Spinraza

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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 
 
Spinraza 12 mg solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each 5 ml vial contains nusinersen sodium equivalent to 12 mg nusinersen. 
Each ml contains 2.4 mg of nusinersen. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection. 
 
Clear and colourless solution with pH of approximately 7.2. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Spinraza is indicated for the treatment of 5q Spinal Muscular Atrophy. 
 
4.2 Posology and method of administration 
 
Treatment with Spinraza should only be initiated by a physician with experience in the management of 
spinal muscular atrophy (SMA). 
 
The decision to treat should be based on an individualised expert evaluation of the expected benefits of 
treatment for that individual, balanced against the potential risk of treatment with Spinraza. Patients 
with profound hypotonia and respiratory failure at birth, where Spinraza has not been studied, may not 
experience a clinically meaningful benefit due to severe SMN protein deficiency. 
 
Posology 
 
Spinraza is for intrathecal use by lumbar puncture. 
 
The recommended dosage is 12 mg (5 ml) per administration. 
Spinraza treatment should be initiated as early as possible after diagnosis with 4 loading doses on 
Days 0, 14, 28 and 63. A maintenance dose should be administered once every 4 months thereafter. 
 
Duration of treatment 
Information on long term efficacy of this medicinal product is not available. The need for continuation 
of therapy should be reviewed regularly and considered on an individual basis depending on the 
patient’s clinical presentation and response to the therapy. 
 
Missed or delayed doses 
If a loading dose is delayed or missed Spinraza should be administered as soon as possible, with at 
least 14 days between doses, and continue dosing at the prescribed frequency. If a maintenance dose is 



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delayed or missed, Spinraza should be administered as soon as possible and dosing continued every 4 
months. 
 
Special populations 
 
Renal impairment 
Spinraza has not been studied in patients with renal impairment. The safety and efficacy in patients 
with renal impairment has not been established and they should be closely observed. 
 
Hepatic impairment 
Spinraza has not been studied in patients with hepatic impairment. Spinraza is not metabolised via the 
cytochrome P450 enzyme system in the liver, therefore dose adjustment is unlikely to be required in 
patients with hepatic impairment (see sections 4.5 and 5.2). 
 
Method of administration 
 
Treatment should be administered by health care professionals experienced in performing lumbar 
punctures. 
 
Spinraza is administered as an intrathecal bolus injection over 1 to 3 minutes, using a spinal 
anaesthesia needle. The injection must not be administered in areas of the skin where there are signs of 
infection or inflammation. It is recommended that the volume of cerebral spinal fluid (CSF), 
equivalent to the volume of Spinraza to be injected, is removed prior to administration of Spinraza. 
 
Sedation may be required to administer Spinraza, as indicated by the clinical condition of the patient. 
Ultrasound (or other imaging techniques) may be considered to guide intrathecal administration of 
Spinraza, particularly in younger patients and in patients with scoliosis. Aseptic technique should be 
used when preparing and administering Spinraza; see instructions for use in section 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 
 
Lumbar puncture procedure 
 
There is a risk of adverse reactions occurring as part of the lumbar puncture procedure (e.g. headache, 
back pain, vomiting; see section 4.8). Potential difficulties with this route of administration may be 
seen in very young patients and those with scoliosis. The use of ultrasound or other imaging 
techniques to assist with intrathecal administration of Spinraza, can be considered at the physician’s 
discretion. 
 
Thrombocytopenia and coagulation abnormalities 
 
Thrombocytopenia and coagulation abnormalities, including acute severe thrombocytopenia, have 
been observed after administration of other subcutaneously or intravenously administered antisense 
oligonucleotides. If clinically indicated, platelet and coagulation laboratory testing is recommended 
prior to administration of Spinraza. 
 
Renal toxicity 
 
Renal toxicity has been observed after administration of other subcutaneously and intravenously 
administered antisense oligonucleotides. If clinically indicated, urine protein testing (preferably using 
a first morning urine specimen) is recommended. For persistent elevated urinary protein, further 
evaluation should be considered. 
 



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Hydrocephalus 
 
There have been reports of communicating hydrocephalus not related to meningitis or bleeding in 
patients treated with nusinersen in the post-marketing setting. Some patients were implanted with a 
ventriculo-peritoneal shunt. In patients with decreased consciousness, an evaluation for hydrocephalus 
should be considered. The benefits-and risks of nusinersen treatment in patients with a ventriculo-
peritoneal shunt are unknown at present and the maintenance of treatment needs to be carefully 
considered. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. In vitro studies indicated that nusinersen is not an inducer 
or inhibitor of CYP450 mediated metabolism. In vitro studies indicate that the likelihood for 
interactions with nusinersen due to competition for plasma protein binding, or competition with or 
inhibition of transporters is low. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of nusinersen in pregnant women. Animal studies 
do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). 
As a precautionary measure, it is preferable to avoid the use of Spinraza during pregnancy. 
 
Breast-feeding 
 
It is unknown whether nusinersen/metabolites are excreted in human milk. 
 
A risk to the newborn/infants cannot be excluded. A decision must be made whether to discontinue 
breast-feeding or to discontinue/abstain from Spinraza therapy taking into account the benefit of 
breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
In toxicity studies in animals no effects on male or female fertility were observed (see section 5.3). 
There are no data available on the potential effects on fertility in humans. 
 
4.7 Effects on ability to drive and use machines 
 
Spinraza has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of safety profile 
 
The safety assessment of Spinraza was based on two Phase 3 clinical studies in infants (CS3B) and 
children (CS4) with SMA, together with one Phase 2 study in infants and children with SMA (CS7) 
and open-label studies including pre-symptomatic infants (CS5) genetically diagnosed with SMA and 
infants and children with SMA. Study CS11 enrolled infantile and later-onset patients including those 
who had completed studies CS3B, CS4 and CS12. Of the 346 patients who received Spinraza up to a 
maximum of 5 years, 258 patients received treatment for at least 1 year. 
 
Tabulated list of adverse reactions 
 
The assessment of undesirable effects is based on the following frequency data: 
Very common ( ≥ 1/10) 
Not known (cannot be estimated from the available data) 



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Table 1: Adverse reactions related to lumbar puncture procedure reported in CS4 (later onset SMA) 
with an incidence at least 5% higher in patients treated with Spinraza than sham-control 
 
MedDRA System Organ Class MedDRA preferred term Spinraza frequency category, n=84 

Nervous system disorders Headache* Very common 
Gastrointestinal disorders Vomiting*  Very common 
Musculoskeletal and connective 
tissue disorders 

Back pain* Very common 

*Adverse events considered related to the lumbar puncture procedure. These events can be considered manifestations of 
post-lumbar puncture syndrome. 
 

 

Post-marketing experience 

Adverse reactions have been identified during post-approval use of Spinraza. Among patients treated 
with Spinraza by lumbar puncture, serious infection, such as meningitis, has been observed. 
Communicating hydrocephalus, aseptic meningitis and hypersensitivity (e.g. angioedema, urticaria 
and rash) have also been reported. The frequency of these reactions is not known as they have been 
reported from the post marketing setting. 
 

Description of selected adverse reactions 
 

Adverse reactions associated with the administration of Spinraza by lumbar puncture have been 
observed. The majority of these are reported within 72 hours of the procedure. The incidence and 
severity of these events were consistent with events expected to occur with lumbar puncture. No 
serious complications of lumbar puncture, such as serious infections, have been observed in the 
clinical trials of Spinraza. 
 
Some adverse events commonly associated with lumbar puncture (e.g. headache and back pain) could 
not be assessed in the infant population exposed to Spinraza due to the limited communication 
appropriate for that age group. 
 
Immunogenicity 
 
The immunogenic response to nusinersen was determined in 346 patients with baseline and 
post-baseline plasma samples evaluated for anti-drug antibodies (ADA). Overall, the incidence of 
ADAs was low, with 15 (4%) patients classified as ADA positive overall, of which 4 had a transient 
response, 5 had a persistent response, and 6 patients had responses which could not be classified as 
transient or persistent at the time of data cut off. The impact of immunogenicity on safety was not 
formally analysed as the number of patients with ADAs was low. However, individual safety data for 
the treatment-emergent ADA-positive cases were reviewed, and no AEs of interest were identified. 
 
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 cases of overdose associated with adverse reactions were reported in clinical studies. 
 
In the event of an overdose, supportive medical care should be provided including consulting with a 
healthcare professional and close observation of the clinical status of the patient. 

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


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5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other drugs for disorders of the musculo-skeletal system, ATC code: 
M09AX07 
 
Mechanism of action 
 
Nusinersen is an antisense oligonucleotide (ASO) which increases the proportion of exon 7 inclusion 
in survival motor neuron 2 (SMN2) messenger ribonucleic acid (mRNA) transcripts by binding to an 
intronic splice silencing site (ISS-N1) found in intron 7 of the SMN2 pre-messenger ribonucleic 
acid (pre-mRNA). By binding, the ASO displaces splicing factors, which normally suppress splicing. 
Displacement of these factors leads to retention of exon 7 in the SMN2 mRNA and hence when SMN2 
mRNA is produced, it can be translated into the functional full length SMN protein. 
 
SMA is a progressive neuromuscular disease resulting from mutations in chromosome 5q in the SMN1 
gene. A second gene SMN2, located near SMN1, is responsible for a small amount of SMN protein 
production. SMA is a clinical spectrum of disease with disease severity linked to fewer numbers of 
SMN2 gene copies and younger age of symptom onset. 
 
Clinical efficacy and safety 
 
Symptomatic patients 
 
Infantile onset 
Study CS3B (ENDEAR) was a Phase 3, randomized, double-blind, sham-procedure controlled study 
conducted in 121 symptomatic infants ≤ 7 months of age, diagnosed with SMA (symptom onset before 
6 months of age). CS3B was designed to assess the effect of Spinraza on motor function and survival. 
Patients were randomized 2:1 to either Spinraza (as per the approved dosing regimen) or sham-control, 
with a length of treatment ranging from 6 to 442 days. 
 
The median age of onset of clinical signs and symptoms of SMA was 6.5 weeks and 8 weeks for 
Spinraza treated versus sham-control patients respectively, with 99% of patients having 2 copies of the 
SMN2 gene and therefore deemed most likely to develop Type I SMA. The median age when patients 
received their first dose was 164.5 days for treated patients, and 205 days for sham-control. Baseline 
disease characteristics were largely similar in the Spinraza treated patients and sham-control patients 
except that Spinraza treated patients at baseline had a higher percentage compared to sham-control 
patients of paradoxical breathing (89% vs 66%), pneumonia or respiratory symptoms (35% vs 22%), 
swallowing or feeding difficulties (51% vs 29%) and requirement for respiratory support 
(26% vs 15%). 
 
At the final analysis, a statistically significant greater percentage of patients achieved the definition of 
a motor milestone responder in the Spinraza group (51%) compared to the sham-control 
group (0%) (p<0.0001). Time to death or permanent ventilation (≥ 16 hours ventilation/day 
continuously for > 21 days in the absence of an acute reversible event or tracheostomy) was assessed 
as the primary endpoint. Statistically significant effects on event-free survival, overall survival, the 
proportion of patients achieving the definition of a motor milestone responder, and the percentage of 
patients with at least a 4-point improvement from baseline in Children’s Hospital of Philadelphia 
Infant Test for Neuromuscular Disease (CHOP INTEND) score were observed in patients in the 
Spinraza group compared to those in the sham-control group (Table 2). 
 



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In the efficacy set, 18 patients (25%) in the Spinraza group and 12 patients (32%) in the sham-control 
group required permanent ventilation. Of these patients, 6 (33%) in the Spinraza group and 0 (0%) in 
the sham-control group met the protocol-defined criteria for a motor-milestone responder. 
 
Table 2: Primary and secondary endpoints at final analysis – Study CS3B 

Efficacy Parameter Spinraza treated Patients Sham-control Patients 
 

Survival 
Event-free survival2 
Number of patients who died or 
received permanent ventilation 
Hazard ratio (95% CI) 
p-value6 

 
31 (39%) 

 

 
28 (68%)  

0.53 (0.32 -0.89) 
p = 0.0046 

Overall survival2 
Number of patients who died 
Hazard Ratio (95% CI) 
p-value6 

 
13 (16%) 

 
16 (39%) 

0.37 (0.18 – 0.77) 
p=0.0041 

Motor function 
Motor milestones3 
Proportion achieving pre-defined 
motor milestone responder criteria 
(HINE section 2)4,5 

Proportion at Day 183 
Proportion at Day 302 
Proportion at Day 394 

Proportion with improvement in total 
motor milestone score 
Proportion with worsening in total 
motor milestone score 

 
37 (51%)1 
p<0.0001 

 
41% 
45% 
54% 

49 (67%) 
 

1 (1%) 

 
0 (0%) 

 
 

5% 
0% 
0% 

5 (14%) 
 

8 (22%) 

CHOP INTEND3 
Proportion achieving a 4-point 
improvement 
Proportion achieving a 4-point 
worsening 
Proportion with any improvement 
Proportion with any worsening  

 
52 (71%) 
p<0.0001 

2 (3%) 
 

53 (73%) 
5 (7%) 

 
1 (3%) 

 
17 (46%) 

 
1 (3%) 

18 (49%) 
1CS3B was stopped following positive statistical analysis on the primary endpoint at interim analysis (statistically 
significantly greater percentage of patients achieved the definition of a motor milestone responder in the Spinraza 
group (41%) compared to the sham-control group (0%), p<0.0001) 
2At the final analysis, event-free survival and overall survival were assessed using the Intent to Treat population (ITT 
Spinraza n=80; Sham-control n=41). 
3At the final analysis, CHOP INTEND and motor milestone analyses were conducted using the Efficacy Set (Spinraza n=73; 
Sham-control n=37). 
4Assessed at the later of Day 183, Day 302, and Day 394 Study Visit 
5According to Hammersmith Infant Neurological Examination (HINE) section 2: ≥2 point increase [or maximal score] in 
ability to kick, OR ≥1 point increase in the motor milestones of head control, rolling, sitting, crawling, standing or walking, 
AND improvement in more categories of motor milestones than worsening, defined as a responder for this primary analysis. 
6Based on log-rank test stratified by disease duration 
 
The extent of improvement in CHOP INTEND is shown in Figure 1 (change from baseline score for 
each subject). 
 



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Figure 1: Change in CHOP INTEND from Baseline to Later of Day 183, Day 302, and Day 394 Study 
Visit – Endear Study /CS3B (Efficacy Set, ES) 

 
 
To allow for long term follow up of these patients, at the end of Study CS3B, 89 patients 
(Spinraza: n=65; sham-control: n=24) enrolled in Study CS11 (SHINE). Study CS11 is an open label 
extension study for SMA patients who previously participated in the other Spinraza clinical studies. In 
Study CS11 all patients received Spinraza, with the length of treatment ranging from 65 to 592 days 
(median 289 days) at the time of interim analysis. Improvements in motor function were observed 
among patients continuing Spinraza from Study CS3B, as well as those who initiated Spinraza in 
Study CS11 (Figure 3), with the greatest benefit observed in those with earlier treatment initiation. 
Among patients without permanent ventilation at the baseline of Study CS11, a majority were alive 
and without permanent ventilation at the time of interim analysis. 
 
In patients randomized to Spinraza in Study CS3B and including the experience in Study CS11, the 
median time to death or permanent ventilation was 73 weeks. At the time of a Study CS11 interim 
analysis, 61 out of 65 patients (94%) were alive. Of the 45 patients who had not met the definition of 
permanent ventilation in Study CS3B, 38 patients (84%) were alive without permanent ventilation in 
Study CS11 at the time of interim analysis. Further improvement in mean total motor milestone 
(HINE-Section 2) (2.1; SD 4.36; n=22) and CHOP INTEND (4.68; SD 3.993, n=22) scores were 
observed from baseline to Study Day 304 in Study CS11. 
 
Patients who first initiated Spinraza treatment in Study CS11 (n=24; sham control in Study CS3B) 
were of a median age of 17.8 months (range 10 - 23 months) and had a mean CHOP INTEND score of 
17.25 (range 2.0 - 46.0) at baseline in Study CS11. At the time of interim analysis, 22 out of 24 
patients (92%) were alive. Of the twelve patients (50%) who had not met the definition of permanent 
ventilation in Study CS3B, 7 patients (58%) were alive without permanent ventilation in Study CS11. 
The median time to death or permanent ventilation was 50.9 weeks after initiation of Spinraza 
treatment in Study CS11. Improvement in mean total motor milestone (HINE-Section 2) (1.2; SD 1.8; 
n=12) and CHOP INTEND (3.58; SD 7.051, n=12) scores were observed from baseline to Study Day 
304 in Study CS11. 
 
These results are supported by an open-label Phase 2 study in symptomatic patients diagnosed with 
SMA (CS3A). Median age of onset of clinical signs and symptoms was 56 days and patients had either 
2 SMN2 gene copies (n=17) or 3 SMN2 gene copies (n=2) (SMN2 gene copy number unknown for 
1 patient). Patients in this study were deemed most likely to develop Type I SMA. The median age at 
first dose was 162 days. 



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The primary endpoint was the proportion of patients who improved in one or more categories in motor 
milestones (according to HINE section 2: ≥2 point increase [or maximal score] in ability to kick or 
voluntary grasp OR ≥1 point increase in the motor milestones of head control, rolling, sitting, 
crawling, standing or walking). Twelve out of 20 patients (60%) in the study met the primary endpoint 
with improvement in mean motor milestone achievement over time. An improvement in mean CHOP 
INTEND score over time was observed from baseline to day 1072 (mean change 21.30). Overall, 11 
out of 20 patients (55%) met the endpoint of an increase in total CHOP INTEND score of ≥4 points as 
of the last study visit. Of the 20 subjects enrolled, 11 (55%) were alive and free of permanent 
ventilation at the last visit. Four patients met the criteria for permanent ventilation and five patients 
died during the study. 
 
Later onset 
Study CS4 (CHERISH) was a Phase 3, randomised, double-blind, sham-procedure controlled study 
conducted in 126 symptomatic patients with later-onset SMA (symptom onset after 6 months of age). 
Patients were randomized 2:1 to either Spinraza (dosed with 3 loading doses and maintenance doses 
every 6 months) or sham-control, with a length of treatment ranging from 324 to 482 days. The 
median age at screening was 3 years, and the median age of onset of clinical signs and symptoms of 
SMA was 11 months. The majority of patients (88%) have 3 copies of the SMN2 gene (8% have 
2 copies, 2% have 4 copies, and 2% have an unknown copy number). At baseline, patients had a mean 
Hammersmith Functional Motor Scale Expanded (HFMSE) score of 21.6, a mean revised upper limb 
module (RULM) of 19.1, all had achieved independent sitting, and no patients had achieved 
independent walking. Patients in this study were deemed most likely to develop Type II or III SMA. 
Baseline disease characteristics were generally similar with the exception of an imbalance in the 
proportion of patients who had ever achieved the ability to stand without support (13% of patients in 
the Spinraza group and 29% in sham-control) or walk with support (24% of patients in the Spinraza 
group and 33% in sham-control). 
 
At the final analysis, a statistically significant improvement in HFMSE score from baseline to 
Month 15 was seen in the Spinraza group compared to the sham-control group (Table 3, Figure 2). 
The analysis was conducted in the ITT population (Spinraza: n=84; sham-control: n=42), and 
post-baseline HFMSE data for patients without a Month 15 visit were imputed using the multiple 
imputation method. An analysis of the subset of patients in the ITT population who had observed 
values at Month 15 demonstrated consistent, statistically significant results. Of those with observed 
values at Month 15, a higher proportion of Spinraza treated subjects had improvement (73% vs 41%, 
respectively) and a lower proportion of Spinraza treated subjects had worsening (23% vs 44%, 
respectively) in total HFMSE score compared to sham-control. Secondary endpoints including 
functional measures and WHO motor milestone achievement were formally statistically tested and are 
described in Table 3. 
 
Initiation of treatment sooner after symptom onset resulted in earlier and greater improvement in 
motor function than those with delayed treatment initiation; however, both groups experienced benefit 
compared to sham-control. 
 



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Table 3: Primary and secondary endpoints at final analysis – Study CS41 
 Spinraza treated Patients  Sham-control Patients 

 
HFMSE score 
Change from baseline in total 
HFMSE score at 15 months1,2,3 
 
Proportion of patients who achieved 
at least a 3 point improvement from 
baseline to month 152 

 
3.9 (95% CI: 3.0, 4.9) 

p=0.0000001 
 

56.8% (95% CI:45.6, 68.1) 
P=0.00065 

 
-1.0 (95% CI: -2.5, 0.5) 

 
 

26.3% (95% CI: 12.4,40.2) 

RULM 
Mean change from baseline to month 
15 in total RULM score2,3 

 
4.2(95% CI: 3.4, 5.0) 

p=0.00000016  

 
0.5 (95% CI: -0.6, 1.6) 

WHO motor milestones 
Proportion of patients who achieved 
new motor milestones at 15 months4 

 
19.7% (95% CI: 10.9, 

31.3) 
p=0.0811 

 
5.9% (95% CI: 0.7, 

19.7) 
 

1CS4 was stopped following positive statistical analysis on the primary endpoint at interim analysis (statistically significant 
improvement from baseline HFMSE score was observed in Spinraza treated patients compared to the sham-control patients 
(Spinraza vs. sham-control: 4.0 vs. -1.9; p=0.0000002)) 
2 Assessed using the Intent to Treat population (Spinraza n=84; Sham-control n=42); data for patients without a Month 15 
visit were imputed using the multiple imputation method 
3Least squares mean 
4 Assessed using the Month 15 Efficacy Set (Spinraza n=66; Sham control n=34); analyses are based on 
imputed data when there are missing data. 
5 Based on logistic regression with treatment effect and adjustment for each subject's age at screening and HFMSE score at 
baseline 
6Nominal p value 
 
Figure 2: Mean change from baseline in HFMSE score over time at final analysis (ITT) – 
Study CS4 1,2 
 

 
 
Upon completion of Study CS4 (CHERISH) 125 patients enrolled in Study CS11 (SHINE), where all 
patients received Spinraza. The length of treatment ranged from 74 to 474 days (median 250 days) at 
the time of the interim analysis. A majority of Spinraza treated patients experienced stabilization or 
improvement in motor function, with the greatest benefit observed in those with earlier treatment 
initiation. 



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Of patients who initiated Spinraza treatment in Study CS4 (n=39), stabilization or additional 
improvements in mean HFMSE (0.2; SD 3.06) and RULM (0.7; SD 2.69) scores were observed from 
baseline to Study Day 265 in Study CS11. 
 
Patients who initiated Spinraza treatment in Study CS11 (n=20) had a median age of 4.0 years (range 3 
- 8 years). Of these patients, stabilization or improvement in mean HFMSE (1.4; SD 4.02) and RULM 
(2.1; SD 2.56) scores were observed from baseline to Study Day 265 in Study CS11. 
 
These results are supported by 2 open label studies (study CS2 and study CS12). The analysis included 
28 patients who received their first dose in study CS2, and then transferred to the extension phase, 
study CS12. The studies enrolled patients who were between 2 to 15 years of age at first dose. Of the 
28 patients, 3 were at least 18 years of age at their last study visit. 1 out of 28 patients had 2 SMN2 
gene copies, 21 had 3 copies, and 6 had 4 copies. 
 
Patients were assessed over a 3 year treatment period. A sustained improvement was seen in patients 
with Type II SMA who experienced a mean improvement from baseline HFMSE score of 5.1 
(SD 4.05, n=11) at Day 253, and 9.1(SD 6.61, n=9) at Day 1050. The mean total score was 26.4 
(SD 11.91) at Day 253 and 31.3 (SD 13.02) at Day 1050, no plateau was observed. Patients with 
Type III SMA demonstrated a mean improvement from baseline HFMSE score of 1.3 (SD 1.87, n=16) 
at Day 253 and 1.2 (SD 4.64, n=11) at Day 1050. The mean total score was 49.8 (SD 12.46) at 
Day 253 and 52.6 (SD 12.78) at 1050 days. 
 
In patients with Type II SMA the Upper Limb Module test was conducted with mean improvement of 
1.9 (SD 2.68, n=11) at Day 253 and 3.5 (SD 3.32, n=9) at Day 1050. The mean total score was13.8 
(SD 3.09) at Day 253 and 15.7 (SD 1.92) at Day 1050. 
 
The 6MWT (six-minute walk test) was conducted for ambulatory patients only. In these patients, a 
mean improvement of 28.6 meters (SD 47.22, n=12) at Day 253 and 86.5 metres (SD 40.58, n=8) at 
Day 1050. The mean 6MWT distance was 278.5 meters (SD 206.46) at Day 253 and 333.6 metres 
(SD 176.47) at Day 1050. Two previously non-independent ambulatory patients (Type III) achieved 
independent walking, and one non-ambulatory patient (Type II) achieved independent walking. 
 
An additional clinical study, CS7 (EMBRACE) was opened for patients not eligible for participation 
in Study CS3B or Study CS4 due to screening age or SMN2 copy number. CS7 is a phase 2, 
randomized, double-blind, sham-procedure study in symptomatic patients diagnosed with infantile-
onset SMA (≤6 months) or later-onset SMA (>6 months) and 2 or 3 copies of SMN2 (Part 1), 
followed by a long-term open label extension phase (Part 2). In Part 1 of the study, patients were 
followed for a median of 302 days. 
 
All patients who received Spinraza were alive as of the early termination of Part 1, however, one 
patient in the control arm died at Study Day 289. In addition, no patients in the Spinraza or sham-
control group required the use of permanent ventilation. Of the 13 patients with infantile-onset SMA, 
7 of out 9 patients (78%; 95%CI: 45, 94) in the Spinraza group and 0 out of 4 patients (0%; 95%CI: 0, 
60) in the sham group met the criteria for motor milestone response (according to HINE section 2: ≥2 
point increase [or maximal score] in ability to kick OR ≥1 point increase in the motor milestones of 
head control, rolling, sitting, crawling, standing or walking and improvement in more categories of 
motor milestones than worsening). Of the 8 patients with later-onset SMA, 4 out of 5 patients (80%; 
95% CI: 38, 96) in the Spinraza group and 2 out of 3 (67%; 95% CI: 21, 94) in the sham-control group 
met this definition of response. 
 
Pre-symptomatic infants 
 
Study CS5 (NURTURE) is an open-label study in pre-symptomatic infants genetically diagnosed with 
SMA, who were enrolled at 6 weeks of age or younger. Patients in this study were deemed most likely 
to develop Type I or II SMA. Median age at first dose was 22 days. 
 



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An interim analysis was conducted when patients had been on study for median of 27.1 months (15.1 -
35.5 months) and were of a median age at last visit of 26.0 months (14.0 -34.3 months). At the interim 
analysis, all 25 patients (2 SMN2 gene copies, n=15; 3 SMN2 gene copies, n=10) were alive without 
permanent ventilation. The primary endpoint, time to death or respiratory intervention (defined as 
invasive or non-invasive ventilation for ≥6 hours/day continuously for ≥7 consecutive days OR 
tracheostomy), could not be estimated as there were too few events. Four patients (2 SMN2 copies) 
required respiratory intervention >6 hours/day continuously for ≥7 days, all of whom initiated 
ventilatory support during an acute reversible illness 
 
Patients achieved milestones unexpected in Type I or II SMA and more consistent with normal 
development. At the interim analysis, all 25 (100%) patients had achieved the WHO motor milestone 
of sitting without support, 22 (88%) patients were walking with assistance. Among patients older than 
the WHO defined window for expected age of achievement (95th percentile), 17 of 22 (77%) had 
achieved walking alone. The mean CHOP INTEND score at last assessment was 61.0 (46 - 64) 
amongst patients with 2 SMN2 copies and 62.6 (58 - 64) amongst those with 3 SMN2 copies. All 
patients had the ability to suck and swallow at last assessment, with 22 (88%) infants achieving a 
maximal score on the HINE Section 1. 
 
The proportion of patients developing clinically manifested SMA was assessed amongst patients who 
reached the Day 700 visit at the interim analysis (n=16). The protocol-defined criteria for clinically 
manifested SMA included age-adjusted weight below the fifth WHO percentile, a decrease of 2 or 
more major weight growth curve percentiles, the placement of a percutaneous gastric tube, and/or the 
inability to achieve expected age-appropriate WHO milestones (sitting without support, standing with 
assistance, hands-and-knees crawling, walking with assistance, standing alone and walking alone). At 
day 700, 7 out of 11 patients (64%) with 2 SMN2 gene copies and 0 out of 5 patients (0%) with 3 
SMN2 copies, met the protocol-defined criteria of clinically manifested SMA, however, these patients 
were gaining weight and achieving WHO milestones, inconsistent with Type I SMA. A comparison of 
motor milestone achievement among the patients with symptomatic infantile-onset SMA and 
pre-symptomatic SMA is shown in Figure 3. 
 



13 

Figure 3: Change in HINE Motor Milestones versus Study days for Study CS3B (treated and 
sham-control), CS3A, CS5 and CS11 
 

 
 
5.2 Pharmacokinetic properties 
 
Single- and multiple-dose pharmacokinetics (PK) of nusinersen, administered via intrathecal injection, 
were determined in paediatric patients diagnosed with SMA. 
 
Absorption 
 
Intrathecal injection of nusinersen into the CSF allows nusinersen to be fully available for distribution 
from the CSF to the target central nervous system (CNS) tissues. Mean CSF trough concentrations of 
nusinersen accumulated approximately 1.4- to 3-fold after multiple loading and maintenance doses, 
and reached a steady state within approximately 24 months. Following intrathecal administration 
trough plasma concentrations of nusinersen were relatively low compared to the trough CSF 
concentration. Median plasma Tmax values ranged from 1.7 to 6.0 hours. Mean plasma Cmax and AUC 
values increased approximately dose proportionally over the evaluated dose range. There is no 
accumulation in plasma exposure measures (Cmax and AUC) after multiple doses. 
 
Distribution 
 
Autopsy data from patients (n=3) show that nusinersen administered intrathecally is broadly 
distributed within the CNS achieving therapeutic levels in the target spinal cord tissues. Presence of 
nusinersen was also demonstrated in neurons and other cell types in the spinal cord and brain, and 
peripheral tissues such as skeletal muscle, liver, and kidney. 
 
Biotransformation 
 
Nusinersen is metabolized slowly and predominantly via exonuclease (3’- and 5’) -mediated 
hydrolysis and is not a substrate for, or inhibitor or inducer of CYP450 enzymes. 
 



14 

Elimination 
 
The mean terminal elimination half-life in CSF is estimated at 135 to 177 days. The primary route of 
elimination is expected via urinary excretion of nusinersen and its metabolites. 
 
Interactions 
 
In vitro studies indicated that nusinersen is not an inducer or inhibitor of CYP450-mediated oxidative 
metabolism and therefore should not interfere with other medicinal products for these metabolic 
pathways. Nusinersen is not a substrate or inhibitor of human BCRP, P-gp, OAT1, OAT3, OCT1, 
OCT2, OATP1B1, OATP1B3, or BSEP transporters. 
 
Characteristics in specific patient populations 
 
Renal and hepatic impairment 
The pharmacokinetics of nusinersen in patients with renal or hepatic impairment has not been studied. 
The effect of hepatic or renal insufficiency as covariates could not be thoroughly evaluated in the 
population PK model given the rarity of patients displaying clinically relevant liver or kidney 
insufficiencies. Population PK analyses revealed no apparent correlation between hepatic and renal 
clinical chemistry markers and inter-subject variability. 
 
Race 
The majority of patients studied were Caucasian. The population PK analysis suggests that race is 
unlikely to affect the PK of nusinersen. 
 
5.3 Preclinical safety data 
 
Carcinogenesis 
 
Long-term studies in animals to evaluate the carcinogenic potential of nusinersen have not been 
performed. 
 
Mutagenesis 
 
Nusinersen demonstrated no evidence of genotoxicity. 
 
Reproductive toxicity 
 
Reproductive toxicology studies were conducted using subcutaneous administration of nusinersen in 
mice and rabbits. No impact on male or female fertility, or embryo-foetal development, or 
pre/post-natal development was observed. 
 
Toxicology 
 
In repeat-dose toxicity studies (14-weeks and 53-weeks) of intrathecal administration to juvenile 
cynomolgus monkeys, nusinersen was well tolerated. The exception was an acute, transient deficit in 
lower spinal reflexes which occurred at the highest dose levels in each study (3 or 4 mg per dose; 
equivalent to 30 or 40 mg per intrathecal dose in patients). These effects were observed within several 
hours post-dose and generally resolved within 48 hours. 
 
In the 53-week intrathecal dosing study in cynomolgus monkeys no toxicity effects were seen at levels 
up to 14-fold the recommended annual clinical maintenance dose. 
 
 



15 

6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium dihydrogen phosphate dihydrate 
Disodium phosphate 
Sodium chloride 
Potassium chloride 
Calcium chloride dihydrate 
Magnesium chloride hexahydrate 
Sodium hydroxide (for pH adjustment) 
Hydrochloric acid (for pH adjustment) 
Water for injections 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 
If no refrigeration is available, Spinraza may be stored in its original carton, protected from light at or 
below 30°C for up to 14 days. 
 
Prior to administration, unopened vials of Spinraza can be removed from and returned to the 
refrigerator if necessary. If removed from the original carton, the total combined time out of 
refrigeration should not exceed 30 hours, at a temperature that does not exceed 25°C. 
 
6.5 Nature and contents of container 
 
5 ml in a Type I glass vial with bromobutyl rubber stopper and an aluminium over-seal and plastic 
cap. 
Pack size of one vial per carton. 
 
6.6 Special precautions for disposal and other handling 
 
For single use only. 
 
Instructions for preparation of the medicinal product before administration 
 
1. The Spinraza vial should be inspected for particles prior to administration. If particles are observed 
and/or the liquid in the vial is not clear and colourless, the vial must not be used. 
2. Aseptic technique should be used when preparing Spinraza solution for intrathecal administration. 
3. The vial should be taken out of the refrigerator and allowed to warm to room temperature (25°C) 
without using external heat sources, prior to administration. 
4. If the vial remains unopened and the solution is not used, it should be returned back to the 
refrigerator (see section 6.4). 
5. Just prior to administration, remove the plastic cap and insert the syringe needle into the vial 
through the centre of the over-seal to remove the appropriate volume. Spinraza must not be diluted. 
The use of external filters is not required. 
6. Once drawn into the syringe, if the solution is not used within 6 hours, it must be discarded. 



16 

7. Any unused product or waste material must be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1188/001 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 30 May 2017 
 
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. 
 
  



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) 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 

 



18 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Biogen (Denmark) Manufacturing ApS  
Biogen Allé 1 
DK - 3400 Hillerød 
Denmark 
 
 
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: 
 

Description Due date 
Post-authorisation efficacy study (PAES): In order to evaluate the long term 
efficacy and safety of nusinersen in symptomatic patients with spinal muscular 
atrophy, the MAH should conduct and submit the results of the Phase 3, open-
label extension study (SHINE, CS11) 

Submission 
of study 
results: Q2 
2024. 



19 

Post-authorisation efficacy study (PAES): In order to evaluate the long term 
efficacy and safety of nusinersen in pre-symptomatic patients with spinal 
muscular atrophy, the MAH should conduct and submit the results of the Phase 2, 
open-label study (NURTURE (SM201)) 

Submission 
of study 
results: April 
2026. 

 
  



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



22 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Spinraza 12 mg solution for injection 
nusinersen 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 5 ml vial contains nusinersen sodium equivalent to 12 mg nusinersen (2.4 mg/ml). 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium dihydrogen phosphate dihydrate, disodium phosphate, sodium chloride, potassium chloride, 
calcium chloride dihydrate, magnesium chloride hexahydrate, sodium hydroxide, hydrochloric acid, 
water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intrathecal use. 
For 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 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 



23 

Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1188/001 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



24 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Spinraza 12 mg solution for injection 
nusinersen 
Intrathecal use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml 
 
 
6. OTHER 
 
 
 
  



25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



26 

Package leaflet: Information for the user 
 

Spinraza 12 mg solution for injection 
 

nusinersen 
 

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

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

possible side effects not listed in this leaflet. See section 4. 
 

What is in this leaflet 
 
1. What Spinraza is and what it is used for 
2. What you need to know before you or your child are given Spinraza 
3. How Spinraza is given 
4. Possible side effects 
5. How to store Spinraza 
6. Contents of the pack and other information 
 
 
1. What Spinraza is and what it is used for 
 
Spinraza contains the active substance nusinersen which belongs to a group of medicines known as 
antisense oligonucleotides. Spinraza is used to treat a genetic disease called spinal muscular atrophy 
(SMA). 
 
Spinal muscular atrophy is caused by a shortage of a protein called survival motor neuron (SMN) in 
the body. This results in the loss of nerve cells in the spine, leading to weakness of the muscles in the 
shoulders, hips, thighs and upper back. It may also weaken the muscles used for breathing and 
swallowing. 
 
Spinraza works by helping the body to produce more of the SMN protein that people with SMA are 
lacking. This reduces the loss of nerve cells and so may improve muscle strength. 
 
 
2. What you need to know before you or your child are given Spinraza 
 
Spinraza must not be given 
• If you or your child are allergic to nusinersen or any of the other ingredients of this medicine 

(listed in section 6). 
 
If you are not sure, talk to your doctor or nurse before you or your child are given Spinraza. 
 
Warnings and precautions 
There is a risk of side effects occuring after Spinraza is given by a lumbar puncture procedure (see 
section 3). This can include headaches, vomiting and back pain. There may also be difficulties with 
giving a medicine by this method in very young patients and those with scoliosis (twisted and curved 
spine). 
 



27 

 
Other products that are in the same group of medicines as Spinraza have been shown to affect the cells 
in the blood which help clotting. Before you or your child are given Spinraza your doctor may decide 
to do a blood test to check that your or your child’s blood can clot properly. This may not be required 
every time you or your child are given Spinraza. 
 
Other products that are in the same group of medicines as Spinraza have been shown to affect the 
kidneys. Before you or your child are given Spinraza your doctor may decide to do a urine test to 
check that your or your child’s kidneys are working normally. This may not be required every time 
you or your child are given Spinraza. 
 
There have been a small number of reports of patients developing hydrocephalus (a build-up of too 
much fluid around the brain) after Spinraza is given. Some of these patients had needed to have a 
device called a ventriculo-peritoneal shunt implanted to treat the hydrocephalus. If you notice any 
symptoms of increase in head size, decreased consciousness, persistent nausea, vomiting or headache; 
or other symptoms that cause you concern, please inform your or your child’s doctor to seek necessary 
treatment. The benefits and risks of continuing Spinraza whilst having a "ventriculo-peritoneal shunt" 
in place are not known at present. 
 
Talk to your doctor before you or your child are given Spinraza. 
 
Other medicines and Spinraza 
Tell your doctor if you or your child are taking, have recently taken any, or might take any other 
medicines in future. 
 
Pregnancy and breast-feeding  
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before being given this medicine. It is preferable to avoid the use of Spinraza 
during pregnancy and breast-feeding. 
 
Driving and using machines 
Spinraza has no or negligible influence on the ability to drive and use machines. 
 
Spinraza contains a small amount of sodium 
Each dose of Spinraza contains less than 1 mmol (23 mg) sodium. It is essentially ‘sodium-free’ and 
can be used by people on a sodium-restricted diet. 
 
 
3. How Spinraza is given 
 
The usual dose of Spinraza is 12 mg. 
 
Spinraza is given; 
• On the first day of treatment, day 0 
• Then around day 14, day 28 and day 63 
• Then once every 4 months. 
 
Spinraza is given by injection into the lower back. This injection, called a lumbar puncture, is done by 
inserting a needle into the space around the spinal cord. This will be done by a doctor experienced in 
doing lumbar punctures. You or your child may also be given a medicine to make you relax or sleep 
during the procedure. 
 
How long to use Spinraza 
Your doctor will tell you how long you or your child need to receive Spinraza. Don’t stop treatment 
with Spinraza unless your doctor tells you to. 
 



28 

If you or your child misses an injection 
If you or your child miss a dose of Spinraza, speak with your doctor so that Spinraza can be given as 
soon as possible. 
 
If you have any questions about how Spinraza is given, ask your doctor. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Side effects related to the lumbar puncture may occur while Spinraza is being given or afterwards. The 
majority of these side effects are reported within 72 hours of the procedure. 
 

Very common (may affect more than 1 in 10 people) 
• Back pain 
• Headache 
• Vomiting 

 
Additional side effects not seen in clinical trials: 

Not known (frequency cannot be estimated from the available data) 
• Serious infection related to lumbar puncture (e.g. meningitis) 
• Hydrocephalus (a build-up of too much fluid around the brain) 
• Meningitis not caused by an infection (inflammation of the membrane around the spinal cord 

and brain, which may present as neck stiffness, headache, fever, nausea and vomiting) 
• Hypersensitivity (an allergic or allergic-like reaction that may include swelling of your face, 

lips or tongue, rash, or itching) 
 
Reporting of side effects 
If you or your child get any side effects, talk to your 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 Spinraza 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton after “EXP”. The expiry 
date refers to the last day of that month. 
 
Store in a refrigerator (2°C to 8°C). Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 
If no refrigeration is available, Spinraza may be stored in its original carton, protected from light at or 
below 30°C for up to 14 days. 
 
Unopened vials of Spinraza can be removed from and returned to the refrigerator if necessary. If 
removed from the original carton, the total time out of refrigeration should not exceed 30 hours, at a 
temperature that does not exceed 25°C. 
 
 

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


29 

6. Contents of the pack and other information 
 
What Spinraza contains 
- The active substance is nusinersen. 
- Each 5 ml vial contains nusinersen sodium equivalent to 12 mg nusinersen. 
- Each ml contains 2.4 mg of nusinersen. 
- The other ingredients are sodium dihydrogen phosphate dihydrate, disodium phosphate, sodium 

chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, 
sodium hydroxide, hydrochloric acid, water for injections. 

 
What Spinraza looks like and contents of the pack 
Spinraza is a clear colourless solution for injection. 
Each carton of Spinraza contains one vial. 
Each vial is for single use. 
 
Marketing Authorisation Holder 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
Manufacturer 
Biogen (Denmark) Manufacturing ApS 
Biogen Allé 1 
DK - 3400 Hillerød 
Denmark 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Biogen Belgium N.V./S.A. 
Tél/Tel: +32 2 219 12 18 
 

Lietuva 
Ewopharma AG Atstovybė 
Tel: +370 52 14 02 60 

България 
ТП ЕВОФАРМА 
Teл.: +359 2 962 12 00  

Luxembourg/Luxemburg 
Biogen Belgium N.V./S.A. 
Tél/Tel: +32 2 219 12 18 
 

Česká republika 
Biogen (Czech Republic) s.r.o. 
Tel: +420 255 706 200 
 

Magyarország 
Biogen Hungary Kft. 
Tel.: +36 (1) 899 9883 

Danmark 
Biogen (Denmark) A/S 
Tlf: +45 77 41 57 57 
 

Malta 
Pharma MT limited 
Tel: +356 213 37008/9 
 

Deutschland 
Biogen GmbH 
Tel: +49 (0) 89 99 6170 
 

Nederland 
Biogen Netherlands B.V. 
Tel: +31 20 542 2000 

Eesti 
Ewopharma AG Eesti filiaal 
Tel: + 372 6 68 30 56 
 

Norge 
Biogen Norway AS 
Tlf: +47 23 40 01 00 



30 

Ελλάδα 
Genesis Pharma SA 
Τηλ: +30 210 8771500 
 

Österreich 
Biogen Austria GmbH 
Tel: +43 1 484 46 13 
 

España 
Biogen Spain SL 
Tel: +34 91 310 7110 
 

Polska 
Biogen Poland Sp. z o.o. 
Tel.: +48 22 351 51 00  

France 
Biogen France SAS 
Tél: +33 (0)1 41 37 95 95 

Portugal 
Biogen Portugal 
Tel.: +351 21 318 8450 
 

Hrvatska 
Medis Adria d.o.o. 
Tel: +385 (0) 1 230 34 46 
 

România 
Ewopharma AG Representative Office 
Tel: + 40 377 881 045 

Ireland 
Biogen Idec (Ireland) Ltd. 
Tel: +353 (0)1 463 7799 
 

Slovenija 
Biogen Pharma d.o.o. 
Tel.: +386 1 511 02 90 
 

Ísland 
Icepharma hf 
Sími: +354 540 8000 
 

Slovenská republika 
Biogen Slovakia s.r.o. 
Tel.: +421 2 323 340 08 

Italia 
Biogen Italia s.r.l. 
Tel: +39 02 584 9901 
 

Suomi/Finland 
Biogen Finland Oy 
Puh/Tel: +358 207 401 200 
 

Κύπρος 
Genesis Pharma Cyprus Ltd 
Τηλ: +357 22 765740 
 

Sverige 
Biogen Sweden AB 
Tel: +46 8 594 113 60 
 

Latvija 
Ewopharma AG pārstāvniecība 
Tel: + 371 66 16 40 32 
 

United Kingdom 
Biogen Idec Limited 
Tel: +44 (0) 1628 50 1000 
 

 
This leaflet was last revised in 
 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 
<------------------------------------------------------------------------------------------------------------------------> 
 
The following information is intended for healthcare professionals only: 

1. The Spinraza vial should be inspected for particles prior to administration. If particles are observed 
and/or the liquid in the vial is not clear and colourless, the vial must not be used. 

2. Aseptic technique should be used when preparing Spinraza solution for intrathecal administration. 

3. The vial should be taken out of the refrigerator and allowed to warm to room temperature (25°C) 
without using external heat sources, prior to administration. 

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


31 

4. If the vial remains unopened and the solution is not used, it should be returned back to the refrigerator. 

5. Just prior to administration, remove the plastic cap and insert the syringe needle into the vial through 
the center of the over-seal to remove the appropriate volume. Spinraza must not be diluted. The use of 
external filters is not required. 

6. Spinraza is administered as an intrathecal bolus injection over 1 to 3 minutes, using a spinal 
anaesthesia needle. 

7. The injection must not be administered in areas of the skin where there are signs of infection or 
inflammation. 

8. It is recommended that the volume of CSF, equivalent to the volume of Spinraza to be injected, is 
removed prior to administration of Spinraza. 

9. Once drawn into the syringe, if the solution is not used within 6 hours, it must be discarded. 

10. Any unused product or waste material must be disposed of in accordance with local requirements. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) 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
	A. LABELLING
	B. PACKAGE LEAFLET