade names | Nexviazyme, Nexviadyme |
| Other names | GZ-402666, avalglucosidase alfa-ngpt |
| License data | |
| Pregnancy category | |
| Routes of administration | Intravenous |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
| CAS Number | |
| DrugBank | |
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| KEGG | |
| Chemical and physical data | |
| Formula | C4490H6818N1197O1299S32 |
| Molar mass | 99376.93 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]
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 was approved for medical use in the United States in August 2021,[7][9][10] and in the European Union in June 2022.[8]
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).[6][7]
Mechanism of action
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.[11] The bis-MGP of avalglucosidase alpha binds to the cation-independent mannose-6-phosphate receptor which is located on the skeletal muscles.[11] Once the molecule binds to the receptor, the drug enters the cell. The drug then enters the lysosomes of the cell.[11] Within the lysosome of the cell, the drugs undergoes cleavage proteolytically and then acts as an enzyme.[11]
Pharmacokinetics
The volume of distribution of avalglucosidase alfa was 3.4 L in patients who had Pompe disease of a late onset.[11] The average half-life of avalglucosidase alfa was 1.6 hours, measured in patients with late stage Pompe disease.[11] 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. [11] The clearance of the drug is 0.9 L/hour in patients that exhibited late-stage Pompe disease.[11]
Blackbox warnings
Avalglucosidase alfa has a blackbox warning for hypersensitivity, infusion-related reactions, and cardiorespiratory failure.[11]
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).[12] The applicant for this medicinal product is Genzyme Europe BV.[12] In August 2021, Genzyme Europe BV requested a re-examination.[12] Avalglucosidase alfa was approved for medical use in the European Union in June 2022.[8]
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).[13]
References
- ^ a b "Nexviazyme". Therapeutic Goods Administration (TGA). 1 November 2021. Archived from the original on 28 December 2021. Retrieved 28 December 2021.
- ^ "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.
- ^ "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.
- ^ "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.
- ^ "Summary Basis of Decision (SBD) for Nexviazyme". Health Canada. 23 October 2014. Archived from the original on 29 May 2022. Retrieved 29 May 2022.
- ^ 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.
- ^ 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.
This article incorporates text from this source, which is in the public domain.
- ^ 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 © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ^ "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.
- ^ "Nexviazyme: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 10 August 2021. Retrieved 9 August 2021.
- ^ 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.
- ^ 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 © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ^ 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
- "Avalglucosidase alfa". Drug Information Portal. U.S. National Library of Medicine.
