BRIEF SUMMARY

AVAGLUCOSIDASE-alfa-ngpt- (Aug 2021)

Indn-   To treat late-onset Pompe disease  

Comp-  ­ For injection: 100 mg of avalglucosidase alfa-ngpt as a lyophilized powder in a single-dose vial for reconsti

is administered as intravenous infusion. For patients weighing :   o =30 kg, the recommended dosage is 20 mg/kg (of actual body weight) every two weeks. o <30 kg, the recommended dosage is 40 mg/kg (of actual body weight) every two weeks .

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

CI-   None.

WARNINGS -

Hypersensitivity Reactions Including Anaphylaxis •Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available. If a severe hypersensitivity reaction occurs,  should be discontinued immediately and appropriate medical treatment should be initiated.

Pat Inform-

Hypersensitivity Reactions (Including Anaphylaxis) and Infusion-Associated Reactions (IARs) -                                                                                                     Advise the patients and caregivers that reactions related to the infusion may occur during and after  treatment, including anaphylactic reactions, other serious or severe hypersensitivity reactions, and IARs.

Inform patients of the signs and symptoms of hypersensitivity reactions and IARs and have them seek medical care should signs and symptoms occur

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U.S. FDA GLUAPPROVED DRUGS SURING 2021                                          

Serial No 34

Name of the Drug-    NEXVIAZYME

Active Ingredient -   Avaglucosidase alfa -ngpt

Pharmacological Classification- To treat late-onset Pompe disease                                                                                                                                                                                                                                                

 Date of Approval-          8/6/2021

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use                         NEXVIAZYME™ safely and effectively.

ee full prescribing information for NEXVIAZYME. NEXVIAZYME (avalglucosidase alfa-ngpt) for injection, for intravenous use

Initial U.S. Approval: 2021

WARNING:                                                                                                                      SEVERE HYPERSENSITIVITY REACTIONS, INFUSION-ASSOCIATED REACTIONS, and RISK OF ACUTE CARDIORESPIRATORY FAILURE IN SUSCEPTIBLE PATIENTS See full prescribing information for complete boxed 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.

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). 

ADVERSE REACTIONS-

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

CONTRAINDICATIONS-

­ None.

WARNINGS AND PRECAUTIONS-

­ See boxed warning. (under Indications)

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). 

DOSAGE AND ADMINISTRATION-

­ • Consider administering antihistamines, antipyretics, and/or corticosteroids prior to NEXVIAZYME administration to reduce the risk of IARs.

 • Must be reconstituted and diluted prior to use.

• See full prescribing information for administration instructions including the recommended infusion rate schedule.

 • NEXVIAZYME is administered as intravenous infusion. For patients weighing :             o =30 kg, the recommended dosage is 20 mg/kg (of actual body weight) every two weeks. o <30 kg, the recommended dosage is 40 mg/kg (of actual body weight) every two weeks .

• See the full prescribing information for dosage modifications due to hypersensitivity reactions or IARs.

DOSAGE FORMS AND STRENGTHS- 

­ For injection: 100 mg of avalglucosidase alfa-ngpt as a lyophilized powder in a single-dose vial for reconstitution.

PATIENT COUNSELING INFORMATION-

Hypersensitivity Reactions (Including Anaphylaxis) and Infusion-Associated Reactions (IARs) -                                                                                                     Advise the patients and caregivers that reactions related to the infusion may occur during and after NEXVIAZYME treatment, including anaphylactic reactions, other serious or severe hypersensitivity reactions, and IARs.

Inform patients of the signs and symptoms of hypersensitivity reactions and IARs and have them seek medical care should signs and symptoms occur

Risk of Acute Cardiorespiratory Failure-                                                                        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 NEXVIAZYME infusion

NEXVIAZYME Exposure During Pregnancy or Lactation-                                     Pregnant or lactating women exposed to NEXVIAZYME, or their healthcare providers, should report NEXVIAZYME exposure by calling 1-800-745-4447, extension 15500. Reference ID: 4837490 16 Pompe Registry

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 NEXVIAZYME.

Patients and their caregivers should be encouraged to participate in the Pompe Registry and advised that their participation is voluntary and may involve long-term follow-up.

Manufactured by: Genzyme Corporation Cambridge, MA 02142 U.S. License Number: 1596

CLINICAL PHARMACOLOGY

1. 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 a-glucosidase (GAA), which results in intralysosomal accumulation of glycogen in various tissues.

2. Pharmacodynamics-                                                                                                    In patients with Pompe disease, excess of glycogen is degraded to hexose tetrasaccharide (Hex4) which is then excreted in urine. The urinary Hex4 assay measures its major component, glucose tetrasaccharide (Glc4).

3. Pharmacokinetics-                                                                                                    The avalglucosidase alfa-ngpt exposure increases in an approximately proportional manner with increasing doses over a range from 5 to 20 mg/kg (0.25 to 1 time the approved recommended dosage in LOPD patients weighing =30 kg or 0.125 to 0.5 times the approved recommended dosage in LOPD patients weighing <30 kg).

Distribution-                                                                                                                   The volume of distribution of avalglucosidase alfa-ngpt was 3.4 L in LOPD patients.

Elimination-                                                                                                                    The mean avalglucosidase alfa-ngpt plasma elimination half-life was 1.6 hours in LOPD patients. The mean avalglucosidase alfa-ngpt clearance was 0.9 L/hour.

Metabolism-                                                                                                                   The metabolic pathway of avalglucosidase alfa-ngpt has not been characterized. The protein portion of avalglucosidase alfa-ngpt is expected to be metabolized into small peptides and amino acids via catabolic pathways.

Specific Populations-                                                                                             Population pharmacokinetic analyses indicated that age and sex did not significantly influence the pharmacokinetics of avalglucosidase alfa-ngpt in patients with Pompe disease aged 1 to 78 years.

Pediatric patients In 16 patients aged 1 to 12 years with Pompe disease, following a 4-hour intravenous infusion of NEXVIAZYME 20 mg/kg every two weeks and 7-hour intravenous infusion of NEXVIAZYME 40 mg/kg every two weeks, the mean Cmax ranged from 175 to 189 µg/mL and 250 to 403 µg/mL, respectively.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-

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. 

The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

2. Lactation Risk Summary -                                                                                        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.

3. 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

 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 Reference ID: 4837490 11 patients younger than 1 year of age.

4. 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