COMET TRIAL
At 49 weeks, the safety profile of NEXVIAZYME was well established1
No patients in the NEXVIAZYME group reported a severe IAR and 1 (2%) patient reported a serious AR over 49 weeks in the COMET trial.
Adverse reactions reported in ≥6% of patients treated with NEXVIAZYME1
| ADVERSE REACTION |
NEXVIAZYME |
ALGLUCOSIDASE ALFA |
| 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%) |
NEXVIAZYME IARs and ARs in the COMET trial
IARs
25% (13/51) of patients receiving NEXVIAZYME
33% (16/49) of patients receiving alglucosidase alfa
Mild-to-moderate IARs reported in >1 patient receiving NEXVIAZYME were headache, diarrhea, pruritus, urticaria, and rash
SEVERE IARs
0 patients receiving NEXVIAZYME
4% (2/49) of patients receiving alglucosidase alfa
SERIOUS ARs
2% (1/51) of patients receiving NEXVIAZYME
6% (3/49) of patients receiving alglucosidase alfa
The COMET trial was not designed to demonstrate a statistically significant difference in the incidence of ARs between NEXVIAZYME and alglucosidase alfa.
AR=adverse reaction; IAR=infusion-associated reaction.
NEXVIAZYME’s overall safety profile was observed in patients up to 145 weeks, including in those who switched from alglucosidase alfa2
No new safety concerns were observed during the ETP.
| ADVERSE EVENTS |
NEXVIAZYME arm |
Switch arm |
| All TEAEs | 50 (98%) | 43 (98%) |
| TEAEs potentially related to treatment | 27 (53%) | 25 (57%) |
| Serious TEAEs | 18 (35%) | 12 (27%) |
| Serious TEAEs potentially related to treatment | 4 (8%) | 2 (5%) |
| Severe TEAEs | 12 (24%) | 10 (23%) |
| TEAEs leading to permanent treatment discontinuation† | 2 (4%) | 3 (7%) |
| TEAEs leading to death | 0 | 1 (2%)‡ |
| Protocol-defined IARs§ | 21 (41%) | 21 (48%) |
Numbers reported are the number (%) of participants with at least 1 TEAE in each category. The mean (SD) duration of exposure during the ETP at the data cut-off date (March 11, 2022) was 141.19 (45.31) weeks (range, 20.00-223.50 weeks) for the NEXVIAZYME arm and 138.27 (53.55) weeks (range, 7.83-230.02 weeks) for the switch arm.
*Data for the switch arm are for the ETP only while participants were receiving avalglucosidase alfa; this group had received alglucosidase alfa during the PAP.
†5 participants discontinued treatment during the ETP by week 145 for 6 adverse events (treatment-related: ocular hyperemia and erythema [experienced by the same participant], urticaria, respiratory distress; non-treatment related: acute myocardial infarction, pancreatic adenocarcinoma).
‡Pancreatic adenocarcinoma considered not related to treatment.
§Defined as an adverse event that occurred during either the infusion or observation period following the infusion, related or possibly related to the investigational treatment.
TEAEs=treatment-emergent adverse events.
Switch and long-term efficacy data is available2
Walking and breathing ability was observed up to 145 weeks in patients receiving NEXVIAZYME, including those who switched from alglucosidase alfa at 49 weeks.
Pooled safety data1
A long-term look at the NEX move
Up to 7 years1,3
- Pooled safety analysis was gathered for 141 patients with Pompe disease treated with NEXVIAZYME (118 adult and 23 pediatric), including patients who switched from alglucosidase alfa
Treatment discontinuation1
- 4% (5/141) of NEXVIAZYME-treated patients permanently discontinued treatment due to adverse reactions
- 2 of the 5 patients discontinued because of serious adverse reactions
Infusion-associated reactions1
- 34% (48/141) of NEXVIAZYME-treated patients reported IARs. IARs reported in >1 patient included chills, cough, diarrhea, erythema, fatigue, headache, influenza-like illness, nausea, ocular hyperemia, pain in extremity, pruritus, rash, rash erythematous, tachycardia, urticaria, vomiting, chest discomfort, dizziness, hyperhidrosis, lip swelling, oxygen saturation decreased, pain, palmar erythema, swollen tongue, abdominal pain upper, burning sensation, eyelid edema, feeling cold, flushing, respiratory distress, throat irritation, and tremor
Serious adverse reactions1
- In 2 or more NEXVIAZYME-treated patients, respiratory distress, chills, and pyrexia were reported
- Serious AEs were similar across both adult and pediatric populations
Up to 7 years1,3
- In >5% of patients receiving NEXVIAZYME, headache, diarrhea, nausea, fatigue, arthralgia, myalgia, dizziness, rash, vomiting, pyrexia, abdominal pain, pruritus, erythema, abdominal pain upper, chills, cough, urticaria, dyspnea, hypertension, and hypotension were reported
Immunogenicity and antidrug antibodies (ADA)1
ADA activity was monitored in NEXVIAZYME-treated patients for up to 7 years.
Incidence of anti-NEXVIAZYME antibodies in patients with Pompe disease1
Most adults and some children developed ADA following treatment with NEXVIAZYME. Most ADA were not neutralizing antibodies (NAbs).
In NEXVIAZYME-treated patients (mean 26 months, up to 7 years of treatment)
Incidence of IARs
62% (8/13) in those with ADA peak titer ≥12,800
19% (8/43) in those with ADA titer <12,800
33% (1/3) in those who were ADA negative
Incidence of hypersensitivity reactions
31% (4/13) in those with higher ADA titers
14% (2/14) in those with lower ADA titers
In ERT-experienced adult patients who
switched to NEXVIAZYME
Increased incidence of IARs and hypersensitivity reactions in those patients who developed ADA versus those who were ADA negative.
One treatment-naive patient (ADA peak titer 3200) and 2 treatment-experienced patients (ADA peak titers; 800 and 12,800, respectively) developed anaphylaxis.
Seroconversion
The median time to seroconversion was 8 weeks.
|
|
NEXVIAZYME1 |
|||
|
|
Treatment-Naive |
Treatment-Experienced Patients: |
||
|
|
Adults/Pediatrics |
Adults |
Pediatrics |
Pediatrics |
|
|
n (%) |
n (%) |
n (%) |
n (%) |
|
ADA at |
2 (3%) |
43 (74%) |
1 (17%) |
1 (10%) |
|
ADA after |
58 (95%) |
32 (55%) |
1 (17%) |
5 (50%) |
|
Neutralizing Antibody (NAb) |
||||
|
Both NAb |
13 (21%) |
3 (5%) |
0 |
0 |
|
Inhibition |
17 (28%) |
10 (18%) |
0 |
0 |
|
Inhibition |
24 (39%) |
12 (21%) |
0 |
1 (10%) |
The development of ADA did not have an apparent impact on clinical efficacy or pharmacokinetics.
A trend toward decreased pharmacodynamic response was observed in patients with ADA peak titer ≥12,800.
Antibody detection is highly dependent on assay performance and can be influenced by several factors. For these reasons, comparing antibody incidence rates between studies may be misleading.
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WARNING: SEVERE HYPERSENSITIVITY REACTIONS, INFUSION-ASSOCIATED REACTIONS, and RISK OF ACUTE CARDIORESPIRATORY FAILURE IN SUSCEPTIBLE PATIENTS Hypersensitivity Reactions including Anaphylaxis Patients treated with NEXVIAZYME have experienced life-threatening hypersensitivity reactions, including anaphylaxis. 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. In patients with severe hypersensitivity reaction, a desensitization procedure to NEXVIAZYME may be considered. Infusion-Associated Reactions (IARs) Patients treated with NEXVIAZYME have experienced severe IARs. 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. Patients with an acute underlying illness at the time of NEXVIAZYME infusion may be at greater risk for IARs. Patients with advanced Pompe disease may have compromised cardiac and respiratory function, which may predispose them to a higher risk of severe complications from IARs. 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 NEXVIAZYME infusion. More frequent monitoring of vitals should be performed during NEXVIAZYME infusion. |
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions Including Anaphylaxis: See Boxed WARNING. Prior to NEXVIAZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. 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.
Infusion-Associated Reactions: See Boxed WARNING. IARs may still occur in patients after receiving pretreatment. 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: See Boxed WARNING.
ADVERSE REACTIONS
The most common adverse reactions (>5%) were headache, fatigue, diarrhea, nausea, arthralgia, dizziness, myalgia, pruritus, vomiting, dyspnea, erythema, paresthesia and urticaria.
INDICATION
NEXVIAZYME (avalglucosidase alfa-ngpt) is indicated for the treatment of patients 1 year of age and older with late-onset Pompe disease [lysosomal acid alpha-glucosidase (GAA) deficiency].
Please see full Prescribing Information for complete details, including Boxed WARNING.
References: 1. NEXVIAZYME (avalglucosidase alfa-ngpt) [prescribing information]. Genzyme Corporation, Cambridge, MA; 2023. 2. Data on file. Genzyme Corporation.
|
WARNING: SEVERE HYPERSENSITIVITY REACTIONS, INFUSION-ASSOCIATED REACTIONS, and RISK OF ACUTE CARDIORESPIRATORY FAILURE IN SUSCEPTIBLE PATIENTS Hypersensitivity Reactions including Anaphylaxis Patients treated with NEXVIAZYME have experienced life-threatening hypersensitivity reactions, including anaphylaxis. 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. In patients with severe hypersensitivity reaction, a desensitization procedure to NEXVIAZYME may be considered. Infusion-Associated Reactions (IARs) Patients treated with NEXVIAZYME have experienced severe IARs. 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. Patients with an acute underlying illness at the time of NEXVIAZYME infusion may be at greater risk for IARs. Patients with advanced Pompe disease may have compromised cardiac and respiratory function, which may predispose them to a higher risk of severe complications from IARs. 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 NEXVIAZYME infusion. More frequent monitoring of vitals should be performed during NEXVIAZYME infusion. |
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions Including Anaphylaxis: See Boxed WARNING. Prior to NEXVIAZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. 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.
Infusion-Associated Reactions: See Boxed WARNING. IARs may still occur in patients after receiving pretreatment. 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: See Boxed WARNING.
ADVERSE REACTIONS
The most common adverse reactions (>5%) were headache, fatigue, diarrhea, nausea, arthralgia, dizziness, myalgia, pruritus, vomiting, dyspnea, erythema, paresthesia and urticaria.
INDICATION
NEXVIAZYME (avalglucosidase alfa-ngpt) is indicated for the treatment of patients 1 year of age and older with late-onset Pompe disease [lysosomal acid alpha-glucosidase (GAA) deficiency].
Please see full Prescribing Information for complete details, including Boxed WARNING.
References: 1. NEXVIAZYME (avalglucosidase alfa-ngpt) [prescribing information]. Genzyme Corporation, Cambridge, MA; 2023. 2. Data on file. Genzyme Corporation.