Nexviazyme

About Avalglucosidase alfa-ngpt

• Avalglucosidase alfa, marketed under the brand name Nexviazyme. 
• The U.S. Food and Drug Administration (FDA) approved Nexviazyme (avalglucosidase alfa-ngpt) for the treatment of late-onset Pompe disease on August 6, 2021.
• Nexviazyme is a lysosomal enzyme that specifically targets glycogen hydrolysis, designed for treating individuals aged 1 year and diagnosed with late-onset Pompe disease, characterized by deficiency in lysosomal acid alpha-glucosidase (GAA).
• Avalglucosidase alfa comprises human GAA enzyme linked to bis-mannose-6-phosphate (bis-M6P) glycans. 
• These glycans bind to mannose-6-phosphate receptors on skeletal muscles, facilitating cellular uptake and transport to lysosomes. 
• Within lysosomes, the drug undergoes proteolytic cleavage and acts enzymatically to break down glycogen. This mechanism is pivotal in treating conditions like Pompe disease.
• Avalglucosidase alfa has a volume of distribution of 3.4 L and an average half-life of 1.6 hours in late-stage Pompe disease patients. 
• Its metabolism involves the breakdown of the protein component into small peptides, while its clearance is reported at 0.9 L/hour in late-stage Pompe disease patients.

Strength: 

The medication is provided in the form of a single-dose vial containing Nexviazyme 100 mg  solution for intravenous injection.

Recommended Dosage:

Before administering the Nexviazyme injection, consider pretreatment with antihistamines, antipyretics, and/or corticosteroids. This medicine should be reconstituted and diluted before use according to the instructions in the Dosage and Administration section.

Nexviazyme infusion is given as an intravenous. For patients weighing:

• 30 kg or more, the recommended dosage is 20 mg/kg of actual body weight every two weeks.
• Less than 30 kg, the recommended dosage is 40 mg/kg of actual body weight every two weeks.
• The initial recommended infusion rate is 1 mg/kg/hour. The infusion rate can be gradually increased every 30 minutes if there are no signs of infusion-associated reactions (IARs).

Important:

Calculate the required number of vials based on the patient’s weight and prescribed dose. Allow the vials to reach room temperature for 30 minutes before reconstitution. Slowly add 10 mL of Sterile Water for Injection, USP, to each vial, gently tilting and rolling to dissolve the powder. Inspect the solution for clarity and color immediately, avoiding use if any particles or discoloration are present.

After dilution, the solution should be refrigerated at a temperature between 36°F to 46°F (2°C to 8°C) for up to 24 hours, avoiding freezing. It should be completely infused within 9 hours after removal from the refrigerator. Once removed from the refrigerator, the solution should not be refrigerated again. If the solution has been refrigerated for more than 24 hours or cannot be infused completely within 9 hours after removal from the refrigerator, it should be discarded.

Warnings & Precautions

• In case of severe hypersensitivity reactions, including anaphylaxis, discontinue Nexviazyme immediately and provide necessary medical support, including cardiopulmonary resuscitation equipment. 
• Similarly, if severe infusion-associated reactions (IARs) occur, consider discontinuation of the medicine and initiate appropriate medical treatment promptly. 
• Patients prone to fluid volume overload or with acute underlying respiratory illness or compromised cardiac/respiratory function may experience exacerbation of their condition during Nexviazyme infusion, warranting careful monitoring.

Common Nexviazyme Side Effects:

• Headache
• Fatigue
• Diarrhea
• Nausea
• Arthralgia
• Dizziness
• Myalgia
• Pruritus
• Vomiting
• Dyspnea
• Erythema
• Paresthesia
• Urticaria

Use in Specific Population

• Insufficient data from case reports exist to assess the risk of major birth defects, miscarriage, or adverse maternal and fetal outcomes associated with Nexviazyme use during pregnancy. 
• Untreated Pompe disease may worsen respiratory and musculoskeletal symptoms in pregnant individuals.
•  No information is available regarding avalglucosidase alfa-ngpt in human or animal milk, its effects on breastfed infants, or its impact on milk production. 
• While the safety and efficacy of Nexviazyme for late-onset Pompe disease have been established in pediatric patients aged 1 year and older, it is not approved for infantile-onset Pompe disease. 
• Clinical studies included a limited number of patients aged 65 and older, with the recommended dosage being the same as for younger adults.

Storage and Handling

• Store vials of Nexviazyme in the refrigerator at temperatures between 36°F and 46°F (2°C and 8°C). 
• Ensure not to use the medicine past the expiration date indicated on the vial.
• Do not freeze the medicine. 
• Keep the medicine away from pets and children.