Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication 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 ) FDA label
Also known as avalglucosidase alfa, Nexviazyme, neoGAA
GZ402666 · 5 trials · 7 indications
FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Least square (LS) mean and standard error (SE) were derived from mixed model for repeated measure (MMRM) model with baseline FVC \[percent (%) predicted, as continuous\], sex, age (in years at baseline), treatment group, visit, interaction term between treatment group and visit as fixed effects. Percent of predicted FVC = (actual FVC measurement)/(predicted value of FVC) \* 100. After non-inferiority (NI) testing, a test for superiority of avalglucosidase alfa versus alglucosidase alfa was performed with an overall 2-sided 5% level of significance.
Adverse event (AE): any untoward medical occurrence in participant received study drug \& did not necessarily had to have causal relationship with treatment. TEAEs: AEs developed/worsened in grade/become serious during PAP period (from the time of 1st study drug dose up to Week 25). Serious AE(SAE): any untoward medical occurrence at any dose resulted in death, was life-threatening, required inpatient hospitalization, prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically important event. TEAEs included SAEs \& non-SAEs. AESI:AE (serious/non-serious) of scientific \& medical concern specific to Sponsor's product/program, for which ongoing monitoring \& immediate notification by Investigator to Sponsor required.
IARs were defined as AESIs that occurred during either the infusion or the observation period following the infusion which were deemed to be related or possibly related to the study drug. Protocol-defined IARs: An AESIs that occurred during either the infusion or the observation period following the infusion which were deemed to be related or possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 or 2 criteria: 1) event occurred from the start of infusion to the end of infusion plus 24 hours, and considered related to study drug, 2) If an AE time component was missing, compared AE Start date with infusion start date and infusion end date. If an AE Start date was between infusion start date and infusion end date plus one day, and it was related to study drug.
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An serious AE (SAE) is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. TEAEs are defined as AEs that develop or worsen during the on-treatment period (that is, from the time of first dose of IMP up to 4 weeks after the last administration of the IMP). Protocol-defined IARs were defined as AEs that occur during either the infusion or the post-infusion observation period (that is, up to 2 hours or longer following the infusion as per the Investigator's discretion) which were deemed to be related or possibly related to the IMP.
Physical examination included, at a minimum, an assessment of the participant's general appearance; skin; head, eyes, ears, nose, and throat; examinations of lymph nodes, abdomen, extremities/joints, neurological and mental status; heart and respiratory auscultation; peripheral arterial pulse; and pupil, knee, achilles, and plantar reflexes.
Blood samples were collected to determine the clinical chemistry laboratory abnormalities.
Blood samples were collected to determine the hematology laboratory significant abnormalities.
Last on-treatment (LOT) values were collected at or just prior to the last IMP administration.
The LOT values were collected at or just prior to the last IMP administration.
The LOT values were collected at or just prior to the last IMP administration.
The LOT values were collected at or just prior to the last IMP administration.
The LOT values were collected at or just prior to the last IMP administration.
Participants vital signs were examined to determine the abnormalities. Vital signs included heart rate, systolic and diastolic blood pressure.
Body weight was measured in kilograms and collected in the electronic case report forms every 3 months throughout the duration of the study, as well as at the end of study visit.
Standard 12-lead ECGs were recorded after at least 15 minutes in the supine position using an electrocardiographic device. The following were assessed: heart rate, rhythm, interval between the peaks of successive QRS complexes (RR), interval from the beginning of the P wave until the beginning of the QRS complex (PR), interval from start of the Q wave to the end of the S wave (QRS), interval between the start of the Q wave and the end of the T wave (QT), QT interval corrected for heart rate (QTc) automatic correction evaluation (by the ECG device), QRS axis, R voltage V6, voltage V1, left ventricular hypertrophy criteria, right ventricular hypertrophy criteria, repolarization charges, and overall cardiac impression for each participant.
ADA negative was defined as ADAs are not detected (that is, negative in screening assay or reactive in screening but negative in confirmatory assay). ADA positive was defined as ADA was detected (that is, an assay signal equal to or greater than the cut-point in the screening assay and was tested positive in the confirmatory assay).
Cmax was defined as maximum plasma concentration observed. The non-compartmental pharmacokinetic (PK) analysis was performed.
AUClast was calculated using the trapezoidal method from time zero to the real time. The non-compartmental PK analysis was performed.
Tlast was defined as time corresponding to the last concentration above the limit of quantification, Clast. The non-compartmental PK analysis was performed.
t1/2z was calculated according to the following equation: t1/2z = 0.693/λz. Where, λz is the slope of the regression line of the terminal phase of the plasma concentration versus time curve. Half-life was calculated by taking the regression of at least 3 points. The non-compartmental PK analysis was performed.
CLss was calculated using the following equation: CLss= dose/AUC. The non-compartmental PK analysis was performed.
Vss was calculated using the following equation: Vz= CLss/λz. The non-compartmental PK analysis was performed.
| Arm | Type | Description |
|---|---|---|
| Avalglucosidase alfa | EXPERIMENTAL | Administered intravenously every 2 weeks |
| avalglucosidase alfa (GZ402666) | EXPERIMENTAL | Administered intravenously every 2 weeks |
| alglucosidase alfa (GZ419829) | ACTIVE_COMPARATOR | Administered intravenously every 2 weeks |
| Cohort 1: Avalglucosidase Alfa 20 mg/kg | EXPERIMENTAL | Avalglucosidase alfa, 20 mg/kg intravenous (IV) infusion every other week (qow) for 25 weeks in the Primary Analysis Period (PAP), followed by same treatment from Week 26 up to Week 371 in extension treatment period (ETP). |
| Cohort 2: Avalglucosidase Alfa 40 mg/kg | EXPERIMENTAL | Avalglucosidase alfa 40 mg/kg IV infusion qow for 25 weeks in the PAP, followed by same treatment from Week 26 up to Week 371 in ETP. |
| Cohort 3a: Avalglucosidase Alfa 40 mg//kg | EXPERIMENTAL | After determination of the highest tolerated avalglucosidase alfa dose in Cohort 1 and Cohort 2 (after at least 5 participants in each Cohort 1 and Cohort 2 had received the 7th dose of avalglucosidase alfa or completed Week 13 with a minimum of 6 infusions), participants received avalglucosidase alfa 40 mg/kg (the highest tolerated dose) IV infusion qow for 25 weeks in PAP, followed by same treatment from Week 26 up to Week 371 in ETP. |
| Cohort 3b: Alglucosidase Alfa in PAP | EXPERIMENTAL | After determination of the highest tolerated avalglucosidase alfa dose in Cohort 1 and Cohort 2 (after at least 5 participants in each Cohort 1 and Cohort 2 had received the 7th dose of avalglucosidase alfa or completed Week 13 with a minimum of 6 infusions), participants received alglucosidase alfa at their current stable dose (defined as dose \[between 20 mg/kg qow and 40 mg/kg weekly as per physician\] administered regularly for a minimum of 6 months immediately prior to entry in this study) IV infusion for 25 weeks in PAP. After PAP, participants received avalglucosidase alfa 40mg/kg IV infusion qow from Week 26 up to Week 371 in ETP. |
| GZ402666 (neoGAA) Group 1 - 5 mg | EXPERIMENTAL | Intravenous infusion of 5mg neoGAA to treatment naïve late onset Pompe disease patients once every other week for a total of 24 weeks |
| GZ402666 (neoGAA) Group 1 - 10 mg | EXPERIMENTAL | Intravenous infusion of 10mg neoGAA to treatment naïve late onset Pompe disease patients once every other week for a total of 24 weeks. |
| GZ402666 (neoGAA) Group 1 - 20 mg | EXPERIMENTAL | Intravenous infusion of 20mg neoGAA to treatment naïve late onset Pompe disease patients once every other week for a total of 24 weeks. |
| GZ402666 (neoGAA) Group 2 - 5 mg | EXPERIMENTAL | Intravenous infusion of 5mg neoGAA once every other week for a total of 24 weeks to late onset Pompe disease patients previously treated with alglucoside alfa. |
| GZ402666 (neoGAA) Group 2 - 10 mg | EXPERIMENTAL | Intravenous infusion of 10mg neoGAA once every other week for a total of 24 weeks to late onset Pompe disease patients previously treated with alglucoside alfa. |
| GZ402666 (neoGAA) Group 2 - 20 mg | EXPERIMENTAL | Intravenous infusion of 20mg neoGAA once every other week for a total of 24 weeks to late onset Pompe disease patients previously treated with alglucoside alfa. |
| Name | Type | Description |
|---|---|---|
| avalglucosidase alfa | DRUG | Sterile lyophilized powder intravenous (IV) infusion |
| Avalglucosidase alfa (GZ402666) | DRUG | Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous |
| Alglucosidase alfa (GZ419829) | DRUG | Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous |
| GZ402666 | DRUG | Pharmaceutical form:lyophilized powder reconstituted for infusion Route of administration: intravenous |
Inclusion Criteria: * Participants must have confirmed diagnosis of infantile-onset Pompe disease defined as: the presence of 2 lysosomal acid α-glucosidase (GAA) pathogenic variants and a documented GAA deficiency from blood, skin, or muscle tissue; or the presence of 1 GAA pathogenic variant and ...
GZ402666 is an investigational small molecule being developed by Sanofi for the treatment of Pompe Disease, also known as Glycogen Storage Disease Type II (GSD II) or Acid Maltase Deficiency. It is currently in Phase 1 clinical development and has not been approved by regulatory authorities.
GZ402666 is being developed by Sanofi, a multinational pharmaceutical company traded on the stock exchange under the ticker symbol SNY. The drug is an investigational small molecule intended for the treatment of Pompe Disease, a rare genetic disorder.
GZ402666 is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA or any other regulatory agency. The drug is being studied for the treatment of Pompe Disease, also known as Glycogen Storage Disease Type II.
GZ402666 has been studied in one completed Phase 1 clinical trial with the identifier NCT01898364. This trial evaluated the safety and efficacy of repeat dosing in late onset Pompe Disease patients and enrolled 24 participants across multiple countries including the United States, Belgium, Denmark, France, Germany, Netherlands, and the United Kingdom.
GZ402666 is associated with the trial NCT01898364, which evaluates repeat neoGAA dosing in late onset Pompe Disease patients. The trial title refers to neoGAA, suggesting that GZ402666 may be the same compound as neoGAA, though this is not explicitly confirmed in the available data.