Avalglucosidase alfa

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).

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).

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 was approved for medical use in the United States in August 2021, and in the European Union in June 2022.

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).

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. 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.

Pharmacokinetics

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 available 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.

Blackbox warnings

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

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). 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.

Names

Avalglucosidase alfa is the international nonproprietary name (INN).

External links

• "Avalglucosidase alfa". Drug Information Portal. U.S. National Library of Medicine.