Avalglucosidase Alfa-ngpt (Monograph)

Brand name: Nexviazyme [Web]
Drug class: Enzymes

Medically reviewed by Drugs.com on Dec 11, 2023. Written by ASHP.

Warning

Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available. If a severe hypersensitivity reaction occurs, avalglucosidase alfa-ngpt should be discontinued immediately and appropriate medical treatment initiated.

If severe IARs occur, consider immediate discontinuation and initiation of appropriate medical treatment.

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 avalglucosidase alfa-ngpt infusion.

Introduction

Hydrolytic lysosomal glycogen-specific recombinant human α-glucosidase (GAA) enzyme.

Uses for Avalglucosidase Alfa-ngpt

Pompe Disease

Treatment of patients ≥1 year of age with late-onset Pompe disease (LOPD) (lysosomal acid alpha-glucosidase [GAA] deficiency).

Designated an orphan drug by FDA for this indication.

Pompe disease is caused by a deficiency of glycogen-degrading lysosomal enzyme GAA. Enzyme replacement therapy with alglucosidase alfa has been the standard of care for patients with Pompe disease. Avalglucosidase alfa is a next-generation recombinant human GAA enzyme replacement therapy that has been specifically designed to enhance targeting of mannose-6-phosphate (M6P) receptor-mediated uptake, an essential pathway for cellular uptake and lysosomal trafficking.

Avalglucosidase Alfa-ngpt Dosage and Administration

General

Patient Monitoring

Monitor for hypersensitivity reactions, including anaphylaxis, in addition to infusion-associated reactions (IARs).
Monitor vital signs more frequently in patients who are susceptible to fluid volume overload, or those in whom fluid restriction is indicated with acute underlying respiratory illness or compromised cardiac or respiratory function during avalglucosidase alfa-ngpt administration. Prolonged observation periods after infusion may also be required.

Premedication and Prophylaxis

Consider administering antihistamines, antipyretics, and/or corticosteroids as pretreatment to reduce the risk of infusion-associated reactions (IARs).

Dispensing and Administration Precautions

Ensure appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, are available during administration.

Administration

IV Administration

Administer as an IV infusion. It is recommended to use a sterile, low-protein binding, in-line, 0.2 micron filter to administer the drug.

Commercially available as a lyophilized powder that must be reconstituted and further diluted before IV administration.

To ensure full delivery of the dose, flush infusion line with 5% dextrose injection at the end of the infusion. Do not infuse the diluted solution in the same IV line with other products.

Reconstitution

Prior to reconstitution, remove the required number of vials from the refrigerator and allow to sit to reach room temperature for approximately 30 minutes.

Reconstitute each vial with 10 mL of sterile water for injection by slow drop-wise addition of the diluent down the inside of vial and not directly onto lyophilized powder. Do not forcefully inject diluent directly into lyophilized powder to avoid foaming.

Tilt and roll each vial gently until the solution is dissolved; do not invert, swirl, or shake.

After reconstitution, each vial will yield a concentration of 100 mg/10 mL (10 mg/mL) of avalglucosidase alfa-ngpt.

Dilution

Slowly add reconstituted solution to infusion bag containing 5% dextrose injection. Recommended total infusion volume is weight-dependent. See Table 1 for the recommended infusion volume. Avoid foaming or agitation of the infusion bag, and avoid introducing air into the infusion bag. Mix the contents of the infusion bag by gently inverting or massaging the bag; do not shake. After dilution, the final solution concentration ranges from 0.5-4 mg/mL of avalglucosidase alfa-ngpt.

Table 1. Total Intravenous Infusion Volume for Avalglucosidase alfa-ngpt Based on Patient Weight1
Patient Weight (kg)	Total Infusion Volume (mL) Based on 20 mg/kg Dose	Total Infusion Volume (mL) Based on 40 mg/kg Dose
5-9.9	N/A	100
10-19.9	N/A	200
20-29.9	N/A	300
30-34.9	200	N/A
35-49.9	250	N/A
50-59.9	300	N/A
60-99.9	500	N/A
100-119.9	600	N/A
120-140	700	N/A

Rate of Administration

Regardless of dosage, administer all avalglucosidase alfa-ngpt infusions at an initial rate of 1 mg/kg/hour. May be gradually increased every 30 minutes based on patient comfort and if no signs of infusion-associated reactions (IARs). Total recommended infusion duration between 4–7 hours.

Patients Receiving Recommended Dosage of 20 mg/kg: Start initial and subsequent infusions at rate of 1 mg/kg/hour; if no signs of IARs, gradually increase rate every 30 minutes in each of the following 3 steps: 3 mg/kg/hour, 5 mg/kg/hour, then 7 mg/kg/hour; maintain the infusion rate at 7 mg/kg/hour until infusion completion. Total approximate infusion duration 4–5 hours.

Patients Receiving Recommended Dosage of 40 mg/kg: Start initial infusions at rate of 1 mg/kg/hour; if no signs of IARs, gradually increase rate every 30 minutes in each of the following 3 steps: 3 mg/kg/hour, 5 mg/kg/hour, then 7 mg/kg/hour; then, maintain the infusion rate at 7 mg/kg/hour until infusion completion. Total approximate infusion duration of 7 hours. Start subsequent infusions at rate of 1 mg/kg/hour; if no signs of IARs, gradually increase rate every 30 minutes using the above 4-step process, or the following 5-step process: 3 mg/kg/hour, 6 mg/kg/hour, 8 mg/kg/hour, then 10 mg/kg/hour; maintain the infusion rate at 10 mg/kg/hour until infusion completion. Total approximate infusion duration of 5 hours.

Dosage

Pediatric Patients

Pompe Disease

IV

For pediatric patients ≥1 year of age weighing <30 kg, the recommended dosage of avalglucosidase alfa-ngpt is 40 mg/kg (of actual body weight) every 2 weeks.

For pediatric patients ≥1 year of age weighing ≥30 kg, the recommended dosage of avalglucosidase alfa-ngpt is 20 mg/kg (of actual body weight) every 2 weeks.

If one or more doses are missed, restart treatment as soon as possible, maintaining the 2 week interval between infusions thereafter.

Adults

Pompe Disease

IV

For adults weighing <30 kg, the recommended dosage is 40 mg/kg (of actual body weight) every 2 weeks.

For adults weighing ≥30 kg, the recommended dosage is 20 mg/kg (of actual body weight) every 2 weeks.

If one or more doses are missed, restart treatment as soon as possible, maintaining the 2 week interval between infusions thereafter.

Dosage Modification for Toxicity

Severe hypersensitivity reaction (including anaphylaxis) or severe IAR during infusion: Immediately discontinue; administer appropriate medical treatment.

Mild to moderate hypersensitivity reaction, or moderate IAR during infusion: Interrupt or slow infusion rate; initiate appropriate medical treatment. If symptoms persist, wait ≥30 minutes for symptom resolution before stopping. If symptoms subside, may resume at half the rate at which reaction occurred for 30 minutes, then subsequently increase by 50% for an additional 15–30 minutes. If no symptom recurrence, may increase infusion to rate at which reaction occurred. Consider further rate increases in a stepwise manner.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Use

No dosage adjustments necessary.

Cautions for Avalglucosidase Alfa-ngpt

Contraindications

None.

Warnings/Precautions

Hypersensitivity Reactions

Life-threatening hypersensitivity reactions, including anaphylaxis, reported (see Boxed Warning). Symptoms included respiratory distress, chest discomfort, erythema, generalized edema, hypotension, hypoxia, rash, tongue edema, and urticaria.

Consider pretreatmeant with antihistamines, antipyretics, and/or corticosteroids prior to infusion. Ensure appropriate medical support measures, including cardiopulmonary resuscitation equipment, are available during administration.

If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue avalglucosidase alfa-ngpt immediately and initiate appropriate medical treatment.

Consider risks and benefits of readministration following severe hypersensitivity reactions, including anaphylaxis. May rechallenge using slower infusion rate at a dosage lower than the recommended dosage.

In patients who experience severe hypersensitivity reaction, consider desensitization procedure. If readministering avalglucosidase alfa-ngpt, ensure patient tolerates the infusion. If tolerated, may increase the dosage (dose and/or the rate) to reach the recommended dosage.

Slow or temporarily interrupt the infusion if a mild or moderate hypersensitivity reaction occurs.

Infusion-associated Reactions (IARs)

IARs reported; occurred at any time during and/or within a few hours after infusion and were more likely to occur with higher infusion rates. Reactions included chest discomfort, nausea, dysphagia, erythema, respiratory distress, tongue edema, urticaria, and increased BP (see Boxed Warning.).

Patients with acute underlying illness at the time of infusion may be at greater risk for IARs. Advanced Pompe disease with compromised cardiac and respiratory function may further increase risk of severe complications.

May administer antihistamines, antipyretics, and/or corticosteroids prior to infusion to reduce risk.

If severe IARs occur, consider immediate discontinuation of infusion and initiation of appropriate medical treatment. Consider benefits and risks of readministration following severe IARs. May rechallenge using slower infusion rates at a dose lower than the recommended dose. Once tolerated, the dosage may be further increased to reach the recommended dosage.

If mild or moderate IARs occur, decrease the infusion rate or temporarily stop infusion.

Acute Cardiorespiratory Failure

Risk of cardiac or respiratory exacerbation in 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 (see Boxed Warning).

Monitor vitals more frequently during infusion in these patients; some patients may require prolonged observation.

Specific Populations

Pregnancy

Data insufficient to evaluate for a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Drug-associated risk of adverse pregnancy outcomes not identifed with alglucosidase-alfa, another enzyme replacement therapy.

Continuation of treatment for Pompe disease during pregnancy should be individualized; untreated disease may result in worsening symptoms in pregnant women.

Pregnant women exposed to the drug should report exposure by calling 800-745-4447, extension 15500.

Lactation

Not known if present in human milk. The effects on milk production and on breastfed infant not known. Available data suggest alglucosidase alfa (another hydrolytic lysosomal glycogen-specific enzyme replacement therapy) present in human milk.

Consider benefits of breastfeeding along with potential for adverse effects from infant exposure and the mother’s clinical need for the drug.

Lactating women exposed to the drug should report exposure by calling 800-745-4447, extension 15500.

Pediatric Use

Safety and efficacy established in late-onset Pompe disease (LOPD) in pediatric patients ≥1 year of age. Not approved for the treatment of infantile-onset Pompe disease (IOPD).

Safety profile in pediatric patients 1–12 years old with Pompe disease similar to that of adults and older pediatric patients.

Safety and efficacy not established in patients <1 year of age.

Geriatric Use

Studies included 14 patients 65–74 years of age and 3 patients ≥75 years of age. Recommended dosage same as in younger adult patients.

Hepatic Impairment

Effect of hepatic impairment on pharmacokinetics not evaluated.

Renal Impairment

Effect of renal impairment on pharmacokinetics not evaluated.

Common Adverse Effects

Most common adverse reactions (>5%): headache, fatigue, diarrhea, nausea, arthralgia, dizziness, myalgia, pruritus, vomiting, dyspnea, erythema, paresthesia, urticaria.

Drug Interactions

Formal drug interaction studies not conducted.

Avalglucosidase Alfa-ngpt Pharmacokinetics

Absorption

Exposure approximately dose proportional over dose range of 5–20 mg/kg (0.25–1 and 0.125–0.5 times the recommended dosage in patients weighing ≥30 kg and <30 kg, respectively).

No accumulation following every-2-week dosing interval.

Patients weighing <30 kg receiving 40 mg/kg every 2 weeks expected to have similar total exposure based on AUC as patients weighing ≥30 kg receiving 20 mg/kg every 2 weeks.

Distribution

Extent

Unknown if distributes into human milk.

Elimination

Metabolism

Protein component expected to be metabolized into small peptides and amino acids via catabolic pathways.

Half-life

Mean 1.6 hours.

Special Populations

Pharmacokinetics not altered based on age (1–78 years) or sex.

Stability

Storage

Parenteral

Lyophilized Powder

Store between 2-8ºC.

Reconstituted and Dilution Solution

Dilute reconstituted solution immediately after reconstitution; if not used immediately, store at 2–8°C for up to 24 hours; do not freeze.

If diluted solution not used immediately, store at 2–8°C for up to 24 hours. Do not freeze. Complete infusion within 9 hours after removal from the refrigerator; after 9 hours, discard diluted solution. Discard solution if refrigerated for over 24 hours. Once diluted solution is removed from the refrigerator, it may not be returned.

Actions

Pompe disease is a hereditary glycogen metabolic disorder caused by a deficiency of the lysosomal acid α-glucosidase (GAA) enzyme, which results in intralysosomal accumulation of glycogen in various tissues.
Avalglucosidase alfa provides an exogenous source of GAA. The mannose-6-phosphate (M6P) on avalglucosidase alfa mediates binding to M6P receptors on the cell surface with high affinity. After binding, the drug is internalized and transported into lysosomes where proteolysis causes increased GAA enzymatic activity. Avalglucosidase alfa then exerts enzymatic activity to cleave glycogen.

Advice to Patients

Advise patients and caregivers that infusion reactions may occur during and after avalglucosidase alfa-ngpt treatment and may include anaphylactic reactions, other serious or severe hypersensitivity reactions, and infusion-associated reactions (IARs). Inform patients of the signs and symptoms of hypersensitivity reactions and IARs and have them seek medical care should signs and symptoms occur.
Advise patients and caregivers that patients with underlying respiratory illness or compromised cardiac or respiratory function may be at risk of acute cardiorespiratory failure from volume overload during avalglucosidase alfa-ngpt infusion.
Inform pregnant or lactating women that exposure to avalglucosidase alfa-ngpt should be reported by calling 800-745-4447, extension 15500.
Inform patients and their caregivers that the Pompe Registry has been established in order to better understand the variability and progression of Pompe disease, and to continue to monitor and evaluate long-term effects of avalglucosidase alfa-ngpt. Encourage patients and their caregivers to participate in the Pompe Registry and advise them that participation is voluntary and may involve long-term follow-up. For more information regarding the registry program, visit [Web] or call 800-745-4447, extension 15500.
Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.