Nexviazyme
Generic: AVALGLUCOSIDASE ALFA-NGPT
Basic Information
Manufacturer
Genzyme Corporation
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
80eb3c9c-01d3-44fe-90ef-81df101b954d
Indications & Usage
1 INDICATIONS AND USAGE NEXVIAZYME is 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 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).
( 1 )
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).
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.1) ] Infusion-Associated Reactions (IARs) [see Warnings and Precautions (5.2) ] The most common adverse reactions (>5%) were headache, fatigue, diarrhea, nausea, arthralgia, dizziness, myalgia, pruritus, vomiting, dyspnea, erythema, paresthesia and urticaria.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genzyme at 1-800-633-1610, option 1 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse Reactions from Clinical Trials in the Pompe Disease Population The pooled safety analysis from 4 clinical trials in the Pompe disease population (including Study 1) with a mean exposure of 26 months and up to 85 months of treatment included a total of 141 NEXVIAZYME-treated patients (118 adult and 23 pediatric patients [see Clinical Studies (14.1) ] .
Adverse reactions were similar across both adult and pediatric populations.
Serious adverse reactions reported in 2 or more NEXVIAZYME-treated patients were respiratory distress, chills, and pyrexia.
A total of 4 NEXVIAZYME-treated patients in clinical trials permanently discontinued NEXVIAZYME due to adverse reactions, including 3 patients who discontinued the treatment because of a serious adverse reaction.
The most frequently reported adverse reactions (>5%) in the pooled safety population were abdominal pain, arthralgia, chills, diarrhea, dizziness, dyspnea, erythema, fatigue, flushing, headache, hypertension, hypotension, myalgia, nausea, pruritus, pyrexia, rash, vomiting, and urticaria.
Hypersensitivity reactions were reported in 67 (48%) NEXVIAZYME-treated patients, including 6 (4%) patients who reported severe hypersensitivity reactions.
Symptoms of severe hypersensitivity reactions (e.g., anaphylaxis) included chest discomfort, erythema, generalized edema, hypotension, hypoxia, rash, respiratory distress, tongue edema, and urticaria.
IARs were reported in 48 (34%) NEXVIAZYME-treated patients.
Six (4%) NEXVIAZYME-treated patients reported 13 severe IARs including symptoms of chest discomfort, decreased or increased blood pressure, dysphagia, erythema, generalized edema, hypoxia, nausea, respiratory distress, tongue edema, and urticaria.
IARs reported in more than 1 patient included chest discomfort, cyanosis, decreased or increased blood pressure, diarrhea, dizziness, erythema, fatigue, feeling hot or cold, generalized edema, headache, hyperhidrosis, hypoxia, influenza-like illness, nausea, pain, pruritus, pyrexia, rash, respiratory distress, tachycardia, throat irritation, tongue edema, tremor, urticaria, and vomiting.
Adverse Reactions from Clinical Trials in Late-Onset Pompe Disease (LOPD) In Study 1, 100 patients aged 16 to 78 years of age with LOPD (naïve to enzyme replacement therapy) were treated with either 20 mg/kg of NEXVIAZYME (n=51) or 20 mg/kg of alglucosidase alfa (n=49) given every other week as an intravenous infusion for 49 weeks followed by an open-label extension period [see Clinical Studies (14.1) ] .
During the double-blind active-controlled period of 49 weeks, serious adverse reactions were reported in 1 (2%) patient treated with NEXVIAZYME and in 3 (6%) patients treated with alglucosidase alfa.
The most frequently reported adverse reactions in (>5%) NEXVIAZYME-treated patients were headache, fatigue, diarrhea, nausea, arthralgia, dizziness, myalgia, pruritus, vomiting, dyspnea, erythema, paresthesia, and urticaria.
IARs were reported in 13 (25%) of the NEXVIAZYME-treated patients.
IARs reported in more than 1 patient on NEXVIAZYME were mild to moderate and included headache, diarrhea, pruritus, urticaria, and rash.
None of them were severe IARs.
IARs were reported in 16 (33%) patients treated with alglucosidase alfa.
IARs reported in more than 1 patient on alglucosidase alfa were mild to severe and included dizziness, flushing, dyspnea, nausea, pruritis, rash, erythema, chills, and feeling hot.
Severe IARs were reported in 2 patients treated with alglucosidase alfa.
Table 4 summarizes the adverse reactions that occurred in at least 3 NEXVIAZYME-treated patients (≥6%) in Study 1.
Study 1 was not designed to demonstrate a statistically significant difference in the incidence of adverse reactions in the NEXVIAZYME and the alglucosidase alfa treatment groups.
Table 4: Adverse Reactions Reported in at Least 6% of NEXVIAZYME-Treated Patients with LOPD in Study 1 Adverse Reaction NEXVIAZYME (N=51) n (%) Alglucosidase Alfa (N=49) n (%) Headache 11 (22%) 16 (33%) Fatigue 9 (18%) 7 (14%) Diarrhea 6 (12%) 8 (16%) Nausea 6 (12%) 7 (14%) Arthralgia 5 (10%) 8 (16%) Dizziness 5 (10%) 4 (8%) Myalgia 5 (10%) 7 (14%) Pruritus 4 (8%) 4 (8%) Vomiting 4 (8%) 3 (6%) Dyspnea 3 (6%) 4 (8%) Erythema 3 (6%) 3 (6%) Paresthesia 3 (6%) 2 (4%) Urticaria 3 (6%) 1 (2%) Immunogenicity: Anti-Drug Antibody-Associated Adverse Reactions In enzyme replacement therapy (ERT)-naïve NEXVIAZYME-treated patients (mean of 47 months, up to 100 months of treatment), the incidence of [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.6) ] IARs was 69% (9/13) in patients with an anti-drug antibody (ADA) peak titer ≥12,800, compared with incidences of 27% (12/44) in those with ADA peak titer <12,800 and 33% (1/3) in those who were ADA-negative .
In ERT-experienced adult patients, the incidence of IARs and hypersensitivity reactions were higher in patients who developed ADA compared to patients who were ADA-negative [see Clinical Pharmacology (12.6) ].
In adults, one ERT-naïve patient (ADA peak titer 3,200) and 2 ERT-experienced patients (peak ADA titers; 800 and 12,800, respectively) developed anaphylaxis.
One ERT-experienced pediatric patient (peak ADA titer 6,400) developed anaphylaxis [see Warnings and Precautions (5.1) ].
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genzyme at 1-800-633-1610, option 1 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse Reactions from Clinical Trials in the Pompe Disease Population The pooled safety analysis from 4 clinical trials in the Pompe disease population (including Study 1) with a mean exposure of 26 months and up to 85 months of treatment included a total of 141 NEXVIAZYME-treated patients (118 adult and 23 pediatric patients [see Clinical Studies (14.1) ] .
Adverse reactions were similar across both adult and pediatric populations.
Serious adverse reactions reported in 2 or more NEXVIAZYME-treated patients were respiratory distress, chills, and pyrexia.
A total of 4 NEXVIAZYME-treated patients in clinical trials permanently discontinued NEXVIAZYME due to adverse reactions, including 3 patients who discontinued the treatment because of a serious adverse reaction.
The most frequently reported adverse reactions (>5%) in the pooled safety population were abdominal pain, arthralgia, chills, diarrhea, dizziness, dyspnea, erythema, fatigue, flushing, headache, hypertension, hypotension, myalgia, nausea, pruritus, pyrexia, rash, vomiting, and urticaria.
Hypersensitivity reactions were reported in 67 (48%) NEXVIAZYME-treated patients, including 6 (4%) patients who reported severe hypersensitivity reactions.
Symptoms of severe hypersensitivity reactions (e.g., anaphylaxis) included chest discomfort, erythema, generalized edema, hypotension, hypoxia, rash, respiratory distress, tongue edema, and urticaria.
IARs were reported in 48 (34%) NEXVIAZYME-treated patients.
Six (4%) NEXVIAZYME-treated patients reported 13 severe IARs including symptoms of chest discomfort, decreased or increased blood pressure, dysphagia, erythema, generalized edema, hypoxia, nausea, respiratory distress, tongue edema, and urticaria.
IARs reported in more than 1 patient included chest discomfort, cyanosis, decreased or increased blood pressure, diarrhea, dizziness, erythema, fatigue, feeling hot or cold, generalized edema, headache, hyperhidrosis, hypoxia, influenza-like illness, nausea, pain, pruritus, pyrexia, rash, respiratory distress, tachycardia, throat irritation, tongue edema, tremor, urticaria, and vomiting.
Adverse Reactions from Clinical Trials in Late-Onset Pompe Disease (LOPD) In Study 1, 100 patients aged 16 to 78 years of age with LOPD (naïve to enzyme replacement therapy) were treated with either 20 mg/kg of NEXVIAZYME (n=51) or 20 mg/kg of alglucosidase alfa (n=49) given every other week as an intravenous infusion for 49 weeks followed by an open-label extension period [see Clinical Studies (14.1) ] .
During the double-blind active-controlled period of 49 weeks, serious adverse reactions were reported in 1 (2%) patient treated with NEXVIAZYME and in 3 (6%) patients treated with alglucosidase alfa.
The most frequently reported adverse reactions in (>5%) NEXVIAZYME-treated patients were headache, fatigue, diarrhea, nausea, arthralgia, dizziness, myalgia, pruritus, vomiting, dyspnea, erythema, paresthesia, and urticaria.
IARs were reported in 13 (25%) of the NEXVIAZYME-treated patients.
IARs reported in more than 1 patient on NEXVIAZYME were mild to moderate and included headache, diarrhea, pruritus, urticaria, and rash.
None of them were severe IARs.
IARs were reported in 16 (33%) patients treated with alglucosidase alfa.
IARs reported in more than 1 patient on alglucosidase alfa were mild to severe and included dizziness, flushing, dyspnea, nausea, pruritis, rash, erythema, chills, and feeling hot.
Severe IARs were reported in 2 patients treated with alglucosidase alfa.
Table 4 summarizes the adverse reactions that occurred in at least 3 NEXVIAZYME-treated patients (≥6%) in Study 1.
Study 1 was not designed to demonstrate a statistically significant difference in the incidence of adverse reactions in the NEXVIAZYME and the alglucosidase alfa treatment groups.
Table 4: Adverse Reactions Reported in at Least 6% of NEXVIAZYME-Treated Patients with LOPD in Study 1 Adverse Reaction NEXVIAZYME (N=51) n (%) Alglucosidase Alfa (N=49) n (%) Headache 11 (22%) 16 (33%) Fatigue 9 (18%) 7 (14%) Diarrhea 6 (12%) 8 (16%) Nausea 6 (12%) 7 (14%) Arthralgia 5 (10%) 8 (16%) Dizziness 5 (10%) 4 (8%) Myalgia 5 (10%) 7 (14%) Pruritus 4 (8%) 4 (8%) Vomiting 4 (8%) 3 (6%) Dyspnea 3 (6%) 4 (8%) Erythema 3 (6%) 3 (6%) Paresthesia 3 (6%) 2 (4%) Urticaria 3 (6%) 1 (2%) Immunogenicity: Anti-Drug Antibody-Associated Adverse Reactions In enzyme replacement therapy (ERT)-naïve NEXVIAZYME-treated patients (mean of 47 months, up to 100 months of treatment), the incidence of [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.6) ] IARs was 69% (9/13) in patients with an anti-drug antibody (ADA) peak titer ≥12,800, compared with incidences of 27% (12/44) in those with ADA peak titer <12,800 and 33% (1/3) in those who were ADA-negative .
In ERT-experienced adult patients, the incidence of IARs and hypersensitivity reactions were higher in patients who developed ADA compared to patients who were ADA-negative [see Clinical Pharmacology (12.6) ].
In adults, one ERT-naïve patient (ADA peak titer 3,200) and 2 ERT-experienced patients (peak ADA titers; 800 and 12,800, respectively) developed anaphylaxis.
One ERT-experienced pediatric patient (peak ADA titer 6,400) developed anaphylaxis [see Warnings and Precautions (5.1) ].