General Information

Nexviazyme (avalglucosidase alfa-ngpt) is a hydrolytic lysosomal glycogen-specific enzyme.

Nexviazyme is specifically indicated for the treatment of patients 1 year of age and older with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency).

Nexviazyme is supplied as a solution for intravenous administration. Prior to Nexviazyme administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Nexviazyme must be reconstituted and diluted prior to use. The recommended dosing/administration is as follows:

For patients weighing:

• ≥30 kg, the recommended dosage is 20 mg/kg (of actual body weight) every two weeks. 
  • Initial and Subsequent Infusions: The recommended starting infusion rate is 1 mg/kg/hour. If there are no signs of infusion-associated reactions (IARs), gradually increase the infusion rate every 30 minutes in each of the following three steps: 3 mg/kg/hour, 5 mg/kg/hour, and then 7 mg/kg/hour; then, maintain the infusion rate at 7 mg/kg/hour until the infusion is complete. The approximate total infusion duration is 4 hours to 5 hours.
• <30 kg, the recommended dosage is 40 mg/kg (of actual body weight) every two weeks.
  • Initial Infusion: The recommended starting infusion rate is 1 mg/kg/hour. If there are no signs of IARs, gradually increase the infusion rate every 30 minutes in each of the following three steps: 3 mg/kg/hour, 5 mg/kg/hour, and then 7 mg/kg/hour; then, maintain the infusion rate at 7 mg/kg/hour until the infusion is complete (4-step process). The approximate total infusion duration is 7 hours.
  • Subsequent Infusions: The recommended starting infusion rate is 1 mg/kg/hour, with gradual increase in infusion rate every 30 minutes if there are no signs of IARs. The process may use either the above 4-step process or the following 5-step process: 3 mg/kg/hour, 6 mg/kg/hour, 8 mg/kg/hour, and then 10 mg/kg/hour; then, maintain the infusion rate at 10 mg/kg/hour until the infusion is complete. The approximate total 5-step infusion duration is 5 hours.

Mechanism of Action

Nexviazyme (avalglucosidase alfa-ngpt) is a hydrolytic lysosomal glycogen-specific enzyme. Pompe disease (also known as glycogen storage disease type II, acid maltase deficiency, and glycogenosis type II) is an inherited disorder of glycogen metabolism caused by a deficiency of the lysosomal enzyme acid α-glucosidase (GAA), which results in intralysosomal accumulation of glycogen in various tissues. Avalglucosidase alfa-ngpt provides an exogenous source of GAA. The M6P on avalglucosidase alfa-ngpt mediates binding to M6P receptors on the cell surface with high affinity. After binding, it is internalized and transported into lysosomes where it undergoes proteolytic cleavage that results in increased GAA enzymatic activity. Avalglucosidase alfa-ngpt then exerts enzymatic activity in cleaving glycogen.

Side Effects

Adverse effects associated with the use of Nexviazyme may include, but are not limited to, the following:

• headache
• fatigue
• diarrhea
• nausea
• arthralgia
• dizziness
• myalgia
• pruritus
• vomiting
• dyspnea
• erythema
• paresthesia
• urticaria

The Nexviazyme drug label comes with the following Black Box Warning: Hypersensitivity Reactions Including Anaphylaxis: Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available. If a severe hypersensitivity reaction occurs, Nexviazyme should be discontinued immediately and appropriate medical treatment should be initiated. Infusion-Associated Reactions (IARs): If severe IARs occur, consider immediate discontinuation and initiation of appropriate medical treatment. Risk of Acute Cardiorespiratory Failure in Susceptible Patients: Patients susceptible to fluid volume overload, or those with acute underlying respiratory illness or compromised cardiac or respiratory function, may be at risk of serious exacerbation of their cardiac or respiratory status during Nexviazyme infusion.

Clinical Trial Results

The FDA Approval of Nexviazyme was based on the pivotal Phase 3 COMET trial. The randomized, double-blinded, multinational, multicenter trial compared the efficacy and safety of Nexviazyme to alglucosidase alfa in 100 treatment-naive patients. Patients were randomized in a 1:1 ratio based on baseline forced vital capacity (FVC), gender, age, and country to receive 20 mg/kg of Nexviazyme or alglucosidase alfa administered intravenously once every two weeks for 49 weeks. When compared to baseline, patients treated with Nexviazyme had a 2.9-point improvement (SE=0.9) in forced vital capacity (FVC) percent-predicted at Week 49, the study’s primary endpoint. Patients treated with Nexviazyme had a 2.4-point greater improvement in FVC percent-predicted compared to patients treated with alglucosidase alfa at Week 49 meeting the measurement of non-inferiority. Statistical superiority of Nexviazyme over alglucosidase alfa was not achieved. A key secondary endpoint in the trial measured functional endurance with the 6-minute walk test (6MWT). When compared to baseline, patients treated with Nexviazyme walked 32.2 meters farther (SE=9.9) at Week 49. Patients treated with Nexviazyme walked 30 meters farther than patients treated with alglucosidase alfa at Week 49.