|Trade names||Nexviazyme, Nexviadyme|
|Other names||GZ-402666, avalglucosidase alfa-ngpt|
|Main uses||Glycogen storage disease type II (Pompe disease)|
|Side effects||Headache, tiredness, diarrhea, nausea, joint pain, dizziness, muscle pain, itchiness, shortness of breath, skin redness|
|Typical dose||20-40 mg/kg q 2 weeks|
|Chemical and physical data|
|Molar mass||99376.93 g·mol−1|
Avalglucosidase alfa, sold under the brand name Nexviazyme, is a medication used to treat glycogen storage disease type II (Pompe disease). It is used in those over the age of one with late onset disease. It is given gradually into a vein every two weeks.
Common side effects include headache, tiredness, diarrhea, nausea, joint pain, dizziness, muscle pain, itchiness, shortness of breath, and skin redness. Other side effects may include anaphylaxis, infusion reaction, and cardiorespiratory failure. It is an enzyme replacement therapy, specifically to replace alpha-glucosidase. It is a hydrolytic lysosomal glycogen-specific enzyme.
Avalglucosidase alfa was approved for medical use in the United States in 2021 and Europe in 2022. It costs about 900 USD per 50-mg in the United States as of 2021. In Canada it costs about 525,000 CAD per person per year as of 2022.
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). It appears to be at least as effective as alglucosidase alfa.
Avalglucosidase alfa has a blackbox warning for hypersensitivity, infusion-related reactions, and cardiorespiratory failure.
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.
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. The bis-MGP of avalglucosidase alpha binds to the cation-independent mannose-6-phosphate receptor which is located on the skeletal muscles. Once the molecule binds to the receptor, the drug enters the cell. The drug then enters the lysosomes of the cell. Within the lysosome of the cell, the drugs undergoes cleavage proteolytically and then acts as an enzyme.
The volume of distribution of avalglucosidase alfa was 3.4 L in patients who had Pompe disease of a late onset. The average half-life of avalglucosidase alfa was 1.6 hours, measured in patients with late stage Pompe disease. 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.  The clearance of the drug is 0.9 L/hour in patients that exhibited late-stage Pompe disease.
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). The applicant for this medicinal product is Genzyme Europe BV. In August 2021, Genzyme Europe BV requested a re-examination. Avalglucosidase alfa was approved for medical use in the European Union in June 2022.
The U.S. Food and Drug Administration (FDA) granted the application for avalglucosidase alfa fast track, priority review, breakthrough therapy, and orphan drug designations. The FDA granted the approval of Nexviazyme to Genzyme Corporation.
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