NEXVIAZYME (avalglucosidase alfa-ngpt) for injection

NEXVIAZYME (avalglucosidase alfa-ngpt) for injection

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NEXVIAZYME (avalglucosidase alfa-ngpt) for injection

Avalglucosidase alfa-ngpt is a hydrolytic lysosomal glycogen-specific recombinant human αglucosidase enzyme conjugated with multiple synthetic bis-mannose-6-phosphate (bis-M6P)­ tetra-mannose glycans resulting in approximately 15 moles of M6P per mole of enzyme (15 M6P) and is produced in Chinese hamster ovary cells (CHO). Avalglucosidase alfa-ngpt has a molecular weight of approximately 124 kDa.

NEXVIAZYME (avalglucosidase alfa-ngpt) for injection is a sterile white to pale-yellow lyophilized powder for intravenous use after reconstitution and dilution. Each single-dose vial contains 100 mg of avalglucosidase alfa-ngpt, glycine (200 mg), L-Histidine (10.7 mg), LHistidine HCl monohydrate (6.5 mg), mannitol (200 mg), and polysorbate 80 (1 mg). After reconstitution with 10 mL of Sterile Water for Injection, USP, the resultant concentration is 100 mg/10 mL (10 mg/mL) with a pH of approximately 6.2.

Indications and usage

NEXVIAZYME is a hydrolytic lysosomal glycogen-specific enzyme indicated for the treatment of patients 1 year of age and older with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency)

Mechanism of Action

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.

Recommended Dosage and Administration

  • Prior to NEXVIAZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids
  • NEXVIAZYME must be reconstituted and diluted prior to use

NEXVIAZYME is administered as intravenous infusion. For patients weighing:

  • ≥30 kg, the recommended dosage is 20 mg/kg (of actual body weight) every two weeks
  • <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. Gradually increase the infusion rate every 30 minutes if there are no signs of infusion-associated reactions (IARs)

Warnings and precautions

Hypersensitivity Reactions Including Anaphylaxis: Prior to NEXVIAZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during NEXVIAZYME administration.

  • If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, NEXVIAZYME should be discontinued immediately and appropriate medical treatment should be initiated. The risks and benefits of readministering NEXVIAZYME following severe hypersensitivity reaction (including anaphylaxis) should be considered.
  • If a mild or moderate hypersensitivity reaction occurs, the infusion rate may be slowed or temporarily stopped.

Anaphylaxis signs and symptoms included respiratory distress, chest discomfort, flushing, cough, erythema, lip swelling, pruritus, swollen tongue, dysphagia, and rash. Symptoms of severe hypersensitivity reactions included respiratory distress, erythema, urticaria, tongue edema, and rash. Increased incidence of hypersensitivity reactions was observed in patients with higher antidrug antibody (ADA) titers

Infusion-Associated Reactions: Antihistamines, antipyretics, and/or corticosteroids can be given prior to NEXVIAZYME administration to reduce the risk of infusion-associated reactions (IARs). However, IARs may still occur in patients after receiving pretreatment.

  • If severe IARs occur, consider immediate discontinuation of NEXVIAZYME, initiation of appropriate medical treatment, and the benefits and risks of readministering NEXVIAZYME following severe IARs. Some patients have been rechallenged using slower infusion rates at a dose lower than the recommended dose. Once a patient tolerates the infusion, the dose may be increased to reach the recommended approved dose.
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  • If mild or moderate IARs occur regardless of pretreatment, decreasing the infusion rate or temporarily stopping the infusion may ameliorate the symptoms.

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 for whom fluid restriction is indicated may be at risk of serious exacerbation of their cardiac or respiratory status during the NEXVIAZYME infusion. More frequent monitoring of vitals should be performed during NEXVIAZYME infusion in these patients. Some patients may require prolonged observation times.

Adverse reactions

The most common adverse reactions (>5%) were headache, fatigue, diarrhea, nausea, arthralgia, dizziness, myalgia, pruritus, vomiting, dyspnea, erythema, paresthesia and urticaria.

Use in specific populations

Pregnancy

Available data from case reports of NEXVIAZYME use in pregnant women are insufficient to evaluate for a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, available data from postmarketing reports and published case reports on alglucosidase alfa (another hydrolytic lysosomal glycogen-specific enzyme replacement therapy) use in pregnant women have not identified a drug-associated risk of adverse pregnancy outcomes. The continuation of treatment for Pompe disease during pregnancy should be individualized to the pregnant woman. Untreated Pompe disease may result in worsening disease symptoms in pregnant women

Lactation

There are no data on the presence of avalglucosidase alfa-ngpt in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Available published literature suggests the presence of alglucosidase alfa (another hydrolytic lysosomal glycogen-specific enzyme replacement therapy) in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for NEXVIAZYME and any potential adverse effects on the breastfed child from NEXVIAZYME or from the underlying maternal condition.

Pediatric Use: The safety and effectiveness of NEXVIAZYME for the treatment of late-onset Pompe disease have been established in pediatric patients 1 year of age and older. Use of NEXVIAZYME for this indication is supported by evidence from two clinical studies which included adults with LOPD, and 1 pediatric patient with LOPD (16 years of age) and from safety experience in 19 pediatric patients with infantile-onset Pompe disease (IOPD) (1 to 12 years of age) treated with NEXVIAZYME. NEXVIAZYME is not approved for the treatment of IOPD.

The safety profile of NEXVIAZYME in pediatric patients 1 to 12 years old with Pompe disease was similar to the safety profile of NEXVIAZYME in older pediatric and adult patients with LOPD. The safety and effectiveness of NEXVIAZYME have not been established in pediatric patients younger than 1 year of age.

Geriatric Use: Clinical studies with NEXVIAZYME included 14 patients 65 to 74 years of age and 3 patients 75 years of age and older. The recommended dosage in geriatric patients is the same as the recommended dosage in younger adult patients

Storage

Refrigerate vials of NEXVIAZYME at 36°F to 46°F (2°C to 8°C ). Do not use NEXVIAZYME after the expiration date on the vial.

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