Zolgensma

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zolgensma 2 × 1013 vector genomes/mL solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
2.1 General description 
 
Onasemnogene abeparvovec is a gene therapy medicinal product that expresses the human survival 
motor neuron (SMN) protein. It is a non replicating recombinant adeno associated virus serotype 9 
(AAV9) based vector containing the cDNA of the human SMN gene under the control of the 
cytomegalovirus enhancer/chicken-β-actin-hybrid promoter. 
 
Onasemnogene abeparvovec is produced in human embryonic kidney cells by recombinant DNA 
technology. 
 
2.2 Qualitative and quantitative composition 
 
Each mL contains onasemnogene abeparvovec with a nominal concentration of 2 × 1013 vector 
genomes (vg). Vials will contain an extractable volume of not less than either 5.5 mL or 8.3 mL. The 
total number of vials and combination of fill volumes in each finished pack will be customised to meet 
dosing requirements for individual patients depending on their weight (see sections 4.2 and 6.5). 
 
Excipient with known effect 
This medicinal product contains 0.2 mmol sodium per mL (see section 4.4). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for infusion. 
When thawed, it is a clear to slightly opaque, colourless to faint white solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Zolgensma is indicated for the treatment of: 
-  patients with 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the SMN1 gene 

and a clinical diagnosis of SMA Type 1, or  
-   patients with 5q SMA with a bi-allelic mutation in the SMN1 gene and up to 3 copies of the 

SMN2 gene. 
 
4.2 Posology and method of administration 
 
Treatment should be initiated and administered in clinical centres and supervised by a physician 
experienced in the management of patients with SMA.  
 



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Before administration of onasemnogene abeparvovec, baseline laboratory testing is required, 
including: 
• AAV9 antibody testing using an appropriately validated assay 
• liver function: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total 

bilirubin, 
• platelet count, and 
• troponin-I. 
 
The need for close monitoring of liver function, platelet count and troponin-I after administration and 
the need for corticosteroid treatment are to be considered when establishing the timing of 
onasemnogene abeparvovec treatment (see section 4.4). 
 
In case of acute or chronic uncontrolled active infections, treatment should be postponed until the 
infection has resolved or is controlled (see sub-sections 4.2 and 4.4 immunomodulatory regimen).  
 
Posology 
 
For single-dose intravenous infusion only.  
 
Patients will receive a dose of nominal 1.1 x 1014 vg/kg onasemnogene abeparvovec. The total volume 
is determined by patient body weight.  
 
Table 1 gives the recommended dosing for patients who weigh 2.6 to 21.0 kg.  
 
Table 1 Recommended dosing based on patient body weight 

Patient weight range (kg) Dose (vg) Total volume of dose a (mL) 
2.6 – 3.0 3.3 × 1014 16.5 
3.1 – 3.5 3.9 × 1014 19.3 
3.6 – 4.0 4.4 × 1014 22.0 
4.1 – 4.5 5.0 × 1014 24.8 
4.6 – 5.0 5.5 × 1014 27.5 
5.1 – 5.5 6.1 × 1014 30.3 
5.6 – 6.0 6.6 × 1014 33.0 
6.1 – 6.5 7.2 × 1014 35.8 
6.6 – 7.0 7.7 × 1014 38.5 
7.1 – 7.5 8.3 × 1014 41.3 
7.6 – 8.0 8.8 × 1014 44.0 
8.1 – 8.5 9.4 × 1014 46.8 
8.6 – 9.0 9 .9 x 1014 49.5 
9.1 – 9.5 1.05 x 1015 52.3 
9.6 – 10.0 1.1 x 1015 55.0 

10.1 – 10.5 1.2 x 1015 57.8 
10.6 – 11.0 1.21 x 1015 60.5 
11.1 – 11.5 1.27 x 1015 63.3 
11.6 – 12.0 1.32 x 1015 66.0 
12.1 – 12.5 1.36 x 1015 68.8 
12.6 – 13.0 1.44 x 1015 71.5 
13.1 – 13.5 1.49 x 1015 74.3 



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Patient weight range (kg) Dose (vg) Total volume of dose a (mL) 
13.6 – 14.0 1.54  x  1015 77.0 
14.1 – 14.5 1.59  x  1015 79.8 
14.6 – 15.0 1.65  x  1015 82.5 
15.1 – 15.5 1.71  x  1015 85.3 
15.6 – 16.0 1.76  x  1015 88.0 
16.1 – 16.5 1.82  x  1015 90.8 
16.6 – 17.0 1.87  x  1015 93.5 
17.1 – 17.5 1.93  x  1015 96.3 
17.6 – 18.0 1.98  x  1015 99.0 
18.1 – 18.5 2.04  x  1015 101.8 
18.6 – 19.0 2.09  x  1015 104.5 
19.1 – 19.5 2.15  x  1015 107.3 
19.6 – 20.0 2.20  x  1015 110.0 
20.1 – 20.5 2.26  x  1015 112.8 
20.6 – 21.0 2.31  x  1015 115.5 

a NOTE: Number of vials per kit and required number of kits is weight-dependent. Dose volume is 
calculated using the upper limit of the patient weight range. 
 
Immunomodulatory regimen 
An immune response to the adeno associated viral vector serotype 9 (AAV9) capsid will occur after 
administration of onasemnogene abeparvovec (see section 4.4). This can lead to elevations in liver 
transaminases, elevations of troponin I, or decreased platelet counts (see sections 4.4 and 4.8). To 
dampen the immune response immunomodulation with corticosteroids is recommended. Where 
feasible, the patient’s vaccination schedule should be adjusted to accommodate concomitant 
corticosteroid administration prior to and following onasemnogene abeparvovec infusion (see 
section  4.5). 
 
Prior to initiation of the immunomodulatory regimen and prior to administration of onasemnogene 
abeparvovec, the patient must be checked for symptoms of active infectious disease of any nature.  
 
Starting 24 hours prior to infusion of onasemnogene abeparvovec it is recommended to initiate an 
immunomodulatory regimen following the schedule below (Table 2). Deviations from these 
recommendations are at the discretion of the treating physician (see section 4.4).  
 
Table 2 pre- and post-infusion immunomodulatory regimen 

Pre-infusion 24 hours prior to onasemnogene 
abeparvovec 

Prednisolone orally 1 mg/kg/day 
(or equivalent) 

Post-infusion 30 days (including the day of administration 
of onasemnogene abeparvovec) 

Prednisolone orally 1 mg/kg/day 
(or equivalent) 

followed by 28 days: 
 
For patients with unremarkable findings 
(normal clinical exam, total bilirubin, and 
whose ALT and AST values are both below 
2 × upper limit of normal (ULN) at the end 
of the 30 days period:   
 
or  

 
 
Tapering of prednisolone (or 
equivalent), e.g. 2 weeks at 
0.5 mg/kg/day and then 2 weeks at 
0.25 mg/kg/day oral prednisolone 
 

For patients with liver function 
abnormalities at the end of the 30 days 
period: continuing until the AST and ALT 
values are below 2 × ULN and all other 
assessments return to normal range, 
followed by tapering over 28 days. 

Systemic corticosteroids 
(equivalent to oral prednisolone 
1 mg/kg/day) 



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 Liver transaminases should be monitored for at least 3 months following 
onasemnogene abeparvovec infusion (see section 4.4) 

Consult expert(s) if patients do not respond adequately to the equivalent of 1 mg/kg/day oral 
prednisolone. 
 
If another corticosteroid is used by the physician in place of prednisolone, similar considerations and 
approach to taper the dose after 30 days should be taken as appropriate. 
 
Special populations 
 
Renal impairment 
The safety and efficacy of onasemnogene abeparvovec have not been established in patients with renal 
impairment and onasemnogene abeparvovec therapy should be carefully considered. A dose 
adjustment should not be considered. 
 
Hepatic impairment 
Onasemnogene abeparvovec has not been studied in patients with hepatic impairment. Onasemnogene 
abeparvovec should not be infused unless elevated bilirubin is associated with neonatal jaundice. 
Onasemnogene abeparvovec therapy should be carefully considered in patients with hepatic 
impairment (see sections 4.4 and 4.8). A dose adjustment should not be considered.  
 
0SMN1/1SMN2 genotype 
No dose adjustment should be considered in patients with a bi-allelic mutation of the SMN1 gene and 
only one copy of SMN2 (see section 5.1). 
 
Anti-AAV9 antibodies 
No dose adjustment should be considered in patients with baseline anti-AAV9 antibody titres above 
1:50 (see section 4.4). 
 
Paediatric population 
The safety and efficacy of onasemnogene abeparvovec in premature neonates before reaching full-
term gestational age have not been established. No data are available. Administration of 
onasemnogene abeparvovec should be carefully considered because concomitant treatment with 
corticosteroids may adversely affect neurological development.  
 
There is limited experience in patients 2 years of age and older or with body weight above 13.5 kg. 
The safety and efficacy of onasemnogene abeparvovec in these patients have not been established. 
Currently available data are described in section 5.1. A dose adjustment should not be considered (see 
Table 1). 
 
Method of administration  
 
For intravenous use. 
 
Onasemnogene abeparvovec is administered as a single-dose intravenous infusion. It should be 
administered with the syringe pump administered as a single intravenous infusion with a slow infusion 
of approximately 60 minutes. It must not be administered as an intravenous push or bolus. 
 
Insertion of a secondary (‘back-up’) catheter is recommended in case of blockage in the primary 
catheter. Following completion of infusion, the line should be flushed with saline. 
 
For instructions on dilution of the product before administration, see section 6.6 
 
Precautions to be taken before handling or administering the medicinal product 
This medicinal product contains a genetically-modified organism. Personal protective equipment (to 
include laboratory coat, safety glasses and gloves) should be worn while preparing or administering 
onasemnogene abeparvovec (see sections 6.6). For instructions on the preparation, handling, 



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accidental exposure to and disposal of the medicinal product, including proper handling of bodily 
waste see 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Pre-existing immunity against AAV9 
Anti-AAV9 antibody formation can take place after natural exposure. There have been several studies 
on the prevalence of AAV9 antibodies in the general population that show low rates of prior exposure 
to AAV9 in the paediatric population. Patients should be tested for the presence of AAV9 antibodies 
prior to infusion with onasemnogene abeparvovec. Retesting may be performed if AAV9 antibody 
titres are reported as above 1:50. It is not yet known whether or under what conditions onasemnogene 
abeparvovec can be safely and effectively administered in the presence of anti-AAV9 antibodies 
above 1:50 (see sections 4.2 and 5.1). 
 
Advanced SMA 
Since SMA results in progressive and non-reversible damage to motor neurons, the benefit of 
onasemnogene abeparvovec in symptomatic patients depends on the degree of disease burden at the 
time of treatment, with earlier treatment resulting in potential higher benefit. While advanced 
symptomatic SMA patients will not achieve the same gross motor development as unaffected healthy 
peers they may clinically benefit from gene replacement therapy, dependent on the advancement of 
disease at the time of treatment (see section 5.1). 
 
The treating physician should consider that the benefit is seriously reduced in patients with profound 
muscle weakness and respiratory failure, patients on permanent ventilation, and patients not able to 
swallow.  
 
The benefit/risk profile of onasemnogene abeparvovec in patients with advanced SMA, kept alive 
through permanent ventilation and without the ability to thrive is not established. 
 
Immunogenicity 
An immune response to the adeno associated viral vector serotype 9 (AAV9) capsid will occur after 
infusion of onasemnogene abeparvovec, including antibody formation against the AAV9 capsid 
despite the immunomodulatory regimen recommended in section 4.2, and T-cell mediated immune 
response. 
 
Systemic immune response, including immune-mediated hepatotoxicity, has been reported in the 
onasemnogene abeparvovec clinical program and may require adjustment of immunomodulatory 
regimen including longer duration or increased dose. Refer to section 4.2 for immunomodulatory 
regimen, to the sub-sections hepatic injury and immunomodulatory regimen below for details. 
 
Hepatic injury 
 
• Administration of AAV vector may result in transaminase elevations, which may be serious. 
• Acute serious liver injury has occurred (see section 4.8). 
• Patients with pre-existing liver impairment or acute hepatic viral infection may be at higher risk 

of liver injury. 



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• Prior to infusion, liver function of all patients should be assessed by clinical examination and 
laboratory testing (e.g., hepatic aminotransferases AST and ALT, and total bilirubin (see 
section 4.2)).  

• In order to mitigate potential transaminase elevations, a systemic corticosteroid should be 
administered to all patients before and after onasemnogene abeparvovec infusion (see 
section 4.2). 

• Liver function should be monitored for at least 3 months after infusion.  
• The risks and benefits of infusion with onasemnogene abeparvovec in pre-existent hepatic 

impairment should be weighed carefully against the risks of not treating the patient.  
 
AST/ALT/bilirubin should be assessed weekly for 30 days and every two weeks for an additional 
60 days post administration of onasemnogene abeparvovec through the end of the corticosteroid taper, 
or longer if needed. Tapering of prednisolone should not be considered until AST/ALT are less than 
2x ULN.  
 
Thrombocytopenia  
Transient decreases in platelet counts, some of which met the criteria for thrombocytopenia, were 
observed in onasemnogene abeparvovec clinical trials. In most cases, the lowest platelet value 
occurred the first week following onasemnogene abeparvovec infusion. Platelet counts should be 
obtained before onasemnogene abeparvovec infusion and monitored on a regular basis afterwards, 
weekly for the first month and every other week for the second and third months until platelet counts 
return to baseline. 
 
Elevated troponin-I 
Increases in cardiac troponin-I levels following infusion with onasemnogene abeparvovec were 
observed. Elevated troponin-I levels found in some patients may indicate potential myocardial tissue 
injury. Based on these findings and the observed cardiac toxicity in mice, troponin-I levels should be 
obtained before onasemnogene abeparvovec infusion and monitored for at least 3 months following 
onasemnogene abeparvovec infusion or until levels return to within normal reference range for SMA 
patients. Consider consultation with a cardiac expert as needed.  
 
Immunomodulatory regimen 
Immunomodulatory treatment should not be initiated concurrently to active infections, either acute 
(such as acute respiratory infections or acute hepatitis) or uncontrolled chronic (such as chronic active 
hepatitis B) (see sections 4.2 and 4.4).  
 
The immunomodulatory regimen (see section 4.2) might also impact the immune response to 
concurrent (respiratory) infections, potentially resulting in more severe clinical courses of the 
concurrent infection. Added caution is advised regarding the timing of onasemnogene abeparvovec 
dosing in the presence of prodrome or resolving (viral) illness. Increased vigilance in the diagnosis and 
active management of (viral) respiratory infection is recommended. Seasonal prophylactic treatments, 
that prevent respiratory syncytial virus (RSV) infections, are recommended and should be up to date. 
Where feasible, the patient’s vaccination schedule should be adjusted to accommodate concomitant 
corticosteroid administration prior to and following onasemnogene abeparvovec infusion (see 
section 4.5). 
 
The treating physician should be aware of the possibility of adrenal insufficiency related to longer 
duration of treatment with corticosteroids which might impact the proposed immunomodulatory 
regimen.  
 
Shedding 
Temporary onasemnogene abeparvovec shedding occurs, primarily through bodily waste. Caregivers 
and patient families should be advised on the following instructions for the proper handling of patient 
stools: 
• good hand-hygiene is required when coming into direct contact with patient bodily waste for a 

minimum of 1 month after onasemnogene abeparvovec treatment.   
• Disposable diapers can be sealed in double plastic bags and disposed of in household waste. 



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Sodium content 
This medicinal product contains 4.6 mg sodium per mL, equivalent to 0.23% of the WHO 
recommended maximum daily intake of 2 g sodium for an adult. Each 5.5 mL vial contains 25.3 mg 
sodium, and each 8.3 mL vial contains 38.2 mg sodium.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed.  
 
Experience with use of onasemnogene abeparvovec in patients receiving hepatotoxic medication or 
using hepatotoxic substances is limited. Safety of onasemnogene abeparvovec in these patients have 
not been established.  
 
Experience with use of concomittant 5q SMA targeting agents is limited. 
 
Vaccinations 
Where feasible, the patient’s vaccination schedule should be adjusted to accommodate concomitant 
corticosteroid administration prior to and following onasemnogene abeparvovec infusion (see 
sections 4.2 and 4.4). Seasonal RSV prophylaxis is recommended (see section 4.4). Live vaccines, 
such as MMR and varicella, should not be administered to patients on an immunosuppressive steroid 
dose (i.e., ≥ 2 weeks of daily receipt of 20 mg or 2 mg/kg body weight of prednisolone or equivalent).  
 
4.6 Fertility, pregnancy and lactation 
 
Human data on use during pregnancy or lactation are not available and animal fertility or reproduction 
studies have not been performed. 
 
4.7 Effects on ability to drive and use machines 
 
Onasemnogene abeparvovec has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most frequently reported adverse reaction following administration was transient hepatic 
transaminase increase (12.4%) and vomiting (8.2%), see section 4.4.  
 
Tabulated list of adverse reactions 
The adverse reactions identified with onasemnogene abeparvovec in all patients treated with 
intravenous infusion with a causal association to treatment are presented in Table 3. Adverse reactions 
are classified according to MedDRA system organ classification and frequency. Frequency categories 
are derived according to the following conventions: very common (≥1/10); common (≥1/100 to 
<1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not 
known (cannot be estimated from the available data). Within each frequency grouping, adverse 
reactions are presented in order of decreasing seriousness. 
 
Table 3 Tabulated list of adverse reactions to onasemnogene abeparvovec  

Adverse Reactions by MedDRA SOC/PT and Frequency 
Blood and lymphatic system disorders 

Common  Thrombocytopenia 
Gastrointestinal disorders 

Common Vomiting 
General disorders and administration site conditions 

Common Pyrexia 
Investigations 

Very Common Transaminases increased  



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Adverse Reactions by MedDRA SOC/PT and Frequency 
Common Aspartate aminotransferase increased, alanine aminotransferase increased, 

troponin-I increased 
 
Description of selected adverse reactions 
 
Hepatobiliary disorders 
Elevated transaminases greater than 2 times ULN were reported in up to 12% of patients treated at the 
recommended dose and were considered study-drug related. Two patients had AST and ALT 
elevations of > 20 × ULN (one of these patients was experiencing a viral infection). These patients 
were clinically asymptomatic, did not exhibit jaundice or a clinically significant elevation of bilirubin 
and did not meet Hy’s Law criteria. Serum transaminase elevations resolved with prednisolone 
treatment (see sections 4.2 and 4.4), and patients recovered without clinical sequelae.  
 
Outside of clinical trials, a case of acute serious liver injury was reported with onasemnogene 
abeparvovec where the patient was continuing treatment with nusinersen and had AST and ALT 
elevations of > 3 × ULN before treatment with onasemnogene abeparvovec. The patient recovered 
with additional steroid therapy.  
 
Transient thrombocytopenia 
Transient decreases from baseline in mean platelet counts (4.1%) were observed at multiple time 
points post-dose and normally resolved within two weeks. Decreases in platelet counts were more 
prominent during the first week of treatment. No patients had clinical symptoms associated with 
decreased platelets. (see section 4.4). 
 
Increases of troponin-I levels 
Increases in cardiac troponin-I levels (3.1%) up to 0.2 mcg/L following onasemnogene abeparvovec 
infusion were observed. In the clinical trial program, there were no clinically apparent cardiac findings 
observed following administration of onasemnogene abeparvovec (see section 4.4). 
 
Immunogenicity 
Pre- and post-gene therapy titres of anti-AAV9 antibodies were measured in the clinical studies 
(see section 4.4). All patients that received onasemnogene abeparvovec had anti-AAV9 titres at or 
below 1:50 before treatment. Mean increases from baseline in AAV9 titre were observed in all patients 
at all but 1 time point for antibody titre levels to AAV9 peptide, reflecting normal response to non-self 
viral antigen. Some patients experienced AAV9 titres exceeding the level of quantification, however 
most of these patients did not have potentially clinically significant adverse reactions. Thus, no 
relationship has been established between high anti-AAV9 antibody titres and the potential for adverse 
reactions or efficacy parameters. 
 
In the AVXS-101-CL-101 clinical study, 16 patients were screened for anti-AAV9 antibody titre: 
13 had titres less than 1:50 and were enrolled in the study; three patients had titres greater than 1:50, 
two of whom were retested following cessation of breast-feeding and their titres were measured at less 
than 1:50 and both were enrolled in the study. There is no information on whether breastfeeding 
should be restricted in mothers who may be seropositive for anti-AAV9 antibodies. Patients all had 
less than or equal to 1:50 AAV9 antibody titre prior to treatment with onasemnogene abeparvovec and 
subsequently demonstrated an expected increase in anti-AAV9 antibody titres to at least 1:102,400 and 
up to greater than 1:819,200.  
 
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.  
In addition, the observed incidence of antibody (including neutralising antibody) positivity in an assay 
may be influenced by several factors including assay methodology, sample handling, timing of sample 
collection, concomitant medicinal products and underlying disease. 
 
No onasemnogene abeparvovec-treated patient demonstrated an immune response to the transgene. 
 



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Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
No data from clinical studies are available regarding overdose of onasemnogene abeparvovec. 
Adjustment of the dose of prednisolone, close clinical observation and monitoring of laboratory 
parameters (including clinical chemistry and haematology) for systemic immune response are 
recommended (see section 4.4). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other drugs for disorders of the musculo-skeletal system, ATC code: 
M09AX09 
 
Mechanism of action 
Onasemnogene abeparvovec is a gene therapy designed to introduce a functional copy of the survival 
motor neuron gene (SMN1) in the transduced cells to address the monogenic root cause of the disease. 
By providing an alternative source of SMN protein expression in motor neurons, it is expected to 
promote the survival and function of tranduced motor neurons.  
 
Onasemnogene abeparvovec is a non-replicating recombinant AAV vector that utilizes AAV9 capsid 
to deliver a stable, fully functional human SMN transgene. The ability of the AAV9 capsid to cross the 
blood brain barrier and transduce motor neurons has been demonstrated. The SMN1 gene present in 
onasemnogene abeparvovec is designed to reside as episomal DNA in the nucleus of transduced cells 
and is expected to be stably expressed for an extended period of time in post-mitotic cells. The 
AAV9 virus is not known to cause disease in humans. The transgene is introduced to target cells as a 
self-complementary double-stranded molecule. Expression of the transgene is driven by a constitutive 
promoter (cytomegalovirus enhanced chicken β-actin hybrid), which results in continuous and 
sustained SMN protein expression. Proof of the mechanism of action has been supported by non-
clinical studies and by human biodistribution data. 
 
Clinical efficacy and safety 
 
AVXS-101-CL-303 Phase 3 Study in Patients with Type 1 SMA 
 
AVXS-101-CL-303 (Study 303) is a Phase 3 open-label, single-arm, single-dose study of intravenous 
administration of onasemnogene abeparvovec at the therapeutic dose (1.1 × 1014 vg/kg). Twenty two 
patients were enrolled with Type 1 SMA and 2 copies of SMN2. Patient ages at administration ranged 
from 0.5 to 5.9 months. Of the 22 enrolled patients, three patients discontinued the study of which two 
patients had an event (death or permanent ventilation) leading to 90.9% (95% CI: 79.7%, 100.0%) 
event-free survival (alive without permanent ventilation) at 14 months of age, see Figure 1.  
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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Figure 1 Time (days) to death or permanent ventilation pooled from onasemnogene 
abeparvovec IV studies (CL-101, CL-302, CL-303, CL-304-2 copy cohort)  

 
 
PNCR = Pediatric Neuromuscular Clinical Research natural history cohort 
NeuroNext = Network for Excellence in Neuroscience Clinical Trials natural history cohort 
* AVXS-101-CL-302 is an ongoing Phase 3 multicenter, open-label, single-arm, single-dose study of 
AVXS-101 (gene replacement therapy) in patients with SMA Type 1 with 1 or 2 copies of the SMN2 
gene similar to study AVXS-101-CL-303. The average age of the patients in the study at time of the 
31 December 2019 data cutoff is 10.62 months (range 1.8 to 15.4 months).   
 
For the 14 patients in Study CL-303 that achieved the milestone of independent sitting for at least 
30 seconds, the median age when this milestone was first demonstrated was 12.5 months (range 9.2 to 
18.6 months.  Thirteen patients confirmed the milestone of independent sitting for at least 30 seconds 
at the 18 month visit (co-primary endpoint, p<0.0001).  One patient achieved the milestone of sitting 
independently for 30 seconds at 16 months of age, but this milestone was not confirmed at the 
Month 18 visit. The video-confirmed developmental milestones for patients in Study CL-303 are 
summarised in Table 4. Three patients did not achieve any motor milestones (13.6%) and six patients 
(27.2%) achieved head control as the maximum motor milestone before the 18 months of age final 
study visit.   
 
Table 4 Median time to video document achievement of motor milestones Study 303 
Video documented 
milestone 

Number of patients 
achieving milestone 
n/N (%) 

Median age to 
the milestone 
achievement  
(Months) 

95% Confidence interval 

Head control 17/20 (85) 6.8 (4.77, 7.17) 
Rolls from back to sides 13/22 (59) 11.5 (7.77, 14.53) 
Sits without support for 
30 seconds (Bayley) 

14/22 (64) 12.5  (10.17, 15.20) 

12 12 12 12 12 12 0
33 33 30 17 0
22 22 21 20 0
14 14 7 5 0
16 14 7 4 2 1 0
23 21 13 6 5 2 0

0 5 10 15 20 25 30

Age (Months)

0.0

0.2

0.4

0.6

0.8

1.0
Su

rv
iva

l P
ro

ba
bil

ity

101/Coh 2
302
303

304/2 Copy
NeuroNext

PNCR

PNCRNeuroNext304/2 Copy
303302101/Coh 2

Study

  
With Number of Subjects at Risk

12 12 12 12 12 12 0
33 33 30 17 0
22 22 21 20 0
14 14 7 5 0
16 14 7 4 2 1 0
23 21 13 6 5 2 0

0 5 10 15 20 25 30

Age (Months)

0.0

0.2

0.4

0.6

0.8

1.0
Su

rv
iva

l P
ro

ba
bil

ity

101/Coh 2
302
303

304/2 Copy
NeuroNext

PNCR

PNCRNeuroNext304/2 Copy
303302101/Coh 2

Study

+ Censored

  
With Number of Subjects at Risk

Age (months) 

Pr
ob

ab
ili

ty
 o

f e
ve

nt
-fr

ee
 su

rv
iv

al
 

* 



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Sitting without support 
for at least 10 seconds 
(WHO) 

14/22 (64) 13.9 (11.00, 16.17) 

*2 patients were reported to have Head Control by clinician assessment at baseline. 
 
One patient (4.5%) could also walk with assistance at 12.9 months. Based on the natural history of the 
disease, patients who met the study entry criteria would not be expected to attain the ability to sit 
without support.  
 
Motor function improvements were also observed as measured by the Children’s Hospital of 
Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), see Figure 2. Twenty-one 
patients (95.5%) achieved a CHOP-INTEND score ≥ 40, 14 (64%) had achieved a CHOP-INTEND 
score ≥ 50, and 5 patients (23%) had achieved a CHOP-INTEND score ≥ 60.  Patients with untreated 
SMA Type 1 almost never achieve a CHOP-INTEND score ≥ 40. Motor milestone achievement was 
observed in some patients despite plateauing of CHOP-INTEND. No clear correlation was observed 
between CHOP-INTEND scores and motor milestone achievement.  
 
Figure 2  CHOP-INTEND Motor Function Scores Study 303 

 
 
AVXS-101-CL-101 Phase 1 Study in Patients with Type 1 SMA 
 
The results seen in Study 303 are supported by study AVXS-101-CL-101 (Phase 1 study in Type 1 
SMA, Study 101) in which onasemnogene abeparvovec was administered as a single intravenous 
infusion in 12 patients from 2.6 kg to 8.5 kg (0.9 to 7.9 months of age). At 14 months of age, all 
treated patients were event free; i.e. survived without permanent ventilation, compared to 25% in the 
natural history cohort. At the end of the study (24 months post dose), all treated patients were event 
free, compared to less than 8% in the natural history, see Figure 1. 
 
At 24 months of follow up post dose, 10 out of 12 patients were able to sit without support for 
≥ 10 seconds, 9 patients were able to sit without support for ≥ 30 seconds and 2 patients were able to 
stand and walk without assistance. One out of 12 patients did not achieve head control as the 
maximum motor milestone before the age of 24 months. Ten of 12 patients from Study CL-101 who 
received the proposed therapeutic dose of onasemnogene abeparvovec continue to be followed in a 
long-term study (for up to 5.7 years after dosing) and all have either maintained all previously attained 
milestones or even gained new milestones including such as sitting with support, stand with assistance 
and walk alone. Four of the 10 patients received concomitant nusinersen treatment at some point 
during the long-term study. Maintenance of efficacy and achievement of milestones can therefore not 

Age (months) 

C
H

O
P 

IN
TE

N
D

 S
co

re
 

 



13 

be solely attributed to onasemnogene abeparvovec in all patients. The milestone of stand with 
assistance was newly acquired by two patients who were not receiving nusinersen. 
 
AVXS-101-CL-304 Phase 3 Study in Patients with pre-symptomatic SMA 
Study CL-304 is an ongoing, global, Phase 3, open-label, single-arm, single-dose, multicenter study of 
IV AVXS-101 in pre-symptomatic newborn patients up to 6 weeks of age with 2 (cohort 1, n=14) or 
3 (cohort 2, n=15) copies of SMN2.  
 
Cohort 1 
At the time of the last study visit prior to 31 December 2019, treated patients with 2 copies of SMN2 
were between 6 months and 18.6 months of age and had been in the study for an average of 
10.5 months (range: 5.1 to 18.0 months). All patients were alive and free of permanent ventilation.  
 
Eight patients achieved independent sitting for at least 30 seconds, at ages ranging from 6.4 to 
11.8 months, with 7 of these 8 (87.5%) achieving independent sitting prior to the 9.2 months of age, 
the 99th percentile for development of this milestone. Four patients achieved the milestone of walking 
alone (28.6%).  Twelve (12) patients (85.7%) have achieved CHOP-INTEND scores ≥ 60 as of the 
31 December 2019 data cutoff. 
 
Cohort 2 
At the time of the last study visit prior to 31 December 2019, treated patients with 3 copies of SMN2 
were between 3.3 and 15.1 months of age and had been in the study for an average of 8.74 months 
(range: 2 to 13.9 months). All patients were alive and free of permanent ventilation.  Ten of 
15 patients were able to sit without support for at least 30 seconds, 4 patients were able to stand alone 
without support for at least 3 seconds, and 2 patients walk at least five steps independently.  
The follow up duration is too short to assess the development of patients treated with AVXS-101 
treatment compared to the natural history of patients with 3 SMN2 copies, who have a heterogeneous 
clinical presentation. Therefore, no definitive conclusions about the benefit in this patient population 
can be drawn at this moment. 
 
Onasemnogene abeparvovec has not been studied in patients with a bi-allelic mutation of the 
SMN1 gene and only one copy of SMN2 in clinical trials.  
 
This medicinal product has been authorised under a so-called ‘conditional approval’ scheme. This 
means that further evidence on this medicinal product is awaited. The European Medicines Agency 
will review new information on this medicinal product at least every year and this SmPC will be 
updated as necessary. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
onasemnogene abeparvovec in one or more subsets of the paediatric population in Spinal Muscular 
Atrophy for the granted indication (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Onasemnogene abeparvovec vector shedding studies, which assess the amount of vector eliminated 
from the body through saliva, urine and faeces were performed. 
 
Onasemnogene abeparvovec was detectable in shedding samples post-infusion. Clearance of 
onasemnogene abeparvovec was primarily via faeces and the majority is cleared within 30 days after 
dose administration. Onasemnogene abeparvovec concentrations in urine and saliva were 0.1% to 
0.01% of initial concentration in the body at day 1 post infusion and dropped thereafter. 
 
Biodistribution was evaluated in two patients who died 5.7 months and 1.7 months, respectively, after 
infusion of onasemnogene abeparvovec at the dose of 1.1 x 1014 vg/kg. Both cases showed that the 
highest levels of vector DNA were found in the liver. Vector DNA was also detected in the spleen, 
heart, pancreas, inguinal lymph node, skeletal muscles, peripheral nerves, kidney, lung, intestines, 
spinal cord, brain, and thymus. Immunostaining for SMN protein showed generalized SMN expression 



14 

in spinal motor neurons, neuronal and glial cells of the brain, and in the heart, liver, skeletal muscles, 
and other tissues evaluated.  
 
5.3 Preclinical safety data 
 
Following intravenous administration in neonatal mice, vector and transgene were widely distributed 
with the highest expression generally observed in heart and liver, and substantial expression in the 
brain and spinal cord.  In pivotal 3 month mouse toxicology studies, the main target organs of toxicity 
identified were the heart and liver.  Onasemnogene abeparvovec-related findings in the ventricles of 
the heart were comprised of dose-related inflammation, oedema and fibrosis. In the atria of the heart, 
inflammation, thrombosis, myocardial degeneration/necrosis and fibroplasia were observed.  Liver 
findings were comprised of hepatocellular hypertrophy, Kupffer cell activation, and scattered 
hepatocellular necrosis.  A No Adverse Effect Level (NoAEL) was not identified for onasemnogene 
abeparvovec in the mouse as ventricular myocardial inflammation/oedema/fibrosis and atrial 
inflammation were observed at the lowest dose tested (1.5 × 1014 vg/kg). This dose is regarded the 
Maximum Tolerated Dose and approximately 1.4 fold the recommended clinical dose. Onasemnogene 
abeparvovec-related mortality was, in the majority of mice, associated with atrial thrombosis, and 
observed at 2.4 × 1014 vg/kg. The cause of the mortality in the rest of the animals was undetermined, 
although microscopic degeneration/regeneration in the hearts of these animals was found.  
 
Genotoxicity, carcinogenicity and reproduction toxicity studies have not been conducted with 
onasemnogene abeparvovec.  
 
In a toxicology study conducted in young adult non-human primates, administration of a single dose of 
3x1013 vg/NHP (median dose 1.08x1013 vg/kg) onasemnogene abeparvovec intrathecally with 
Trendelenburg position, without corticosteroid treatment, resulted in minimal to marked mononuclear 
cell inflammation (primarily lymphocytes) in some dorsal root ganglia from all examined spinal cord 
levels, with neuronal satellitosis, neuronal necrosis, or complete neuronal loss with rare 
mineralization. The clinical relevance of this finding is unknown. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tromethamine 
Magnesium chloride 
Sodium chloride 
Poloxamer 188 
Hydrochloric acid (for pH adjustment) 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product should not be mixed with other 
medicinal products. 
 
6.3 Shelf life 
 
1 year 
 
After thawing 
Once thawed, the medicinal product should not be re-frozen and may be stored refrigerated at 2°C to 
8°C in the original carton for 14 days. 
 
Once the dose volume is drawn into the syringe it must be infused within 8 hours.  Discard the vector 
containing syringe if not infused within the 8 hour timeframe. 



15 

6.4 Special precautions for storage 
 
Store and transport frozen (≤ -60°C). 
Store in a refrigerator (2 -8°C) immediately upon receipt.  
Store in the original carton. 
For storage conditions after thawing of the medicinal product, see section 6.3. 
The date of receipt should be marked on the original carton before the product is stored in the 
refrigerator. 
 
6.5 Nature and contents of container 
 
Onasemnogene abeparvovec is supplied in a vial (10 mL polymer crystal zenith) with stopper (20 mm 
chlorobutyl rubber) and seal (aluminum, flip-off) with a coloured cap (plastic), in two different vial fill 
volume sizes, either 5.5 mL or 8.3 mL. 
 
The dose of onasemnogene abeparvovec and exact number of vials required for each patient is 
calculated according to the patient’s weight (see section 4.2 and Table 5 below). 
 
Table 5 Carton/kit configurations 

Patient weight (kg) 5.5 mL viala 8.3 mL vialb Total vials per carton 
2.6 – 3.0 0 2 2 
3.1 – 3.5 2 1 3 
3.6 – 4.0 1 2 3 
4.1 – 4.5 0 3 3 
4.6 – 5.0 2 2 4 
5.1 – 5.5 1 3 4 
5.6 – 6.0 0 4 4 
6.1 – 6.5 2 3 5 
6.6 – 7.0 1 4 5 
7.1 – 7.5 0 5 5 
7.6 – 8.0 2 4 6 
8.1 – 8.5 1 5 6 
8.6 – 9.0 0 6 6 
9.1 – 9.5 2 5 7 
9.6 – 10.0 1 6 7 

10.1 – 10.5 0 7 7 
10.6 – 11.0 2 6 8 
11.1 – 11.5 1 7 8 
11.6 – 12.0 0 8 8 
12.1 – 12.5 2 7 9 
12.6 – 13.0 1 8 9 
13.1 – 13.5 0 9 9 
13.6 – 14.0 2 8 10 
14.1 – 14.5 1 9 10 
14.6 – 15.0 0 10 10 
15.1 – 15.5 2 9 11 
15.6 – 16.0 1 10 11 
16.1 – 16.5 0 11 11 



16 

Patient weight (kg) 5.5 mL viala 8.3 mL vialb Total vials per carton 
16.6 – 17.0 2 10 12 
17.1 – 17.5 1 11 12 
17.6 – 18.0 0 12 12 
18.1 – 18.5 2 11 13 
18.6 – 19.0 1 12 13 
19.1 – 19.5 0 13 13 
19.6 – 20.0 2 12 14 
20.1 – 20.5 1 13 14 
20.6 – 21.0 0 14 14 

a Vial nominal concentration is 2 × 1013 vg/mL and contains an extractable volume of not less 
than 5.5 mL. 

b Vial contains nominal concentration is 2 × 1013 vg/mL and an extractable volume of not less 
than 8.3 mL. 

 
6.6 Special precautions for disposal and other handling 
 
This medicinal product contains genetically-modified organisms. Appropriate precautions for the 
handling, disposal or accidental exposure of onasemnogene abeparvovec should be followed: 
• The onasemnogene abeparvovec syringe should be handled aseptically under sterile conditions.  
• Personal protective equipment (to include gloves, safety goggles, laboratory coat and sleeves) 

should be worn while handling or administering onasemnogene abeparvovec. Personnel should 
not work with onasemnogene abeparvovec if skin is cut or scratched. 

• All spills of onasemnogene abeparvovec must be wiped with absorbent gauze pad and the spill 
area must be disinfected using a bleach solution followed by alcohol wipes. All clean up 
materials must be double bagged and disposed of per local guidelines for handling of biological 
waste. 

• All materials that may have come in contact with onasemnogene abeparvovec (e.g. vial, all 
materials used for injection, including sterile drapes and needles) must be disposed of in 
accordance with local guidelines on handling of biological waste. 

• Accidental exposure to onasemnogene abeparvovec must be avoided.  In the event of exposure 
to skin, the affected area must be thoroughly cleaned with soap and water for at least 
15 minutes. In the event of exposure to eyes, the affected area must be thoroughly flushed with 
water for at least 15 minutes. 

 
Receipt and thawing vials 
• Vials will be transported frozen (≤-60ºC).  Upon receipt vials should be refrigerated at 

2°C to 8°C immediately, and in the original carton.  Onasemnogene abeparvovec therapy should 
be initiated within 14 days of receipt of vials.  

• Vials must be thawed before use. Do not use onasemnogene abeparvovec unless thawed. 
• For packaging configurations containing up to 9 vials, product will be thawed after 

approximately 12 hours in the refrigerator. For packaging configurations containing up to 
14 vials, product will be thawed after approximately 16 hours in the refrigerator. Alternatively, 
and for immediate use, thawing may be performed at room temperature. 

• For packaging configurations containing up to 9 vials, thawing will occur from frozen state after 
approximately 4 hours at room temperature (20°C to 25°C). For packaging configurations 
containing up to 14 vials, thawing will occur from frozen state after approximately 6 hours at 
room temperature (20°C to 25°C) 

• Before drawing the dose volume into the syringe, gently swirl the thawed product.  Do NOT 
shake. 

• Do not use this medicine if you notice any particles or discolouration once the frozen product 
has thawed and prior to administration. 

• Once thawed, the medicinal product should not be re-frozen. 



17 

• After thawing, onasemnogene abeparvovec should be given as soon as possible. Once the dose 
volume is drawn into the syringe it must be infused within 8 hours.  Discard the 
vector-containing syringe if not infused within the 8-hour timeframe. 

 
Administration of onasemnogene abeparvovec to the patient 
• To administer onasemnogene abeparvovec, draw the entire dose volume into the syringe. 

Remove any air in the syringe and prepare the infusion bag before intravenous infusion through 
a venous catheter.   

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
guidelines on handling of biological waste. 
 
Temporary onasemnogene abeparvovec shedding may occur, primarily through bodily waste.  
Caregivers and patient families should be advised on the following instructions for the proper handling 
of patient bodily fluids and waste:   
• Good hand-hygiene (wearing protective gloves and washing hands thoroughly afterwards with 

soap and warm running water, or an alcohol-based hand sanitiser) is required when coming into 
direct contact with patient bodily fluids and waste for a minimum of 1 month after 
onasemnogene abeparvovec treatment.   

• Disposable diapers should be sealed in double plastic bags and can be disposed of in household 
waste. 

 
 
7. MARKETING AUTHORISATION HOLDER 
 
AveXis EU Limited 
Block B, The Crescent Building 
Northwood, Santry 
Dublin 9 
D09 C6X8  
Ireland  
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/20/1443/001 
EU/1/20/1443/002 
EU/1/20/1443/003 
EU/1/20/1443/004 
EU/1/20/1443/005 
EU/1/20/1443/006 
EU/1/20/1443/007 
EU/1/20/1443/008 
EU/1/20/1443/009 
EU/1/20/1443/010 
EU/1/20/1443/011 
EU/1/20/1443/012 
EU/1/20/1443/013 
EU/1/20/1443/014 
EU/1/20/1443/015 
EU/1/20/1443/016 
EU/1/20/1443/017 
EU/1/20/1443/018 
EU/1/20/1443/019 
EU/1/20/1443/020 
EU/1/20/1443/021 
EU/1/20/1443/022 



18 

EU/1/20/1443/023 
EU/1/20/1443/024 
EU/1/20/1443/025 
EU/1/20/1443/026 
EU/1/20/1443/027 
EU/1/20/1443/028 
EU/1/20/1443/029 
EU/1/20/1443/030 
EU/1/20/1443/031 
EU/1/20/1443/032 
EU/1/20/1443/033 
EU/1/20/1443/034 
EU/1/20/1443/035 
EU/1/20/1443/036 
EU/1/20/1443/037 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.  

  

http://www.ema.europa.eu/


19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 
BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 
E. SPECIFIC OBLIGATION TO COMPLETE POST-

AUTHORISATION MEASURES FOR THE CONDITIONAL 
MARKETING AUTHORISATION 



20 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer(s) of the biological active substance(s) 
AveXis, Inc.  
1940 USG Drive  
Libertyville  
IL 60048 
United States 
 
Name and address of the manufacturer(s) responsible for batch release 
Almac Pharma Services (Ireland) Limited  
Finnabair Industrial Estate 
Dundalk 
Co. Louth 
A91 P9KD 
Ireland 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 
6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
• Obligation to conduct post-authorisation measures  
 
The MAH shall complete, within the stated timeframe, the below measures: 
 



21 

Description Due date 
Non-interventional post-authorisation efficacy study (PAES): 
In order to further characterise and contextualise the outcomes of patients with a 
diagnosis of SMA, including long-term safety and efficacy of Zolgensma, the 
MAH should conduct and submit the results of a prospective observational 
registry AVXS-101-RG-001 according to an agreed protocol. 

Interim reports 
to be submitted 
with annual 
renewal. Final 
study report 
2038.  

The applicant should perform a further evaluation of the finished product 
specifications when primary and key secondary endpoint data from additional 
patients with 2 copies of SMN2 are available (i.e. completion of CL-302 and 
CL-304 cohort 1). Based on this evaluation, it should be determined whether 
tightening of the release specification limits is needed to improve consistency of 
the batches and ensure optimal clinical outcome. 

Dec 2021 with 
completion of 
Study CL-302 
and Cohort 1 
in Study 
CL-304   

 
 
E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 

FOR THE CONDITIONAL MARKETING AUTHORISATION 
 
This being a conditional marketing authorisation and pursuant to Article 14a(4) of Regulation (EC) No 
726/2004, the MAH shall complete, within the stated timeframe, the following measures: 
 

Description Due date 
Post-authorisation efficacy study (PAES): 
In order to confirm the efficacy and safety and tolerability of a single dose of 
Zolgensma in patients younger than 6 months of age with Spinal Muscular 
Atrophy Type 1 with One or Two SMN2 Copies the MAH should submit final 
data on Study AVXS-101-CL-303 

Final results: 
at first annual 
renewal 

Post-authorisation efficacy study (PAES): 
In order to confirm the efficacy and safety and tolerability of a single dose of 
Zolgensma in patients younger than 6 months of age with Spinal Muscular 
Atrophy Type 1 with One or Two SMN2 Copies the MAH should submit interim 
and final data on Study AVXS-101-CL-302 

Interim results: 
at each annual 
renewal 
 
Final results: 
Aug 2021 

Post-authorisation efficacy study (PAES): 
In order to confirm the efficacy and safety and tolerability of a single dose of 
Zolgensma in genetically diagnosed and pre-symptomatic patients equal or 
younger than 6 weeks of age at time of treatment with SMA with bi-allelic 
deletion of SMN1 with 2 or 3 copies of SMN2, the MAH should submit interim 
and final data on Study AVXS-101-CL-304 

Interim results: 
at each annual 
renewal 
 
Final results: 
Aug 2026 

  



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON – GENERIC LABELLING 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zolgensma 2 x 1013 vector genomes/mL solution for infusion 
onasemnogene abeparvovec 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains onasemnogene abeparvovec equivalent to 2 x 1013 vector genomes/mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains tromethamine, magnesium chloride, sodium chloride, poloxamer 188, hydrochloric acid 
and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for infusion 
8.3 mL vial x 2 
5.5 mL vial x 2, 8.3 mL vial x 1 
5.5 mL vial x 1, 8.3 mL vial x 2 
8.3 mL vial x 3 
5.5 mL vial x 2, 8.3 mL vial x 2 
5.5 mL vial x 1, 8.3 mL vial x 3 
8.3 mL vial x 4 
5.5 mL vial x 2, 8.3 mL vial x 3 
5.5 mL vial x 1, 8.3 mL vial x 4 
8.3 mL vial x 5 
5.5 mL vial x 2, 8.3 mL vial x 4 
5.5 mL vial x 1, 8.3 mL vial x 5 
8.3 mL vial x 6 
5.5 mL vial x 2, 8.3 mL vial x 5 
5.5 mL vial x 1, 8.3 mL vial x 6 
8.3 mL vial x 7 
5.5 mL vial x 2, 8.3 mL vial x 6 
5.5 mL vial x 1, 8.3 mL vial x 7 
8.3 mL vial x 8 
5.5 mL vial x 2, 8.3 mL vial x 7 
5.5 mL vial x 1, 8.3 mL vial x 8 
8.3 mL vial x 9 
5.5 mL vial x 2, 8.3 mL vial x 8 
5.5 mL vial x 1, 8.3 mL vial x 9 
8.3 mL vial x 10 
5.5 mL vial x 2, 8.3 mL vial x 9 
5.5 mL vial x 1, 8.3 mL vial x 10 
8.3 mL vial x 11 
5.5 mL vial x 2, 8.3 mL vial x 10 
5.5 mL vial x 1, 8.3 mL vial x 11 
8.3 mL vial x 12 



25 

5.5 mL vial x 2, 8.3 mL vial x 11 
5.5 mL vial x 1, 8.3 mL vial x 12 
8.3 mL vial x 13 
5.5 mL vial x 2, 8.3 mL vial x 12 
5.5 mL vial x 1, 8.3 mL vial x 13 
8.3 mL vial x 14 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use. 
Single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
Must use within 14 days of receipt.  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store and transport frozen at ≤-60°C. 
Store in a refrigerator 2-8°C immediately upon receipt. 
Store in the original carton. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
This medicine contains genetically-modified organisms. 
Unused medicine or waste material must be disposed of in compliance with the local guidelines on 
handling of biological waste. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AveXis EU Limited 
Block B, The Crescent Building 
Northwood, Santry 
Dublin 9 
D09 C6X8 
Ireland 
 



26 

 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/20/1443/001 – 8.3 mL vial x 2 
EU/1/20/1443/002 – 5.5 mL vial x 2, 8.3 mL vial x 1 
EU/1/20/1443/003 – 5.5 mL vial x 1, 8.3 mL vial x 2 
EU/1/20/1443/004 – 8.3 mL vial x 3 
EU/1/20/1443/005 – 5.5 mL vial x 2, 8.3 mL vial x 2 
EU/1/20/1443/006 – 5.5 mL vial x 1, 8.3 mL vial x 3 
EU/1/20/1443/007 – 8.3 mL vial x 4 
EU/1/20/1443/008 – 5.5 mL vial x 2, 8.3 mL vial x 3 
EU/1/20/1443/009 – 5.5 mL vial x 1, 8.3 mL vial x 4 
EU/1/20/1443/010 – 8.3 mL vial x 5 
EU/1/20/1443/011 – 5.5 mL vial x 2, 8.3 mL vial x 4 
EU/1/20/1443/012 – 5.5 mL vial x 1, 8.3 mL vial x 5 
EU/1/20/1443/013 – 8.3 mL vial x 6 
EU/1/20/1443/014 – 5.5 mL vial x 2, 8.3 mL vial x 5 
EU/1/20/1443/015 – 5.5 mL vial x 1, 8.3 mL vial x 6 
EU/1/20/1443/016 – 8.3 mL vial x 7 
EU/1/20/1443/017 – 5.5 mL vial x 2, 8.3 mL vial x 6 
EU/1/20/1443/018 – 5.5 mL vial x 1, 8.3 mL vial x 7 
EU/1/20/1443/019 – 8.3 mL vial x 8 
EU/1/20/1443/020 – 5.5 mL vial x 2, 8.3 mL vial x 7 
EU/1/20/1443/021 – 5.5 mL vial x 1, 8.3 mL vial x 8 
EU/1/20/1443/022 – 8.3 mL vial x 9 
EU/1/20/1443/023 – 5.5 mL vial x 2, 8.3 mL vial x 8 
EU/1/20/1443/024 – 5.5 mL vial x 1, 8.3 mL vial x 9 
EU/1/20/1443/025 – 8.3 mL vial x 10 
EU/1/20/1443/026 – 5.5 mL vial x 2, 8.3 mL vial x 9 
EU/1/20/1443/027 – 5.5 mL vial x 1, 8.3 mL vial x 10 
EU/1/20/1443/028 – 8.3 mL vial x 11 
EU/1/20/1443/029 – 5.5 mL vial x 2, 8.3 mL vial x 10 
EU/1/20/1443/030 – 5.5 mL vial x 1, 8.3 mL vial x 11 
EU/1/20/1443/031 – 8.3 mL vial x 12 
EU/1/20/1443/032 – 5.5 mL vial x 2, 8.3 mL vial x 11 
EU/1/20/1443/033 – 5.5 mL vial x 1, 8.3 mL vial x 12 
EU/1/20/1443/034 – 8.3 mL vial x 13 
EU/1/20/1443/035 – 5.5 mL vial x 2, 8.3 mL vial x 12 
EU/1/20/1443/036 – 5.5 mL vial x 1, 8.3 mL vial x 13 
EU/1/20/1443/037 – 8.3 mL vial x 14 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 



27 

 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 
  



28 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
OUTER CARTON – VARIABLE DATA (to be printed directly on the outer carton at time of 
packaging) 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION  
 
Zolgensma 2 x 1013 vector genomes/mL solution for infusion 
onasemnogene abeparvovec 
IV 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
EU/1/20/1443/001 – 8.3 mL vial x 2 
EU/1/20/1443/002 – 5.5 mL vial x 2, 8.3 mL vial x 1 
EU/1/20/1443/003 – 5.5 mL vial x 1, 8.3 mL vial x 2 
EU/1/20/1443/004 – 8.3 mL vial x 3 
EU/1/20/1443/005 – 5.5 mL vial x 2, 8.3 mL vial x 2 
EU/1/20/1443/006 – 5.5 mL vial x 1, 8.3 mL vial x 3 
EU/1/20/1443/007 – 8.3 mL vial x 4 
EU/1/20/1443/008 – 5.5 mL vial x 2, 8.3 mL vial x 3 
EU/1/20/1443/009 – 5.5 mL vial x 1, 8.3 mL vial x 4 
EU/1/20/1443/010 – 8.3 mL vial x 5 
EU/1/20/1443/011 – 5.5 mL vial x 2, 8.3 mL vial x 4 
EU/1/20/1443/012 – 5.5 mL vial x 1, 8.3 mL vial x 5 
EU/1/20/1443/013 – 8.3 mL vial x 6 
EU/1/20/1443/014 – 5.5 mL vial x 2, 8.3 mL vial x 5 
EU/1/20/1443/015 – 5.5 mL vial x 1, 8.3 mL vial x 6 
EU/1/20/1443/016 – 8.3 mL vial x 7 
EU/1/20/1443/017 – 5.5 mL vial x 2, 8.3 mL vial x 6 
EU/1/20/1443/018 – 5.5 mL vial x 1, 8.3 mL vial x 7 
EU/1/20/1443/019 – 8.3 mL vial x 8 
EU/1/20/1443/020 – 5.5 mL vial x 2, 8.3 mL vial x 7 
EU/1/20/1443/021 – 5.5 mL vial x 1, 8.3 mL vial x 8 
EU/1/20/1443/022 – 8.3 mL vial x 9 
EU/1/20/1443/023 – 5.5 mL vial x 2, 8.3 mL vial x 8 
EU/1/20/1443/024 – 5.5 mL vial x 1, 8.3 mL vial x 9 
EU/1/20/1443/025 – 8.3 mL vial x 10 
EU/1/20/1443/026 – 5.5 mL vial x 2, 8.3 mL vial x 9 
EU/1/20/1443/027 – 5.5 mL vial x 1, 8.3 mL vial x 10 
EU/1/20/1443/028 – 8.3 mL vial x 11 



29 

EU/1/20/1443/029 – 5.5 mL vial x 2, 8.3 mL vial x 10 
EU/1/20/1443/030 – 5.5 mL vial x 1, 8.3 mL vial x 11 
EU/1/20/1443/031 – 8.3 mL vial x 12 
EU/1/20/1443/032 – 5.5 mL vial x 2, 8.3 mL vial x 11 
EU/1/20/1443/033 – 5.5 mL vial x 1, 8.3 mL vial x 12 
EU/1/20/1443/034 – 8.3 mL vial x 13 
EU/1/20/1443/035 – 5.5 mL vial x 2, 8.3 mL vial x 12 
EU/1/20/1443/036 – 5.5 mL vial x 1, 8.3 mL vial x 13 
EU/1/20/1443/037 – 8.3 mL vial x 14 
 
 
6. OTHER 
 
Patient Weight 
2.6 – 3.0 kg 
3.1 – 3.5 kg 
3.6 – 4.0 kg 
4.1 – 4.5 kg 
4.6 – 5.0 kg 
5.1 – 5.5 kg 
5.6 – 6.0 kg 
6.1 – 6.5 kg 
6.6 – 7.0 kg 
7.1 – 7.5 kg 
7.6 – 8.0 kg 
8.1 – 8.5 kg 
8.6 – 9.0 kg 
9.1 – 9.5 kg 
9.6 – 10.0 kg 
10.1 – 10.5 kg 
10.6 – 11.0 kg 
11.1 – 11.5 kg 
11.6 – 12.0 kg 
12.1 – 12.5 kg 
12.6 – 13.0 kg 
13.1 – 13.5 kg 
13.6 – 14.0 kg 
14.1 – 14.5 kg 
14.6 – 15.0 kg 
15.1 – 15.5 kg 
15.6 – 16.0 kg 
16.1 – 16.5 kg 
16.6 – 17.0 kg 
17.1 – 17.5 kg 
17.6 – 18.0 kg 
18.1 – 18.5 kg 
18.6 – 19.0 kg 
19.1 – 19.5 kg 
19.6 – 20.0 kg 
20.1 – 20.5 kg 
20.6 – 21.0 kg 
 
Date of Receipt: 
 
2D barcode carrying the unique identifier included. 
PC:  
SN:  



30 

NN:  
  



31 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Zolgensma 2 x 1013 vector genomes/mL solution for infusion 
onasemnogene abeparvovec 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5.5 mL 
8.3 mL 
 
 
6. OTHER 
 

  



32 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



33 

Package leaflet: Information for the user 
 

Zolgensma 2 x 1013 vector genomes/mL solution for infusion 
onasemnogene abeparvovec 

 
This medicine is subject to additional monitoring.  This will allow quick identification of new 

safety information.  You can help by reporting any side effects your child may get.  See the end of 
section 4 for how to report side effects. 
 
Read all of this leaflet carefully before your child is given this medicine because it contains 
important information. 
- Keep this leaflet.  You may need to read it again. 
- If you have any further questions, ask your child’s doctor or nurse. 
- If your child gets any side effects, talk to your child’s doctor or nurse.  This includes any 

possible side effects not listed in this leaflet.  See section 4. 
 
What is in this leaflet 
1. What Zolgensma is and what it is used for 
2. What you need to know before your child is given Zolgensma 
3. How Zolgensma is given 
4. Possible side effects 
5. How to store Zolgensma 
6. Contents of the pack and other information 
 
 
1. What Zolgensma is and what it is used for 
 
What Zolgensma is 
Zolgensma is a type of medicine called a ‘gene therapy’.  It contains the active ingredient 
onasemnogene abeparvovec which contains human genetic material. 
 
What Zolgensma is used for 
Zolgensma is used to treat babies and young children who have a rare, serious inherited condition 
called ‘spinal muscular atrophy’ (SMA).   
 
How Zolgensma works 
SMA occurs when there is a missing or abnormal version of a gene needed to make an essential 
protein called ‘Survival Motor Neuron’ (SMN) protein.  Lack of SMN protein causes nerves that 
control muscles (motor neurons) to die. This results in muscles becoming weak and wasting away, 
with eventual loss of movement.  
 
Zolgensma works by supplying a fully functioning copy of the SMN gene which then helps the body 
produce enough SMN protein. The gene is delivered into the cells where it is needed using a modified 
virus that does not cause disease in humans.  
 
 
2. What you need to know before your child is given Zolgensma 
 
Do NOT use Zolgensma 
Your child must NOT be given Zolgensma if they are allergic to onasemnogene abeparvovec or any 
of the other ingredients of this medicine (listed in section 6). 
 



34 

Warnings and precautions 
 
Your child’s doctor will carry out tests for antibodies before treatment to help decide if this medicine 
is suitable for your child.   
 
Liver problems 
Talk to your child’s doctor or nurse before your child is given this medicine if your child has had any 
problems with his/her liver. Zolgensma can cause an immune response that could lead to an increase 
in enzymes produced by the liver.   
 
Your child will have a blood test to check liver function before starting treatment with Zolgensma. 
They will also have regular blood tests for at least 3 months after treatment to monitor for increases in 
liver enzymes.   
 
Respiratory infection 
If your child develops a viral respiratory infection (e.g. cold, flu or bronchiolitis) before or after being 
treated with Zolgensma this could possibly lead to other more serious complications. Signs of a 
possible viral respiratory infection you need to look out for in your child include coughing, wheezing, 
sneezing, runny nose, sore throat or fever. Tell your child’s doctor straightaway if you notice your 
child develops any of these symptoms.   
 
Regular blood tests 
Zolgensma can lower blood-platelet count (thrombocytopenia).  Possible signs of a low blood-platelet 
count you need to look out for after your child is given Zolgensma include abnormal bruising or 
bleeding (see section 4 for more information).   
 
Zolgensma may cause raised levels of a heart/cardiac specific protein called ‘troponin-I’ that may 
indicate injury to the heart. Possible signs you need to look out for after your child is given Zolgensma 
include pale grey/blue skin colour, difficulty in breathing, swelling of the limbs or abdomen (see 
section 4 for more information).   
 
Your child will have a blood test to check blood-platelet count and troponin-I level before starting 
treatment with Zolgensma. Your child will also have regular blood tests for a period of time after 
treatment to monitor for changes in blood-platelets and troponin-I levels. 
 
Other medicines and Zolgensma 
Tell your child’s doctor or nurse if your child is taking, has recently taken or might take any other 
medicines. 
 
Prednisolone 
Your child will also be given a medicine called ‘prednisolone’ for a period of time (see also section 3) 
as part of their treatment with Zolgensma.  This is a type of medicine called a ‘corticosteroid’ which 
will help manage any potential increase in liver enzymes that your child could develop after being 
given Zolgensma. Your child’s doctor will decide if your child should be given prednisolone or 
another corticosteroid.  
 
Vaccinations 
As corticosteroids can affect the body’s immune system, your child’s doctor may decide to delay 
giving some vaccinations to your child while he/she is receiving prednisolone/corticosteroid 
treatment.  Talk to your child’s doctor or nurse if you have any questions. 
 
Zolgensma contains sodium 
This medicine contains 4.6 mg sodium per mL, equivalent to 0.23% of the WHO recommended 
maximum daily intake of 2 g sodium for an adult. Each 5.5 Ml vial contains 25.3 mg sodium, and each 
8.3 mL vial contains 38.2 mg sodium.  
 



35 

Additional information for parents/caregiver 
 
Advanced SMA 
Zolgensma can rescue viable motor neurons, but does not rescue dead motor neurons. Children with 
less severe symptoms of SMA (such as absent reflexes or reduced muscle tone) may have sufficient 
live motor neurons so as to receive significant benefit from Zolgensma treatment. Zolgensma may not 
work as well in children with severe muscle weakness or paralysis, breathing problems or who are not 
able to swallow, or in children who have significant malformation (such as heart defects), including 
patients with SMA Type 0, as these symptoms imply limited potential improvement after treatment 
with Zolgensma. Your child’s doctor will decide if your child should be given this medicine. 
 
Hygiene care 
The active substance in Zolgensma may temporarily be excreted through your child’s bodily waste.  
Parents and caregivers should follow good hand-hygiene for up to 1 month after your child is given 
Zolgensma. Wear protective gloves when coming into direct contact with your child’s bodily fluids or 
waste and wash hands thoroughly afterwards with soap and warm running water, or an alcohol-based 
hand sanitiser. Double bags should be used to dispose of soiled nappies and other waste.  Disposable 
nappies may still be disposed of in household waste. 
 
You should continue to follow these instructions for at least 1 month after your child’s treatment with 
Zolgensma.  Talk to your child’s doctor or nurse if you have any questions. 
 
 
3. How Zolgensma is given 
 
Zolgensma will be given to your child by a doctor or nurse trained in the management of your child’s 
condition. 
 
The amount of Zolgensma your child will receive will be worked out by your child’s doctor depending 
on the child’s weight. The dose is measured in units called vector genomes. 
 
The recommended dose is 1.1 x 1014 vector genomes per kg of body weight.  This will be given 
intravenously (into a vein) to your child by a single infusion (drip) over a period of approximately 
1 hour.  
 
Zolgensma will be given to your child ONCE only. 
 
Your child will also be given treatment with prednisolone (or another corticosteroid) by mouth, 
starting 24 hours before being given Zolgensma.  The dose of corticosteroid will also depend on your 
child’s weight. The recommended dose of prednisolone is 1 mg per kg body weight daily. Your child’s 
doctor will work out the total dose to give. 
 
Your child will be given corticosteroid treatment daily for approximately 2 months after the dose of 
Zolgensma, or until your child’s increased liver enzymes decrease to an acceptable level.  The dose of 
corticosteroid given to your child will be slowly reduced until treatment can be fully stopped.  Your 
child’s doctor will explain when and how they will stop this treatment for your child. 
 
If you have any further questions on the use of Zolgensma or prednisolone ask your child’s doctor or 
nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Seek urgent medical attention if your child develops any of the following serious side effects (these 
occur commonly, i.e. may affect up to 1 in 10 people): 



36 

• bruising or bleeding for longer than usual if your child has been hurt - these may be signs of a 
low blood-platelet count. 

• pale grey or blue skin colour, difficulty in breathing (e.g. rapid breathing, shortness of breath), 
swelling of the limbs or abdomen - these may be signs of possible problems with the heart. 

 
Talk to your child’s doctor or nurse if your child develops any other side effects.  These can include: 
 
Very common (may affect more than 1 in 10 people) 
• increases in liver enzymes (transaminases) seen in blood tests. 
 
Common (may affect up to 1 in 10 people): 
• increases in liver enzymes (aspartate aminotransferase, alanine aminotransferase) seen in blood 

tests; 
• vomiting;  
• fever. 
 
Reporting of side effects 
If your child gets any side effects, talk to your child’s doctor or nurse.  This includes any possible side 
effects not listed in this leaflet.  You can also report side effects directly via the national reporting 
system listed in Appendix V.  By reporting side effects, you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Zolgensma 
 
Do not use this medicine after the expiry date which is stated on the vial label and carton after EXP.  
The expiry date refers to the last day of that month. 
 
Vials will be transported frozen (at or below -60ºC). 
 
Upon receipt vials should be refrigerated at 2°C to 8°C immediately, and in the original carton.  
Zolgensma therapy should be initiated within 14 days of receipt of vials. 
 
 
6. Contents of the pack and other information 
 
What Zolgensma contains 
- The active substance is onasemnogene abeparvovec. Each vial contains onasemnogene 

abeparvovec with a nominal concentration of 2 × 1013 vg/mL.   
- The other ingredients are tromethamine, magnesium chloride, sodium chloride, poloxamer 188, 

hydrochloric acid (for pH adjustment) and water for injections. 
 
What Zolgensma looks like and contents of the pack 
Zolgensma is a clear to slightly opaque, colourless to faint white solution for infusion. 
 
Zolgensma may be supplied in vials containing a nominal fill volume of either of 5.5 mL or 8.3 mL.  
Each vial is for single use only. 
 
Each carton will contain between 2 to 14 vials. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


37 

Marketing Authorisation Holder 
AveXis EU Limited 
Block B, The Crescent Building 
Northwood, Santry 
Dublin 9 
D09 C6X8 
Ireland 
Tel: +351 30 88 00 322 
 
Manufacturer 
Almac Pharma Services Limited 
Finnabair Industrial Estate 
Dundalk, Co. Louth 
A91 P9KD 
Ireland 
 
For any information about this medicine, please contact the Marketing Authorisation Holder. 
 
This leaflet was last revised in 
 
This medicine has been given ‘conditional approval’. This means that there is more evidence to come 
about this medicine. The European Medicines Agency will review new information on this medicine 
at least every year and this leaflet will be updated as necessary. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  There are also links to other websites about rare diseases and treatments. 
 
-------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Important: Please refer to the Summary of Product Characteristics (SmPC) before using. 
 
Each vial is for single use only. 
 
This medicinal product contains genetically-modified organisms.  Local guidelines on handling of 
biological waste should be followed. 
 
Handling  
• Zolgensma should be handled aseptically under sterile conditions.   
• Personal protective equipment (including gloves, safety goggles, laboratory coat and sleeves) 

should be worn while handling or administering Zolgensma. Personnel should not work with 
Zolgensma if skin is cut or scratched. 

• All spills of Zolgensma must be wiped with absorbent gauze pads and the spill area must be 
disinfected using a bleach solution followed by alcohol wipes. All clean-up materials must be 
double bagged and disposed of in accordance with local guidelines on handling of biological 
waste. 

• All materials that may have come in contact with Zolgensma (e.g. vial, all materials used for 
injection, including sterile drapes and needles) must be disposed of in accordance with local 
guidelines on handling of biological waste. 

 
Accidental exposure  
Accidental exposure to Zolgensma must be avoided.  
 



38 

In case of accidental exposure to skin, the affected area must be thoroughly cleansed with soap and 
water for at least 15 minutes. In case of accidental exposure to eyes, the affected area must be 
thoroughly flushed with water for at least 15 minutes. 
 
Storage 
Vials will be transported frozen (at or below -60ºC).  Upon receipt vials should be refrigerated at 
2°C to 8°C immediately, and in the original carton.  Zolgensma therapy should be initiated within 
14 days of receipt of vials. The date of receipt should be marked on the original carton before the 
product is stored in the refrigerator. 
 
Preparation 
Vials should be thawed before use:   
• For packs containing up to 9 vials – thaw for approximately 12 hours in the refrigerator (2ºC to 

8ºC) or 4 hours at room temperature (20°C to 25°C).  
• For packs containing up to 14 vials – thaw for approximately 16 hours in the refrigerator (2ºC to 

8ºC) or 6 hours at room temperature (20°C to 25°C). 
 
Do not use Zolgensma unless thawed. 
 
Once thawed, the medicinal product should not be re-frozen. 
 
After thawing, gently swirl Zolgensma.  Do NOT shake. 
 
Do not use this medicine if you notice any particles or discolouration once the frozen product has 
thawed and prior to administration. 
 
After thawing, Zolgensma should be given as soon as possible.   
 
Administration 
Zolgensma should be given to patients ONCE only. 
 
The dose of Zolgensma and exact number of vials required for each patient is calculated according to 
the patient’s weight (see SmPC sections 4.2 and 6.5). 
 
To administer Zolgensma, draw the entire dose volume into the syringe.  Once the dose volume is 
drawn into the syringe it must be administered within 8 hours. Remove any air in the syringe and 
prepare the infusion bag before administering to the patient via intravenous infusion through a venous 
catheter.  Insertion of a secondary (‘back-up’) catheter is recommended in case of blockage in the 
primary catheter. 
 
Zolgensma should be administered with the syringe pump as a single intravenous infusion with a slow 
infusion of approximately 60 minutes.  It should be administered as an intravenous infusion only.  It 
should not be administered as a rapid intravenous injection or bolus. Following completion of 
infusion, the line should be flushed with saline. 
 
Disposal 
Any unused medicinal product or waste material should be disposed of in accordance with local 
guidelines on handling of biological waste. 
 
Temporary Zolgensma shedding may occur, primarily through bodily waste.  Caregivers and patient 
families should be advised on the following instructions for the proper handling of patient bodily 
fluids and waste: 
• Good hand-hygiene (wearing protective gloves and washing hands thoroughly afterwards with 

soap and warm running water, or an alcohol-based hand sanitiser) is required when coming into 
direct contact with patient bodily fluids and waste for a minimum of 1 month after Zolgensma 
treatment.   



39 

• Disposable diapers should be sealed in double plastics bags and can be disposed of in household 
waste. 

  



40 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Annex IV 

Conclusions on the granting of the conditional marketing authorisation presented by the 
European Medicines Agency 



41 

Conclusions presented by the European Medicines Agency on: 

• Conditional marketing authorisation 
 
The CHMP having considered the application is of the opinion that the risk-benefit balance is 
favourable to recommend the granting of the conditional marketing authorisation as further explained 
in the European Public Assessment Report. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE CONDITIONAL MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET