Soliris

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ANNEX I 

 
SUMMARY OF PRODUCT CHARACTERISTICS 

 
  



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1. NAME OF THE MEDICINAL PRODUCT 
 
Soliris 300 mg concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Eculizumab is a humanised monoclonal (IgG2/4κ) antibody produced in NS0 cell line by recombinant DNA 
technology. 
 
One vial of 30 ml contains 300 mg of eculizumab (10 mg/ml). 
 
After dilution, the final concentration of the solution to be infused is 5 mg/ml. 
 
Excipients with known effect: Sodium (5 mmol per vial) 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion. 
 
Clear, colorless, pH 7.0 solution.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indication 
 
Soliris is indicated in adults and children for the treatment of: 
- Paroxysmal nocturnal haemoglobinuria (PNH). 

Evidence of clinical benefit is demonstrated in patients with haemolysis with clinical symptom(s) 
indicative of high disease activity, regardless of transfusion history (see section 5.1). 

- Atypical haemolytic uremic syndrome (aHUS) (see section 5.1). 
 
Soliris is indicated in adults for the treatment of: 
- Refractory generalized myasthenia gravis (gMG) in patients who are anti-acetylcholine receptor 

(AChR) antibody-positive (see section 5.1). 
- Neuromyelitis optica spectrum disorder (NMOSD) in patients who are anti-aquaporin-4 (AQP4) 

antibody-positive with a relapsing course of the disease (see section 5.1). 
 
4.2 Posology and method of administration 
 
Soliris must be administered by a healthcare professional and under the supervision of a physician 
experienced in the management of patients with haematological, renal, neuromuscular or neuro-
inflammatory disorders. 
 
Home infusion may be considered for patients who have tolerated infusions well in the clinic. The 
decision of a patient to receive home infusions should be made after evaluation and recommendation from 
the treating physician. Home infusions should be performed by a qualified healthcare professional. 
 
 



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Posology 
 
Adult Patients: 
 
In Paroxysmal Nocturnal Haemoglobinuria (PNH): 
The PNH dosing regimen for adult patients (≥18 years of age) consists of a 4-week initial phase followed 
by a maintenance phase: 
• Initial phase: 600 mg of Soliris administered via a 25 – 45 minute (35 minutes ± 10 minutes) 

intravenous infusion every week for the first 4 weeks. 
• Maintenance phase: 900 mg of Soliris administered via a 25 – 45 minute (35 minutes ± 10 minutes) 

intravenous infusion for the fifth week, followed by 900 mg of Soliris administered via a 25 – 
45 minute (35 minutes ± 10 minutes) intravenous infusion every 14 ± 2 days (see section 5.1). 

 
In atypical Haemolytic Uremic Syndrome (aHUS), refractory generalized Myasthenia Gravis (gMG) and 
Neuromyelitis Optica Spectrum Disorder (NMOSD): 
The aHUS, refractory gMG and NMOSD dosing regimen for adult patients (≥18 years of age) consists of 
a 4 week initial phase followed by a maintenance phase: 
• Initial phase: 900 mg of Soliris administered via a 25 – 45 minute (35 minutes ± 10 minutes) 

intravenous infusion every week for the first 4 weeks. 
• Maintenance phase: 1,200 mg of Soliris administered via a 25 – 45 minute (35 minutes ± 10 

minutes) intravenous infusion for the fifth week, followed by 1,200 mg of Soliris administered via 
a 25 – 45 minute (35 minutes ± 10 minutes) intravenous infusion every 14 ± 2 days (see section 
5.1). 

 
Paediatric patients in PNH and aHUS: 
Paediatric PNH and aHUS patients with body weight ≥ 40 kg are treated with the adult dosing 
recommendations, respectively.   
 
In paediatric PNH and aHUS patients with body weight below 40 kg, the Soliris dosing regimen consists 
of: 

Patient Body 
Weight 

Initial Phase Maintenance Phase 

30 to <40 kg 600 mg weekly x 2 900 mg at week 3; then 900 mg every 2 weeks 
20 to <30 kg 600 mg weekly x 2 600 mg at week 3; then 600 mg every 2 weeks 
10 to <20 kg 600 mg weekly x 1 300 mg at week 2; then 300 mg every 2 weeks 
5 to <10 kg 300 mg weekly x 1 300 mg at week 2; then 300 mg every 3 weeks 

 
Soliris has not been studied in patients with PNH who weigh less than 40kg. The posology of Soliris for 
PNH patients less than 40kg weight is based on the posology used for patients with aHUS and who weigh 
less than 40kg. 
 
Soliris has not been studied in paediatric patients with refractory gMG or NMOSD. 
 
For adult aHUS, refractory gMG and NMOSD patients and paediatric aHUS patients supplemental dosing 
of Soliris is required in the setting of concomitant PE/PI (plasmapheresis or plasma exchange, or fresh 
frozen plasma infusion): 
 
 
 
 
 



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Type of Plasma 
Intervention 

Most Recent 
Soliris Dose 

Supplemental Soliris 
Dose With Each PE/PI 
Intervention 

Timing of 
Supplemental Soliris 
Dose 

Plasmapheresis or plasma 
exchange 

300 mg 300 mg per each 
plasmapheresis or 
plasma exchange 
session 

 
 
Within 60 minutes after 
each plasmapheresis or 
plasma exchange ≥600 mg 600 mg per each 

plasmapheresis or 
plasma exchange 
session 

Fresh frozen plasma 
infusion 

≥300 mg 300 mg per infusion of 
fresh frozen plasma 

60 minutes prior to each 
infusion of fresh frozen 
plasma  

 
Treatment monitoring 
aHUS patients should be monitored for signs and symptoms of thrombotic microangiopathy (TMA) (see 
section 4.4 aHUS laboratory monitoring). 
Soliris treatment is recommended to continue for the patient’s lifetime, unless the discontinuation of 
Soliris is clinically indicated (see section 4.4). 
 
Elderly 
Soliris may be administered to patients aged 65 years and over. There is no evidence to suggest that any 
special precautions are needed when older people are treated – although experience with Soliris in this 
patient population is still limited. 
 
Renal impairment 
No dose adjustment is required for patients with renal impairment (see section 5.1). 
 
Hepatic impairment 
The safety and efficacy of Soliris have not been studied in patients with hepatic impairment. 
 
Method of administration 
Do not administer as an intravenous push or bolus injection. Soliris should only be administered via 
intravenous infusion as described below. 
 
For instructions on dilution of the medicinal product before administration, see section 6.6. 
The diluted solution of Soliris should be administered by intravenous infusion over 25 – 45 minutes (35 
minutes ± 10 minutes) in adults and 1-4 hours in paediatric patients under 18 years of age via gravity feed, 
a syringe-type pump, or an infusion pump. It is not necessary to protect the diluted solution of Soliris from 
light during administration to the patient. 
Patients should be monitored for one hour following infusion. If an adverse event occurs during the 
administration of Soliris, the infusion may be slowed or stopped at the discretion of the physician. If the 
infusion is slowed, the total infusion time may not exceed two hours in adults and four hours in paediatric 
patients under 18 years of age. 
 
There is limited safety data supporting home-based infusions, additional precautions in the home setting 
such as availability of emergency treatment of infusion reactions or anaphylaxis are recommended. 
Infusion reactions are described in Sections 4.4 and 4.8 on the SmPC. 
 



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Refractory gMG 
Available data suggest that clinical response is usually achieved by 12 weeks of Soliris treatment. 
Discontinuation of the therapy should be considered in a patient who shows no evidence of therapeutic 
benefit by 12 weeks. 
 
4.3 Contraindications 
 
Hypersensitivity to eculizumab, murine proteins or to any of the excipients listed in section 6.1. 
 
Soliris therapy must not be initiated in patients (see section 4.4): 

- with unresolved Neisseria meningitidis infection 
- who are not currently vaccinated against Neisseria meningitidis unless they receive prophylactic 

treatment with appropriate antibiotics until 2 weeks after vaccination. 
 
4.4 Special warnings and precautions for use 
 
Soliris is not expected to affect the aplastic component of anaemia in patients with PNH. 
 
Meningococcal Infection 
Due to its mechanism of action, the use of Soliris increases the patient’s susceptibility to meningococcal 
infection (Neisseria meningitidis). Meningococcal disease due to any serogroup may occur. To reduce the 
risk of infection, all patients must be vaccinated at least 2 weeks prior to receiving Soliris unless the risk 
of delaying Soliris therapy outweighs the risks of developing a meningococcal infection. Patients who 
initiate Soliris treatment less than 2 weeks after receiving a tetravalent meningococcal vaccine must 
receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Vaccines 
against serogroups A, C, Y, W 135 and B where available, are recommended in preventing the commonly 
pathogenic meningococcal serogroups. Patients must receive vaccination according to current national 
vaccination guidelines for vaccination use.  
 
Vaccination may further activate complement. As a result, patients with complement-mediated diseases, 
including PNH, aHUS, refractory gMG and NMOSD, may experience increased signs and symptoms of 
their underlying disease, such as haemolysis (PNH), TMA (aHUS), MG exacerbation (refractory gMG) or 
relapse (NMOSD). Therefore, patients should be closely monitored for disease symptoms after 
recommended vaccination. 
 
Vaccination may not be sufficient to prevent meningococcal infection. Consideration should be given to 
official guidance on the appropriate use of antibacterial agents. Cases of serious or fatal meningococcal 
infections have been reported in Soliris-treated patients. Sepsis is a common presentation of 
meningococcal infections in patients treated with Soliris (see section 4.8). All patients should be 
monitored for early signs of meningococcal infection, evaluated immediately if infection is suspected, and 
treated with appropriate antibiotics if necessary. Patients should be informed of these signs and symptoms 
and steps taken to seek medical care immediately. Physicians must discuss the benefits and risks of Soliris 
therapy with patients and provide them with a patient information brochure and a patient safety card (see 
Package Leaflet for a description).  
 
Other Systemic Infections 
Due to its mechanism of action, Soliris therapy should be administered with caution to patients with active 
systemic infections. Patients may have increased susceptibility to infections, especially with Neisseria and 
encapsulated bacteria. Serious infections with Neisseria species (other than Neisseria meningitidis), 
including disseminated gonococcal infections, have been reported. 
Patients should be provided with information from the Package Leaflet to increase their awareness of 
potential serious infections and the signs and symptoms of them. Physicians should advise patients about 
gonorrhoea prevention. 



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Infusion Reactions 
Administration of Soliris may result in infusion reactions or immunogenicity that could cause allergic or 
hypersensitivity reactions (including anaphylaxis). In clinical trials, 1 (0.9%) gMG patient experienced an 
infusion reaction which required discontinuation of Soliris. No PNH, aHUS or NMOSD patients 
experienced an infusion reaction which required discontinuation of Soliris. Soliris administration should 
be interrupted in all patients experiencing severe infusion reactions and appropriate medical therapy 
administered. 
 
Immunogenicity 
Infrequent antibody responses have been detected in Soliris-treated patients across all clinical studies. In 
PNH placebo controlled studies low antibody responses have been reported with a frequency (3.4%) 
similar to that of placebo (4.8%).  
In patients with aHUS treated with Soliris, antibodies to Soliris were detected in 3/100 (3%) by the ECL 
bridging format assay. 1/100 (1%) aHUS patients had low positive values for neutralizing antibodies. 
In a refractory gMG placebo controlled study, none (0/62) of the Soliris treated patients showed antidrug 
antibody response during the 26 week active treatment, whereas in a refractory gMG extension study, a 
total of 2.6% overall were positive for ADAs at any post-baseline visit. Positive ADA results appeared to 
be transient, as positive titers were not observed at subsequent visits, and there were no clinical findings in 
these patients suggestive of an effect of positive ADA titers. 
In a NMOSD placebo controlled study, 2/95 (2.1%) of the Soliris treated patients showed antidrug 
antibody response post-baseline. Both patients were negative for neutralizing antibodies. Positive ADA 
samples were low titer and transient. There has been no observed correlation of antibody development to 
clinical response or adverse events. 
 
Immunization 
Prior to initiating Soliris therapy, it is recommended that PNH, aHUS, refractory gMG  and NMOSD 
patients initiate immunizations according to current immunization guidelines. Additionally, all patients 
must be vaccinated against meningococcal infections at least 2 weeks prior to receiving Soliris unless the 
risk of delaying Soliris therapy outweighs the risks of developing a meningococcal infection. Patients who 
initiate Soliris treatment less than 2 weeks after receiving a tetravalent meningococcal vaccine must 
receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Vaccines 
against serogroups A, C, Y, W 135 and B where available are recommended in preventing the commonly 
pathogenic meningococcal serogroups. (see Meningococcal Infection). 
 
Patients less than 18 years of age must be vaccinated against Haemophilus influenzae and pneumococcal 
infections, and strictly need to adhere to the national vaccination recommendations for each age group. 
 
Vaccination may further activate complement. As a result, patients with complement-mediated diseases, 
including PNH, aHUS, refractory gMG and NMOSD may experience increased signs and symptoms of 
their underlying disease, such as haemolysis (PNH), TMA (aHUS), MG exacerbation (refractory gMG) or 
relapse (NMOSD). Therefore, patients should be closely monitored for disease symptoms after 
recommended vaccination. 
 
Anticoagulant therapy 
Treatment with Soliris should not alter anticoagulant management.  
 
Immunosuppressant and anticholinesterase therapies 
 
Refractory gMG 
When immunosuppressant and anticholinesterase therapies are decreased or discontinued, patients should 
be monitored closely for signs of disease exacerbation.  
 



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Neuromyelitis Optica Spectrum Disorder 
When immunosuppressant therapy is decreased or discontinued, patients should be monitored closely for 
signs and symptoms of potential NMOSD relapse. 
 
. 
PNH Laboratory Monitoring 
PNH patients should be monitored for signs and symptoms of intravascular haemolysis, including serum 
lactate dehydrogenase (LDH) levels. PNH patients receiving Soliris therapy should be similarly monitored 
for intravascular haemolysis by measuring LDH levels, and may require dose adjustment within the 
recommended 14±2 day dosing schedule during the maintenance phase (up to every 12 days).  
 
aHUS Laboratory Monitoring 
aHUS patients receiving Soliris therapy should be monitored for thrombotic microangiopathy by 
measuring platelet counts, serum LDH and serum creatinine, and may require dose adjustment within the 
recommended 14±2 day dosing schedule during the maintenance phase (up to every 12 days). 
 
Treatment Discontinuation for PNH 
If PNH patients discontinue treatment with Soliris they should be closely monitored for signs and 
symptoms of serious intravascular haemolysis. Serious haemolysis is identified by serum LDH levels 
greater than the pre-treatment level, along with any of the following: greater than 25% absolute decrease 
in PNH clone size (in the absence of dilution due to transfusion) in one week or less; a haemoglobin level 
of <5 g/dL or a decrease of >4 g/dL in one week or less; angina; change in mental status; a 50% increase 
in serum creatinine level; or thrombosis. Monitor any patient who discontinues Soliris for at least 8 weeks 
to detect serious haemolysis and other reactions. 
If serious haemolysis occurs after Soliris discontinuation, consider the following procedures/treatments: 
blood transfusion (packed RBCs), or exchange transfusion if the PNH RBCs are >50% of the total RBCs 
by flow cytometry; anticoagulation; corticosteroids; or reinstitution of Soliris. In PNH clinical studies, 16 
patients discontinued the Soliris treatment regimen. Serious haemolysis was not observed. 
 
Treatment Discontinuation for aHUS 
Thrombotic microangiopathy (TMA) complications have been observed as early as 4 weeks and up to 127 
weeks following discontinuation of Soliris treatment in some patients. Discontinuation of treatment should 
only be considered if medically justified. 
 
In aHUS clinical studies, 61 patients (21 paediatric patients) discontinued Soliris treatment with a median 
follow-up period of 24 weeks. Fifteen severe thrombotic microangiopathy (TMA) complications in 12 
patients were observed following treatment discontinuation, and 2 severe TMA complications occurred in 
an additional 2 patients that received a reduced dosing regimen of Soliris outside of the approved dosing 
regimen (See Section 4.2).  Severe TMA complications occurred in patients regardless of whether they 
had an identified genetic mutation, high risk polymorphism or auto-antibody. Additional serious medical 
complications occurred in these patients including severe worsening of kidney function, disease-related 
hospitalization and progression to end stage renal disease requiring dialysis. Despite Soliris re-initiation 
following discontinuation, progression to end stage renal disease occurred in one patient.  
 
If aHUS patients discontinue treatment with Soliris, they should be monitored closely for signs and 
symptoms of severe thrombotic microangiopathy complications. Monitoring may be insufficient to predict 
or prevent severe thrombotic microangiopathy complications in patients with aHUS after discontinuation 
of Soliris. 
Severe thrombotic microangiopathy complications post discontinuation can be identified by (i)  any two, 
or repeated measurement of any one, of the following: a decrease in platelet count of 25% or more as 
compared to either baseline or to peak platelet count during Soliris treatment; an increase in serum 
creatinine of 25% or more as compared to baseline or to nadir during Soliris treatment; or, an increase in 



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serum LDH of 25% or more as compared to baseline or to nadir during Soliris treatment; or (ii) any one of 
the following: a change in mental status or seizures; angina or dyspnoea; or thrombosis. 
 
If severe thrombotic microangiopathy complications occur after Soliris discontinuation, consider 
reinstitution of Soliris treatment, supportive care with PE/PI, or appropriate organ-specific supportive 
measures including renal support with dialysis, respiratory support with mechanical ventilation or 
anticoagulation.   
 
Treatment discontinuation for refractory gMG:  
Use of Soliris in refractory gMG treatment has been studied only in the setting of chronic administration. 
Patients who discontinue Soliris treatment should be carefully monitored for signs and symptoms of 
disease exacerbation. 
 
Treatment discontinuation for NMOSD: 
Use of Soliris in NMOSD treatment has been studied only in the setting of chronic administration 
and the effect of Soliris discontinuation has not been characterized. Patients who discontinue 
Soliris treatment should be carefully monitored for signs and symptoms of potential NMOSD 
relapse. 
 
Educational materials 
All physicians who intend to prescribe Soliris must ensure they are familiar with the physician’s guide to 
prescribing. Physicians must discuss the benefits and risks of Soliris therapy with patients and provide 
them with a patient information brochure and a patient safety card.  
Patients should be instructed that if they develop fever, headache accompanied with fever and/or stiff neck 
or sensitivity to light, they should immediately seek medical care as these signs may be indicative of 
meningococcal infection. 
 
Excipients 
This medicinal product contains 5 mmol sodium per vial. It should be taken into consideration by patients 
on a controlled sodium diet. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. Based on the potential inhibitory effect of eculizumab on 
complement-dependent cytotoxicity of rituximab, eculizumab may reduce the expected pharmacodynamic 
effects of rituximab. 
 
Chronic intravenous human immunoglobulin (IVIg) treatment may interfere with the endosomal neonatal 
Fc receptor (FcRn) recycling mechanism of monoclonal antibodies such as eculizumab and thereby decrease 
serum eculizumab concentrations. 
 
4.6 Fertility, pregnancy and lactation 
 
The use of adequate contraception to prevent pregnancy and for at least 5 months after the last dose of 
treatment with eculizumab should be considered for women of childbearing potential. 

Pregnancy 
There are no well-controlled studies in pregnant women treated with eculizumab. Data on a limited 
number of pregnancies exposed to eculizumab (less than 300 pregnancy outcomes) indicate there is no 
increased  risk of foetal malformation or foetal-neonatal toxicity. However, due to the lack of well-
controlled studies, uncertainties remain. Therefore, an individual risk benefit analysis is recommended 
before starting and during treatment with eculizumab in pregnant women. Should such a treatment be 



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considered necessary during pregnancy, a close maternal and foetal monitoring according to local 
guidelines is recommended. 
 
Animal reproduction studies have not been conducted with eculizumab (see section 5.3).  
 
Human IgG are known to cross the human placental barrier, and thus eculizumab may potentially cause 
terminal complement inhibition in the foetal circulation. Therefore, Soliris should be given to a pregnant 
woman only if clearly needed.  
 
Breast-feeding 
No effects on the breastfed newborn / infant are anticipated as limited data available suggest that 
eculizumab is not excreted in human breast milk. However, due to the limitations of the available data, the 
developmental and health benefits of breastfeeding should be considered along with the mother’s clinical 
need for eculizumab and any potential adverse effects on the breastfed child from eculizumab or from the 
underlying maternal condition. 
 
Fertility 
No specific study of eculizumab on fertility has been conducted. 
 
4.7 Effects on ability to drive and use machines 
 
Soliris has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
Supportive safety data were obtained from 31 completed clinical studies that included 1,503 patients 
exposed to eculizumab in complement-mediated disease populations, including PNH, aHUS, refractory 
gMG and NMOSD. The most common adverse reaction was headache, (occurred mostly in the initial 
phase of dosing), and the most serious adverse reaction was meningococcal sepsis. 

 
Tabulated list of adverse reactions  
Table 1 gives the adverse reactions observed from spontaneous reporting and in eculizumab completed 
clinical trials, including PNH, aHUS, refractory gMG and NMOSD studies. Adverse reactions reported at 
a very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100) or rare 
(≥1/10,000 to <1/1,000) frequency with eculizumab, are listed by system organ class and preferred term. 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
  



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Table 1: Adverse Reactions reported in eculizumab clinical trials, including patients with PNH, 
aHUS, refractory gMG and NMOSD as well as from postmarketing experience 
MedDRA System 
Organ Class 
 

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) 

Infection and 
infestations 

 Pneumonia, Upper 
respiratory tract 
infection, 
Bronchitis, 
Nasopharyngitis, 
Urinary tract 
infection, Oral 
Herpes  

Meningococcal 
infectionb, Sepsis, 
Septic shock, 
Peritonitis, Lower 
respiratory tract 
infection, Fungal 
infection, Viral 
infection, Abscessa, 
Cellulitis, Influenza, 
Gastrointestinal 
infection, Cystitis, 
Infection, Sinusitis,  

Aspergillus infectionc, 
Arthritis bacterialc, 
Genitourinary tract 
gonococcal infection,  
Haemophilus influenzae 
infection,  
Impetigo,  
Gingivitis  

Neoplasms benign, 
malignant and 
unspecified 
(including cysts and 
polyps) 

   Malignant melanoma, 
Myelodysplastic syndrome  

Blood and lymphatic 
system disorders 

 Leukopenia, 
Anaemia  

Thrombocytopenia, 
Lymphopenia  

Haemolysis*, Abnormal 
clotting factor, Red blood 
cell agglutination, 
Coagulopathy  

Immune system 
disorders 

  Anaphylactic reaction, 
Hypersensitivity  

 

Endocrine disorders    Basedow’s disease  
Metabolism and 
nutrition disorders 

  Decreased appetite   

Psychiatric disorders  Insomnia  Depression, Anxiety, 
Mood swings  

Abnormal dreams, Sleep 
disorder  

Nervous system 
disorders 

Headache  Dizziness, 
Dysgeusia  

Paraesthesia, Tremor Syncope  

Eye disorders   Vision blurred  Conjunctival irritation  
Ear and labyrinth 
disorders 

  Tinnitus, Vertigo   

Cardiac disorders   Palpitation   
Vascular disorders  Hypertension Accelerated 

hypertension, 
Hypotension, Hot 
flush, Vein disorder  

Haematoma 

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Cough, 
Oropharyngeal pain 

Dyspnoea, Epistaxis, 
Throat irritation, Nasal 
congestion, 
Rhinorrhoea 

 

Gastrointestinal 
disorders 

 Diarrhoea, 
Vomiting, Nausea, 
Abdominal pain 

Constipation, 
Dyspepsia, Abdominal 
distension  

Gastroesophageal reflux 
disease, Gingival pain 

Hepatobiliary 
disorders 

   Jaundice  

Skin and 
subcutaneous tissue 
disorders 

 Rash, Pruritus, 
Alopecia 

Urticaria, Erythema, 
Petechiae, 
Hyperhidrosis, Dry 
skin 

Dermatitis, Skin 
depigmentation 



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Musculoskeletal and 
connective tissue 
disorders 

 Arthralgia, Myalgia,  Muscle spasms, Bone 
pain, Back pain, Neck 
pain, Joint swelling, 
Pain in extremity 

Trismus  

Renal and urinary 
disorders 

  Renal impairment, 
Dysuria, Haematuria 

 

Reproductive system 
and breast disorders 

  Spontaneous penile 
erection,  

Menstrual disorder 

General disorders 
and administration 
site conditions 

 Pyrexia, Fatigue, 
Influenza like illness 

Edema, Chest 
discomfort, Asthenia, 
Chest pain, Infusion 
site pain, Chills 

Extravasation, Infusion site 
paraesthesia, Feeling hot  

Investigations   Alanine 
aminotransferase 
increased, Aspartate 
aminotransferase 
increased, Gamma-
glutamyltransferase 
increased, Haematocrit 
decreased, 
Haemoglobin 
decreased 

Coombs test positivec  

Injury, poisoning 
and procedural 
complication 
 

  Infusion related 
reaction 

 

Included Studies: Asthma (C07-002), aHUS(C08-002, C08-003, C10-003, C10-004), Dermatomyositis (C99-006), 
gMG (C08-001, ECU-MG-301, ECU-MG-302), Neuromyelitis Optica Spectrum Disorder (ECU-NMO-301), IMG 
(C99-004, E99-004), PNH (C02-001, C04-001, C04-002, C06-002, C07-001, E02-001, E05-001, E07-001, M07-005, 
X03-001, X03-001A), Psoriasis (C99-007), RA (C01-004, C97-001, C99-001, E01-004, E99-001), STEC-HUS 
(C11-001), SLE (C97-002). MedDRA version 21.0. 
*See paragraph Description of selected adverse reactions. 
a Abscess includes the following group of PTs: Abscess limb, Colonic abscess, Renal abscess, Subcutaneous abscess, 
Tooth abscess, Hepatosplenic abscess, Perirectal abscess, Rectal abscess. 
b Meningococcal infection includes the following group of PTs: Meningococcal infection, Meningococcal sepsis, 
Meningitis meningococcal, Neisseria infection. 
cADRs identified in postmarketing reports 
 
Description of selected adverse reactions 
In all clinical studies, the most serious adverse reaction was meningococcal sepsis which is a common 
presentation of meningococcal infections in patients treated with Soliris (see section 4.4).  
Other cases of Neisseria species have been reported including sepsis with Neisseria gonorrhoeae, 
Neisseria sicca/subflava, Neisseria spp unspecified. 
 
Antibodies to Soliris were detected in 2% of patients with PNH using an ELISA assay, 3% of patients 
with aHUS and 2% of patients with NMOSD using the ECL bridging format assay. In refractory gMG 
placebo-controlled studies, no antidrug antibodies were observed. As with all proteins there is a potential 
for immunogenicity. 
 
Cases of haemolysis have been reported in the setting of missed or delayed Soliris dose in PNH clinical 
trials (see also Section 4.4). 
 
Cases of thrombotic microangiopathy complication have been reported in the setting of missed or delayed 
Soliris dose in aHUS clinical trials (see also Section 4.4). 
 
 



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Paediatric population  
In children and adolescent PNH patients (aged 11 years to less than 18 years) included in the paediatric 
PNH Study M07-005, the safety profile appeared similar to that observed in adult PNH patients. The most 
common adverse reaction reported in paediatric patients was headache.  
 
In paediatric aHUS patients (aged 2 months to less than 18 years) included in the aHUS studies C08-002, 
C08-003, C09-001r and C10-003, the safety profile appeared similar to that observed in adult aHUS 
patients. The safety profiles in the different paediatric subsets of age appear similar. 
 
Soliris has not been studied in paediatric patients with refractory gMG or NMOSD. 
 
Elderly population 
No overall differences in safety were reported between elderly (≥ 65 years) and younger refractory gMG 
patients (< 65 years) (see section 5.1).  
 
Patients with other diseases 
Safety Data from Other Clinical Studies  
Supportive safety data were obtained in 12 completed clinical studies that included 934 patients exposed 
to eculizumab in other disease populations other than PNH, aHUS, refractory gMG or NMOSD. There 
was an un-vaccinated patient diagnosed with idiopathic membranous glomerulonephropathy who 
experienced meningococcal meningitis. Adverse reactions reported in patients with disease other than 
PNH, aHUS, refractory gMG or NMOSD were similar to those reported in patients with PNH, aHUS, 
refractory gMG or NMOSD (see Table 1 above). No specific adverse reactions have emerged from these 
clinical studies. 
 
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 case of overdose has been reported. 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Selective immunosuppressants, ATC code: L04AA25 
 
Soliris is a recombinant humanised monoclonal IgG2/4k antibody that binds to the human C5 complement 
protein and inhibits the activation of terminal complement. The Soliris antibody contains human constant 
regions and murine complementarity-determining regions grafted onto the human framework light- and 
heavy-chain variable regions. Soliris is composed of two 448 amino acid heavy chains and two 214 amino 
acid light chains and has a molecular weight of approximately 148 kDa. 
 
Soliris is produced in a murine myeloma (NS0 cell line) expression system and purified by affinity and ion 
exchange chromatography. The bulk drug substance manufacturing process also includes specific viral 
inactivation and removal steps. 
 
 
 

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Mechanism of action 
 
Eculizumab, the active ingredient in Soliris, is a terminal complement inhibitor that specifically binds to 
the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and 
preventing the generation of the terminal complement complex C5b-9. Eculizumab preserves the early 
components of complement activation that are essential for opsonization of microorganisms and clearance 
of immune complexes. 
 
In PNH patients, uncontrolled terminal complement activation and the resulting complement-mediated 
intravascular haemolysis are blocked with Soliris treatment.   
In most PNH patients, eculizumab serum concentrations of approximately 35 microgram/mL are sufficient 
for essentially complete inhibition of terminal complement-mediated intravascular haemolysis. 
In PNH, chronic administration of Soliris resulted in a rapid and sustained reduction in complement-
mediated haemolytic activity.   
 
In aHUS patients, uncontrolled terminal complement activation and the resulting complement-mediated 
thrombotic microangiopathy are blocked with Soliris treatment.   
All patients treated with Soliris when administered as recommended demonstrated rapid and sustained 
reduction in terminal complement activity. In all aHUS patients, eculizumab serum concentrations of 
approximately 50 - 100 microgram/mL are sufficient for essentially complete inhibition of terminal 
complement activity.  
In aHUS, chronic administration of Soliris resulted in a rapid and sustained reduction in complement-
mediated thrombotic microangiopathy. 
 
In refractory gMG patients, uncontrolled terminal complement activation causes membrane attack 
complex (MAC) dependent lysis and C5a-dependent inflammation at the Neuromuscular Junction (NMJ) 
leading to failure of neuromuscular transmission. Chronic administration of Soliris results in immediate, 
complete, and sustained inhibition of terminal complement activity (eculizumab serum concentrations ≥ 
116 microgram/ml). 
 
In patients with NMOSD, uncontrolled terminal complement activation caused by autoantibodies against 
AQP4 leads to the formation of the MAC and C5a-dependent inflammation which results in astrocyte 
necrosis and increased permeability of the blood brain barrier, as well as death of the surrounding 
oligodendrocytes and neurons. Chronic administration of Soliris results in immediate, complete, and 
sustained inhibition of terminal complement activity (eculizumab serum concentrations ≥ 116 
microgram/ml). 
 
Clinical efficacy and safety 
 
Paroxysmal Nocturnal Haemoglobinuria 
 
The safety and efficacy of Soliris in PNH patients with haemolysis were assessed in a randomized, 
double-blind, placebo-controlled 26 week study (C04-001).  PNH patients were also treated with Soliris in 
a single arm 52 week study (C04-002), and in a long term extension study (E05-001). Patients received 
meningococcal vaccination prior to receipt of Soliris. In all studies, the dose of eculizumab was 600 mg 
every 7 ± 2 days for 4 weeks, followed by 900 mg 7 ± 2 days later, then 900 mg every 14 ± 2 days for the 
study duration. Soliris was administered as an intravenous infusion over 25 – 45 minutes (35 minutes ± 10 
minutes). An observational non-interventional Registry in patients with PNH (M07-001) was also initiated 
to characterize the natural history of PNH in untreated patients and the clinical outcomes during Soliris 
treatment. 
 



14 

In study C04-001 (TRIUMPH) PNH patients with at least 4 transfusions in the prior 12 months, flow 
cytometric confirmation of at least 10% PNH cells and platelet counts of at least 100,000/microliter were 
randomized to either Soliris (n = 43) or placebo (n = 44). Prior to randomization, all patients underwent an 
initial observation period to confirm the need for RBC transfusion and to identify the haemoglobin 
concentration (the "set-point") which would define each patient’s haemoglobin stabilization and 
transfusion outcomes. The haemoglobin set-point was less than or equal to 9 g/dL in patients with 
symptoms and was less than or equal to 7 g/dL in patients without symptoms. Primary efficacy endpoints 
were haemoglobin stabilization (patients who maintained a haemoglobin concentration above the 
haemoglobin set-point and avoid any RBC transfusion for the entire 26 week period) and blood 
transfusion requirement. Fatigue and health-related quality of life were relevant secondary endpoints. 
Haemolysis was monitored mainly by the measurement of serum LDH levels, and the proportion of PNH 
RBCs was monitored by flow cytometry. Patients receiving anticoagulants and systemic corticosteroids at 
baseline continued these medications. Major baseline characteristics were balanced (see Table 2).  
 
In the non-controlled study C04-002 (SHEPHERD), PNH patients with at least one transfusion in the prior 
24 months and at least 30,000 platelets/microliter received Soliris over a 52-week period. Concomitant 
medications included anti-thrombotic agents in 63% of the patients and systemic corticosteroids in 40% of 
the patients.  Baseline characteristics are shown in Table 2.  
 
Table 2: Patient Demographics and Characteristics in C04-001 and C04-002  

 C04-001 C04-002 

Parameter Placebo N = 44 
Soliris 
N = 43 

Soliris 
N = 97 

Mean Age (SD) 38.4 (13.4) 42.1 (15.5) 41.1 (14.4) 
Gender - Female (%) 29 (65.9) 23 (53.5) 49 (50.5) 
History of Aplastic Anaemia or MDS (%) 12 (27.3) 8 (18.7) 29 (29.9) 
Concomitant Anticoagulants (%) 20 (45.5) 24 (55.8) 59 (61) 
Concomitant Steroids/Immunosuppressant 
Treatments (%) 16 (36.4) 14 (32.6) 46 (47.4) 

Discontinued treatment 10 2 1 
PRBC in previous 12 months (median 
(Q1,Q3)) 17.0 (13.5, 25.0) 

18.0 (12.0, 
24.0) 8.0 (4.0, 24.0) 

Mean Hgb level (g/dL) at setpoint (SD) 7.7 (0.75) 7.8 (0.79) N/A 
Pre-treatment LDH levels (median, U/L) 2,234.5 2,032.0 2,051.0 
Free Haemoglobin at baseline (median, 
mg/dL)  

46.2 40.5 34.9 

 
In TRIUMPH, study patients treated with Soliris had significantly reduced (p< 0.001) haemolysis 
resulting in improvements in anaemia as indicated by increased haemoglobin stabilization and reduced 
need for RBC transfusions compared to placebo treated patients (see Table 3). These effects were seen 
among patients within each of the three pre-study RBC transfusion strata (4 - 14 units; 15 - 25 units; 
> 25 units). After 3 weeks of Soliris treatment, patients reported less fatigue and improved health-related 
quality of life. Because of the study sample size and duration, the effects of Soliris on thrombotic events 
could not be determined. In SHEPHERD study, 96 of the 97 enrolled patients completed the study (one 
patient died following a thrombotic event). A reduction in intravascular haemolysis as measured by serum 
LDH levels was sustained for the treatment period and resulted in increased transfusion avoidance, a 
reduced need for RBC transfusion and less fatigue. See Table 3. 
 



15 

Table 3: Efficacy Outcomes in C04-001 and C04-002  
 C04-001 C04-002* 
 Placebo 

N = 44 
Soliris 
N = 43 P – Value 

Soliris 
N = 97 P – Value 

Percentage of patients with 
stabilized Haemoglobin levels 
at end of study 

0 49 < 0.001 N/A 

PRBC transfused during 
treatment (median) 10 0 < 0.001 0 < 0.001 

Transfusion Avoidance during 
treatment (%) 0 51 < 0.001 51 < 0.001 

LDH levels at end of study 
(median, U/L) 2,167 239 < 0.001 269 < 0.001 

LDH AUC at end of study 
(median, U/L x Day) 411,822 58,587 < 0.001 -632,264 < 0.001 

Free Haemoglobin at end of 
study (median, mg/dL) 62 5 < 0.001 5 < 0.001 

FACIT-Fatigue (effect size)  1.12 < 0.001 1.14 < 0.001 
* Results from study C04-002 refer to pre- versus post-treatment comparisons. 
 
From the 195 patients that originated in C04-001, C04-002 and other initial studies, Soliris-treated PNH 
patients were enrolled in a long term extension study (E05-001). All patients sustained a reduction in 
intravascular haemolysis over a total Soliris exposure time ranging from 10 to 54 months. There were 
fewer thrombotic events with Soliris treatment than during the same period of time prior to treatment. 
However, this finding was shown in non-controlled clinical trials. 

The PNH registry (M07-001) was used to evaluate the efficacy of Soliris in PNH patients with no history 
of RBC transfusion. These patients had high disease activity as defined by elevated haemolysis (LDH 
≥1.5x ULN) and the presence of  related clinical symptom(s): fatigue, haemoglobinuria, abdominal pain, 
shortness of breath (dyspnoea), anaemia (haemoglobin <100 g/L), major adverse vascular event (including 
thrombosis), dysphagia, or erectile dysfunction.  

In the PNH Registry, patients treated with Soliris were observed to have a reduction in haemolysis and 
associated symptoms. At 6 months, patients treated with Soliris with no history of RBC transfusion had 
significantly (p<0.001) reduced LDH levels (median LDH of 305 U/L; Table 4). Furthermore, 74% of the 
patients without a history of transfusion and treated with Soliris experienced clinically meaningful 
improvements in FACIT-Fatigue score (i.e., increase by 4 points or more) and 84% in EORTC fatigue 
score (i.e., decrease by 10 points or more).  

 
 
 
 
 
 
 
 
 
 
 
 
 
 



16 

Table 4: Efficacy Outcomes (LDH level and FACIT-Fatigue) in Patients with PNH with No History 
of Transfusion in M07-001 

 M07-001  

Parameter  Soliris 
No transfusion 

LDH level at baseline 
(median , U/L)  

N=43 
1447 

LDH level at 6 months 
(median, U/L)  

N=36 
305 

FACIT-Fatigue score at baseline 
(median)  

N=25 
32 

FACIT-Fatigue score at last available 
assessment (median)  

N=31 
44 

FACIT-Fatigue is measured on a scale of 0-52, with higher values indicating less fatigue 
 
Atypical Haemolytic Uremic Syndrome 
 
Data from 100 patients in four prospective controlled studies, three in adult and adolescent patients (C08-
002A/B  C08-003A/B, C10-004) one in paediatric and adolescent patients (C10-003 ) and 30 patients in 
one retrospective study (C09-001r) were used to evaluate the efficacy of Soliris in the treatment of aHUS. 
 
Study C08-002A/B was a prospective, controlled, open-label study which accrued patients in the early 
phase of aHUS with evidence of clinical thrombotic microangiopathy manifestations with platelet count ≤ 
150 x 109/L despite PE/PI, and LDH and serum creatinine above upper limits of normal. 
Study C08-003A/B was a prospective, controlled, open-label study which accrued patients with longer 
term aHUS without apparent evidence of clinical thrombotic microangiopathy manifestations and 
receiving chronic PE/PI (≥1 PE/PI treatment every two weeks and no more than 3 PE/PI treatments/week 
for at least 8 weeks before the first dose). Patients in both prospective studies were treated with Soliris for 
26 weeks and most patients enrolled into a long-term, open-label extension study. All patients enrolled in 
both prospective studies had an ADAMTS-13 level above 5%. 
 
Patients received meningococcal vaccination prior to receipt of Soliris or received prophylactic treatment 
with appropriate antibiotics until 2 weeks after vaccination. In all studies, the dose of Soliris in adult and 
adolescent aHUS patients was 900 mg every 7 ± 2 days for 4 weeks, followed by 1,200 mg 7 ± 2 days 
later, then 1,200 mg every 14 ± 2 days for the study duration. Soliris was administered as an intravenous 
infusion over 35 minutes. The dosing regimen in paediatric patients and adolescents weighing less than 
40 kg was defined based on a pharmacokinetic (PK) simulation that identified the recommended dose and 
schedule based on body weight (see section 4.2). 
 
Primary endpoints included platelet count change from baseline in study C08-002A/B and thrombotic 
microangiopathy (TMA) event-free status in study C08-003A/B. Additional endpoints included TMA 
intervention rate, haematologic normalization, complete TMA response, changes in LDH, renal function 
and quality of life. TMA-event free status was defined as the absence for at least 12 weeks of the 
following: decrease in platelet count of > 25% from baseline, PE/PI, and new dialysis. TMA interventions 
were defined as PE/PI or new dialysis. Haematologic normalization was defined as normalization of 
platelet counts and LDH levels sustained for ≥2 consecutive measurements for ≥4 weeks. Complete TMA 
response was defined as haematologic normalization and a ≥25% reduction in serum creatinine sustained 
in ≥ 2 consecutive measurements for ≥ 4 weeks. 
Baseline characteristics are shown in Table 5.  
 



17 

Table 5: Patient Demographics and Characteristics in C08-002A/B and C08-003A/B  
Parameter C08-002A/B C08-003A/B 

Soliris  
N = 17 

Soliris  
N = 20 

Time from first diagnosis until screening in 
months, median (min, max) 

10 (0.26, 236) 48 (0.66, 286) 

Time from current clinical TMA 
manifestation until screening in months, 
median (min, max) 

< 1 (<1, 4) 9 (1, 45) 

Number of PE/PI sessions for current 
clinical TMA manifestation, median (min, 
max) 

17 (2, 37) 62 (20, 230) 

Number of PE/PI sessions in 7 days prior to 
first dose of eculizumab, median (min, max) 

6 (0, 7) 2 (1, 3) 

Baseline platelet count (× 109/L), mean (SD) 109 (32) 228 (78) 
Baseline LDH (U/L), mean (SD) 323 (138) 223 (70) 
Patients without identified mutation, n (%) 4 (24) 6 (30) 

 
Patients in aHUS Study C08-002 A/B received Soliris for a minimum of 26 weeks. After completion of 
the initial 26-week treatment period, most patients continued to receive Soliris by enrolling into an 
extension study. In aHUS Study C08-002A/B, the median duration of Soliris therapy was 
approximately100 weeks (range: 2 weeks to 145 weeks). 
A reduction in terminal complement activity and an increase in platelet count relative to baseline were 
observed after commencement of Soliris. Reduction in terminal complement activity was observed in all 
patients after commencement of Soliris. Table 6 summarizes the efficacy results for aHUS Study C08-
002A/B. All rates of efficacy endpoints improved or were maintained through 2 years of treatment. 
Complete TMA response was maintained by all responders. When treatment was continued for more than 
26 weeks, two additional patients achieved and maintained Complete TMA response due to normalization 
of LDH (1 patient) and a decrease in serum creatinine (2 patients).  
Renal function, as measured by eGFR, was improved and maintained during Soliris therapy. Four of the 
five patients who required dialysis at study entry were able to discontinue dialysis for the duration of 
Soliris treatment, and one patient developed a new dialysis requirement. Patients reported improved 
health-related quality of life (QoL). 
 
In aHUS Study C08-002A/B, responses to Soliris were similar in patients with and without identified 
mutations in genes encoding complement regulatory factor proteins. 
 
Patients in aHUS study C08-003A/B received Soliris for a minimum of 26 weeks. After completion of the 
initial 26-week treatment period, most patients continued to receive Soliris by enrolling into an extension 
study. In aHUS Study C08-003A/B, the median duration of Soliris therapy was approximately 114 weeks 
(range: 26 to 129 weeks). Table 6 summarizes the efficacy results for aHUS Study C08-003A/B. 
In aHUS Study C08-003A/B, responses to Soliris were similar in patients with and without identified 
mutations in genes encoding complement regulatory factor proteins. Reduction in terminal complement 
activity was observed in all patients after commencement of Soliris. All rates of efficacy endpoints 
improved or were maintained through 2 years of treatment. Complete TMA response was maintained by 
all responders. When treatment was continued for more than 26 weeks, six additional patients achieved 
and maintained Complete TMA response due to a decrease in serum creatinine. No patient required new 
dialysis with Soliris. Renal function, as measured by median eGFR, increased during Soliris therapy. 
 



18 

Table 6: Efficacy Outcomes in Prospective aHUS Studies C08-002A/B and C08-003A/B 
 C08-002A/B 

N=17 
C08-003A/B 

N=20 
 At 26 weeks At 2 years1 At 26 weeks At 2 years1 
Normalization of 
platelet count  
All patients, n (%)  
(95% CI) 
Patients with abnormal 
baseline, n/n (%) 

 
14 (82)  
(57-96) 

13/15 (87) 
 

 
15 (88)  
(64-99) 

13/15 (87) 

 
18 (90)  
(68-99) 
 1/3 (33) 

 
18 (90) 
(68-99) 
1/3 (33) 

TMA event-free 
status, n (%) (95% CI) 

15 (88)  
(64-99) 

15 (88) 
(64-99) 

16 (80)  
(56-94) 

19 (95)  
(75-99) 

TMA intervention rate 
     Daily pre-

eculizumab rate,     
median (min, max) 

     Daily  during-
eculizumab rate, 
median (min, max) 
P-value 

 
0.88  

(0.04, 1.59) 
 

0 (0, 0.31) 
 

P<0.0001 

 
0.88  

(0.04, 1.59) 
 

0 (0, 0.31) 
 

P<0.0001 

 
0.23  

(0.05, 1.09) 
 

0 
 

P <0.0001 

 
0.23  

(0.05, 1.09) 
 

0 
 

P<0.0001 

CKD improvement by 
≥1 stage,  
n (%) (95% CI) 

10 (59)  
(33-82) 

12 (71)  
(44-90) 

7 (35)  
(15-59) 

12 (60)  
(36-81) 

eGFR change 
mL/min/1.73 m2: 
median (range)  

20 (-1, 98) 28 (3, 82) 5 (-1, 20) 11 (-42, 30) 

eGFR improvement 
≥15 mL/min/1.73 m2, 
n (%)  (95% CI) 

   8 (47)  
(23-72) 

10 (59) 
(33-82) 

1 (5)  
(0-25) 

8 (40) 
(19-64) 

Change in Hgb > 
20g/L, n (%) (95% CI) 

11 (65)  
(38-86) 2 

13 (76) 
(50-93) 

9 (45)  
(23-68) 3 

13 (65)  
(41-85) 

Haematologic 
normalization, n (%) 
(95% CI) 

13 (76)  
(50-93) 

15 (88) 
(64-99) 

18 (90)  
(68-99) 

18 (90)  
(68-99) 

Complete TMA 
response, n (%) (95% 
CI) 

11(65)  
(38-86) 

13(76) 
(50-93) 

5 (25) 
(9-49) 

11(55) 
(32-77) 

1 At data cut off (20 April 2012) 
2 Study C08-002: 3 patients received ESA which was discontinued after eculizumab initiation 
3 Study C08-003: 8 patients received ESA which was discontinued in 3 of them during eculizumab therapy 
 

aHUS Study C10-004  enrolled 41 patients who displayed signs of thrombotic microangiopathy (TMA). In 
order to qualify for enrolment, patients were required to have a platelet count < lower limit of normal 
range (LLN), evidence of haemolysis such as an elevation in serum LDH, and serum creatinine above the 
upper limits of normal, without the need for chronic dialysis.  The median patient age was 35 (range: 18 to 
80 years). All patients enrolled in aHUS Study C10-004 had an ADAMTS-13 level above 5%. Fifty-one 
percent of patients had an identified complement regulatory factor mutation or auto-antibody. A total of 
35 patients received PE/PI prior to eculizumab. Table 7 summarizes the key baseline clinical and disease-
related characteristics of patients enrolled in aHUS C10-004. 



19 

Table 7:  Baseline Characteristics of Patients Enrolled in aHUS Study C10-004   

Parameter 
aHUS Study C10-004   

N = 41 

Time from aHUS diagnosis to first study dose  (months),  
median ( min, max) 0.79 (0.03, 311) 

Time from current clinical TMA manifestation until first 
study dose (months), median ( min, max) 0.52 (0.03, 19) 

Baseline platelet count (× 109/L), median (, min, max ) 125 (16, 332) 

Baseline LDH (U/L), median (, min, max) 375 (131, 3318) 

Baseline eGFR (mL/min/1.73m2), median (min, max) 10 (6, 53) 

 

Patients in aHUS Study C10-004 received Soliris for a minimum of 26 weeks. After completion of the 
initial 26-week treatment period, most patients elected to continue on chronic dosing. 

Reduction in terminal complement activity and an increase in platelet count relative to baseline were 
observed after commencement of Soliris. Soliris reduced signs of complement-mediated TMA activity, as 
shown by an increase in mean platelet counts from baseline to 26 weeks. In aHUS C10-004, mean (±SD) 
platelet count increased from 119 ± 66 x109/L at baseline to 200 ± 84 x109/L by one week; this effect was 
maintained through 26 weeks (mean platelet count (±SD) at week 26: 252 ± 70 x109/L). Renal function, as 
measured by eGFR, was improved during Soliris therapy. Twenty of the 24 patients who required dialysis 
at baseline were able to discontinue dialysis during Soliris treatment. Table 8 summarizes the efficacy 
results for aHUS study C10-004.  
 
Table 8: Efficacy Outcomes in Prospective aHUS Study C10-004   

 Efficacy Parameter 
aHUS Study C10-004 

(N = 41) 
At 26-weeks 

Change in platelet count through week 26 (109/L) 111 (-122, 362) 

Hematologic Normalization, n (%) 
Median duration of hematologic normalization, weeks (range) 1 

36 (88) 
46 (10, 74) 

Complete TMA response, n (%) 
Median duration of  complete TMA response, weeks (range) 1 

23 (56) 
42 (6, 74) 

TMA Event-free Status, n (%) 
95% CI 

37 (90) 
77; 97 

Daily TMA Intervention Rate, median (range)  
     Before eculizumab 
     On eculizumab treatment  

 
0.63 (0, 1.38) 

0 (0, 0.58)  

1 Through data cut-off (September 4, 2012), with median duration of Soliris therapy of 50 weeks (range: 13 
weeks to 86 weeks). 

 



20 

Longer term treatment with Soliris (median 52 weeks ranging from 15 to 126 weeks) was associated with 
an increased rate of clinically meaningful improvements in adult patients with aHUS. When Soliris 
treatment was continued for more than 26 weeks, three additional patients (63% of patients in total) 
achieved Complete TMA response and four additional patients (98% of patients in total) achieved 
hematologic normalization. At the last evaluation, 25 of 41 patients (61%) achieved eGFR improvement 
of ≥ 15 mL/min/1.73 m2 from baseline. 
 
Refractory Generalized Myasthenia Gravis 
 
Data from 139 patients in two prospective controlled studies (Studies C08-001 and ECU-MG-301), and 
one open-label extension trial (Study ECU-MG-302) were used to evaluate the efficacy of Soliris in the 
treatment of patients with refractory gMG. 
 
Study ECU-MG-301 (REGAIN) was a 26-week double-blind, randomized, placebo-controlled, multi-
center Phase 3 study of Soliris in patients who had failed previous therapies and remain symptomatic. One 
hundred and eighteen (118) of the 125 (94%) patients completed the 26-week treatment period and 
117 (94%) patients subsequently enrolled in Study ECU-MG-302, an open-label, multi-center long-term 
safety and efficacy extension study in which all patients received Soliris treatment. 
 
In Study ECU-MG-301, gMG patients with a positive serologic test for anti-AChR antibodies, MGFA 
(Myasthenia Gravis Foundation of America) clinical classification class II to IV and MG-ADL total score 
≥6 were randomized to either Soliris (n = 62) or placebo (n = 63). All patients included in the trial were 
refractory gMG patients and met the following predefined criteria: 
 
1) Failed treatment for at least one year with 2 or more immunosuppressant therapies (either in 
combination or as monotherapy), ie, patients continued to have impairment in activities of daily living 
despite immunosuppressant therapies 
 
OR 
 
2) Failed at least one immunosuppressant therapy and required chronic plasma exchange or IVIg to 
control symptoms, ie, patients require PE or IVIg on a regular basis for the management of muscle 
weakness at least every 3 months over previous 12 months. 
 
Patients received meningococcal vaccination prior to initiating treatment with Soliris or received 
prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination. In Studies ECU-MG-
301 and ECU-MG-302, the dose of Soliris in adult refractory gMG patients was 900 mg every 7 ± 2 days 
for 4 weeks, followed by 1200 mg at Week 5± 2 days, then 1,200 mg every 14 ± 2 days for the study 
duration. Soliris was administered as an intravenous infusion over 35 minutes. 
 
Table 9 presents the baseline characteristics of the refractory gMG patients enrolled in Study ECU-MG-
301. 
 
 
 
 
 
 
 
 
 
 
 



21 

Table 9: Patient Demographic and Characteristics in Study ECU-MG-301 
 Soliris (n=62) Placebo (n=63) 
Age at MG Diagnosis (years), 
Mean (min, max) 38.0 (5.9, 70.8) 38.1 (7.7, 78.0) 

Female, n (%) 41 (66.1) 41 (65.1) 
Duration of MG (years),  
Mean (min, max) 9.9 (1.3, 29.7) 9.2 (1.0, 33.8) 

Baseline MG-ADL Score   
Mean (SD) 10.5 (3.06) 9.9 (2.58) 
Median 10.0 9.0 

Baseline QMG Score   
Mean (SD) 17.3 (5.10) 16.9 (5.56) 
Median 17.0 16.0 

≥3 Prior Immunosuppressive Therapies* 
since diagnosis, n (%)  31 (50.0) 34 (54.0) 

Number of patients with prior exacerbations 
since diagnosis, n (%) 46 (74.2) 52 (82.5) 
Number of patients with prior MG crisis 
since diagnosis, n (%)  13 (21.0) 10 (15.9) 
Any prior ventilator support since diagnosis, 
n (%) 15 (24.2) 14 (22.2) 

Any prior intubation since diagnosis (MGFA 
class V), n (%) 11 ( 17.7) 9 ( 14.3) 

* Immunosuppressant’s included, but are not limited to, corticosteroids, azathioprine, mycophenolate, methotrexate , 
cyclosporine, tacrolimus, or cyclophosphamide. 
 
The primary endpoint for Study ECU-MG-301 was the change from baseline in the MG Activities of 
Daily Living Profile (MG-ADL – a patient reported outcome measure validated in gMG) total score at 
Week 26. The primary analysis of the MG-ADL was a Worst-Rank ANCOVA with a mean rank of 56.6 
for Soliris and 68.3 for placebo, based on 125 study patients (p=0.0698). 
 
The key secondary endpoint was the change from baseline in the Quantitative MG Scoring System (QMG 
– a physician reported outcome measure validated in gMG) total score at Week 26. The primary analysis 
of the QMG was a Worst-Rank ANCOVA with a mean rank of 54.7 for Soliris and 70.7 for placebo, 
based on 125 study patients  (p=0.0129). 
 
Efficacy outcomes for the pre-specified repeated measures analyses of the primary and secondary 
endpoints are provided in Table 10. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



22 

Table 10: ECU-MG-301 Efficacy Outcomes Change from Baseline to Week 26 
Efficacy 

Endpoints: Total 
score change 

from baseline at 
Week 26 

Soliris 
(n=62) 
(SEM) 

Placebo 
(n=63) 
(SEM) 

Soliris change 
relative to placebo 

– LS Mean 
Difference (95% 

CI) 

p-value (using 
repeated measures 

analysis) 

MG-ADL  -4.2 (0.49) -2.3(0.48) -1.9 
(-3.3, -0.6) 

0.0058 

QMG  -4.6 (0.60) -1.6 (0.59) -3.0 
(-4.6, -1.3) 

0.0006 

MGC  -8.1 (0.96) -4.8 (0.94) -3.4 
(-6.0, -0.7) 

0.0134 

MG-QoL-15  -12.6 (1.52) -5.4 (1.49) -7.2 
(-11.5, -3.0) 

0.0010 

SEM= Standard Error of the Mean CI= Confidence Interval, MGC= Myasthenia Gravis Composite, MG-QoL15= 
Myasthenia Gravis Qualtiy of Life 15 
 
In Study ECU-MG-301, a clinical responder in the MG-ADL total score was defined as having at least a 
3-point improvement. The proportion of clinical responders at Week 26 with no rescue therapy was 59.7% 
on Soliris compared with 39.7% on placebo (p=0.0229).  
In Study ECU-MG-301, a clinical responder in the QMG total score was defined as having at least a 5-point 
improvement. The proportion of clinical responders at Week 26 with no rescue therapy was 45.2% on Soliris 
compared with 19% on placebo (p=0.0018).  
 
Table 11 presents an overview of the patients reporting clinical deterioration and patients requiring rescue 
therapy over the 26 weeks. 
 
Table 11: Clinical deterioration and rescue therapy in ECU-MG-301 

Variable Statistic Placebo  
(N=63) 

Soliris 
(N=62) 

Total number of patients reporting clinical deterioration n (%) 15 (23.8) 6 (9.7) 
Total number of patients requiring rescue therapy n (%) 12 (19.0) 6 (9.7) 

 
Of the 125 patients enrolled in ECU-MG-301, 117 patients subsequently enrolled in a long-term extension 
study (Study ECU-MG-302), in which all received Soliris.. Patients that were previously treated with Soliris 
in Study ECU-MG-301 continued to demonstrate a sustained effect of Soliris on all measures (MG-ADL, 
QMG, MGC and MG-QoL15) over an additional 130 weeks of treatment with eculizumab in Study ECU-
MG-302. For patients who received placebo in Study ECU-MG-301 (placebo/eculizumab arm of Study 
ECU-MG-302), improvement occurred after initiating treatment with eculizumab and was maintained for 
more than 130 weeks in Study ECU-MG-302. Figure 1 presents the change from baseline in both MG-ADL 
(A) and QMG (B) after 26 weeks of treatment in Study ECU-MG-301 and after 130 weeks of treatment (n 
= 80 patients) in Study ECU-MG-302. 
 
 
 
 
 
 
 
 
 
 
 
 



23 

Figure 1: Mean changes from baseline in MG-ADL (1A) and QMG (1B) over Studies ECU-MG-301 and 
ECU-MG-302 
 
In Study ECU-MG-302, physicians had the option to adjust background immunosuppressant therapies. In 
this setting, 65.0% of patients decreased their daily dose of at least 1 immunosuppressive therapy (IST); 
43.6% of patients stopped an existing IST. The most common reason for change in IST therapy was 
improvement in MG symptoms.  
 
Twenty-two (22) (17.6%) elderly refractory gMG patients (> 65 years of age) were treated with Soliris in 
the clinical trials. No substantial differences were seen in safety and efficacy related to age. 
 
Neuromyelitis Optica Spectrum Disorder 
 
Data from 143 patients in one controlled study (Study ECU-NMO-301) and from 119 patients who 
continued in one open-label extension trial (Study ECU-NMO-302) were used to evaluate the efficacy and 
safety of Soliris in the treatment of patients with NMOSD.  
 
Study ECU-NMO-301 was a double-blind, randomized, placebo-controlled, multi-center, Phase 3 study of 
Soliris in patients with NMOSD.  
 
In Study ECU-NMO-301, patients with NMOSD with a positive serologic test for anti-AQP4 antibodies, a 
history of at least 2 relapses in last 12 months or 3 relapses in the last 24 months with at least 1 relapse in 
the 12 months prior to screening and an Expanded Disability Status Scale (EDSS) score ≤ 7, were 
randomized 2:1 to either Soliris (n = 96) or placebo (n = 47). Patients were permitted to receive 
background immunosuppressant therapies at stable dose during the study, with the exclusion of rituximab 
and mitoxantrone. 



24 

 
Patients either received meningococcal vaccination at least 2 weeks prior to initiating treatment with 
Soliris or received prophylactic treatment with appropriate antibiotics until 2 weeks after vaccination. In 
the eculizumab NMOSD clinical development program, the dose of Soliris in adult patients with NMOSD 
was 900 mg every 7 ± 2 days for 4 weeks, followed by 1200 mg at Week 5 ± 2 days, then 1200 mg every 
14 ± 2 days for the study duration. Soliris was administered as an intravenous infusion over 35 minutes. 
 
The majority (90.9%) of patients were female. Approximately half were White (49.0%). The median age 
at first dose of study drug was 45 years. 
 
Table 12: Patient Disease History and Baseline Characteristics in Study ECU-NMO-301 

Variable Statistic Placebo  (N = 47) 
Eculizumab  

(N = 96) 
Total  

(N = 143) 
NMOSD History  
Age at NMOSD Initial 
Clinical Presentation 
(years) 

Mean (SD) 38.5 (14.98) 35.8 (14.03) 36.6 (14.35) 
Median 38.0 35.5 36.0 

Min, Max 12, 73 5, 66 5, 73 
Time from NMOSD  
initial clinical 
presentation to first 
dose of study drug 
(years) 

Mean (SD) 6.601 (6.5863) 8.156 (8.5792) 7.645 (7.9894) 
Median 3.760 5.030 4.800 

Min, Max 0.51, 29.10 0.41, 44.85 0.41, 44.85 

Historical Annualized 
Relapse Rate within 
24 months prior to 
Screening 

Mean (SD) 2.07 (1.037) 1.94 (0.896) 1.99 (0.943) 
Median 1.92 1.85 1.92 

Min, Max 1.0, 6.4 1.0, 5.7 1.0, 6.4 

Baseline characteristics 
Baseline EDSS score Mean (SD) 4.26 (1.510) 4.15 (1.646) 4.18 (1.598) 

Median 4.00 4.00 4.00 
Min, Max 1.0, 6.5 1.0, 7.0 1.0, 7.0 

No IST usage at 
baseline n (%) 13 (27.7) 21 (21.9) 34 (23.8) 

Abbreviations: ARR = adjudicated relapse rate; EDSS = Expanded Disability Status Scale; IST = immunosupressant 
therapy; Max = maximum; Min = minimum; NMOSD = neuromyelitis optica spectrum disorder; SD = standard 
deviation. 
 
The primary endpoint for Study ECU-NMO-301 was the time to first on-trial relapse as adjudicated by an 
independent committee who were blinded to treatment. A significant effect on the time to first adjudicated 
On-trial Relapse was observed for eculizumab compared with placebo (relative risk reduction 94%; hazard 
ratio 0.058; p<0.0001) (Figure 2). Soliris-treated patients experienced similar improvement in time to first 
adjudicated on-trial relapse with or without concomitant IST treatment.  
 
 
 
 
 



25 

 
Figure 2: Kaplan-Meier Survival Estimates for Time to First Adjudicated On-Trial Relapse in 
Study ECU-NMO-301 – Full Analysis Set 
Note: Patients who did not experience an adjudicated On-trial Relapse were censored at the end of the Study Period.  
Stratified analyses are based on four randomization strata: 
(i) low EDSS at randomization (<=2.0), (ii) high EDSS (>=2.5 to <=7) and treatment naive at randomization, (iii) high 
EDSS (>=2.5 to <=7) and continuing on the same IST(s) since last relapse at randomization, (iv) high EDSS (>=2.5 
to <=7) and changes in IST(s) since last relapse at randomization. 
1 Based on the Kaplan-Meier product limit method. 
2 Based on the complementary log-log transformation. 
3 Based on a stratified log-rank test. 
4 Based on a stratified Cox proportional hazards model. 
5 Wald confidence interval. 
Abbreviations: CI = confidence interval; EDSS = Expanded Disability Status Scale; IST = immunosuppressive therapy 
 
The adjudicated on-trial annualized relapse rate (ARR) ratio (95% CI) for eculizumab compared with 
placebo was 0.045 (0.013, 0.151), representing a 95.5% relative reduction in adjudicated On-trial ARR for 
patients treated with eculizumab compared with placebo (p<0.0001) (Table 13).  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

96 92 83 78 68 60 58 52 46 41 32 24 22 18 14 8 2 1

47 38 30 24 21 16 13 10 9 6 5 5 4 3 3 3 3 1

Eculizumab

Placebo

Number at Risk:

0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216

Time in Study Period (weeks)

0.0

0.2

0.4

0.6

0.8

1.0
Pr

op
or

tio
n 

Re
la

ps
e-

Fr
ee

Eculizumab
Placebo

0.979 (0.918, 0.995)         Hazard ratio (95% CI) (4,5): 0.058 (0.017, 0.197)
0.632 (0.468, 0.758)         Log rank p-value (3): <0.0001
48 Weeks (95% CI) (1,2):
Proportion Relapse-Free at

97.9% 96.4% 96.4%

63.2%

51.9%
45.4%



26 

Table 13:  Adjudicated On-trial Annualized Relapse Rate in Study ECU-NMO-301 – Full Analysis 
Set 

Variable Statistic Placebo  (N = 47) 
Eculizumab  

(N = 96) 
Total number of relapses Sum 21 3 
Total number of patient-years in study 
period n 52.41 171.32 

Adjusted adjudicated ARRa 
Rate 0.350 0.016 

95% CI 0.199, 0.616 0.005, 0.050 

Treatment effecta 

Rate ratio 
(eculizumab/placebo) … 0.045 

95% CI … 0.013, 0.151 

p-value … <0.0001 
a Based on a Poisson regression adjusted for randomization strata and historical ARR in 24 months 

prior to Screening. 
Abbreviations: ARR = annualized relapse rate; CI = confidence interval. 
 

Compared to placebo-treated patients, Soliris-treated patients had reduced annualized rates of 
hospitalizations (0.04 for Soliris versus 0.31 for placebo), of intravenous corticosteroid administrations to 
treat acute relapses (0.07 for Soliris versus 0.42 for placebo), and of plasma exchange treatments (0.02 for 
Soliris versus 0.19 for placebo). 
 
The distribution of changes from Baseline to End of Study on other secondary endpoints favored 
eculizumab treatment over placebo across all neurologic disability (EDSS score [p=0.0597] and mRS 
[nominal p=0.0154]), functional disability (HAI [nominal p=0.0002]) and quality of life (EQ-5D VAS 
[nominal p=0.0309] and EQ-5D Index [nominal p= 0.0077]) measures.  
 
An interim analysis of Study ECU-NMO-302 demonstrates a significant and clinically meaningful reduction 
in On-trial ARR (as determined by the Treating Physician) on eculizumab treatment, based on the median 
(min, max) change (-1.829 [-6.38, 1.63], p<0.0001) from historical ARR (24 months prior to screening in 
Study ECU-NMO-301).  
 
In Study ECU-NMO-302, physicians had the option to adjust background immunosuppressant therapies. In 
this setting, the most common change in immunosuppressant therapy was decreased immunosuppressant 
therapy dose, which occurred in 18.5% of patients. Further, 6.7% of patients stopped an existing IST. 
 
Soliris (eculizumab) has not been studied for the treatment of acute relapses in NMOSD patients. 
 
Paediatric population 
 
Paroxysmal Nocturnal Haemoglobinuria 
 
A total of 7 PNH paediatric patients, with a median weight of 57.2 kg (range of 48.6 to 69.8 kg) and aged 
from 11 to 17 years (median age : 15.6 years), received Soliris in study M07-005.  
 
Treatment with eculizumab at the proposed dosing regimen in the paediatric population was associated 
with a reduction of intravascular haemolysis as measured by serum LDH level. It also resulted in a marked 
decrease or elimination of blood transfusions, and a trend towards an overall improvement in general 
function. The efficacy of eculizumab treatment in paediatric PNH patients appears to be consistent with 
that observed in adult PNH patients enrolled in PNH pivotal Studies (C04-001 and C04-002) (Table 3 and 
14). 



27 

 
Table 14: Efficacy Outcomes in Paediatric PNH Study M07-005 

  P – Value 
 Mean (SD) Wilcoxon Signed 

Rank Paired t-test 

Change from baseline at 12 weeks of LDH 
Value (U/L) 

-771 (914) 0.0156 0.0336 

LDH AUC 
(U/L x Day) 

-60,634 
(72,916) 

0.0156 0.0350 

Change from baseline at 12 weeks in 
Plasma Free Haemoglobin (mg/dL) -10.3 (21.13) 0.2188 0.1232 

Change from baseline Type III RBC clone 
size (Percent of aberrant cells) 1.80 (358.1)   

Change from baseline at 12 weeks of 
PedsQLTM4.0 Generic Core scale (patients) 10.5 (6.66) 0.1250 0.0256 

Change from baseline at 12 weeks of 
PedsQLTM4.0 Generic Core scale (parents) 11.3 (8.5) 0.2500 0.0737 

Change from baseline at 12 weeks of 
PedsQLTM Multidimensional Fatigue 
(patients) 

0.8 (21.39) 0.6250 0.4687 

Change from baseline at 12 weeks of 
PedsQLTM Multidimensional Fatigue 
(parents) 

5.5 (0.71) 0.5000 0.0289 

 
Atypical Haemolytic Uremic Syndrome 
 
A total of 15 paediatric patients (aged 2 months to 12 years) received Soliris in aHUS Study C09-001r. 
Forty seven percent of patients had an identified complement regulatory factor mutation or auto-antibody. 
The median time from aHUS diagnosis to first dose of Soliris was 14 months (range <1, 110 months). The 
median time from current thrombotic microangiopathy manifestation to first dose of Soliris was 1 month 
(range <1 to 16 months). The median duration of Soliris therapy was 16 weeks (range 4 to 70 weeks) for 
children < 2 years of age (n=5) and 31 weeks (range 19 to 63 weeks) for children 2 to <12 years of age 
(n=10).  
Overall, the efficacy results for these paediatric patients appeared consistent with what was observed in 
patients enrolled in aHUS pivotal Studies C08-002 and C08-003 (Table 6). No paediatric patient required 
new dialysis during treatment with Soliris. 
 



28 

Table 15: Efficacy Results in Paediatric Patients Enrolled in aHUS C09-001r 

Efficacy Parameter <2 years (n=5) 
2 to <12 years 

(n=10) 
<12 years 

(n=15) 
Patients with platelet count 
normalization, n (%)  

4 (80) 10 (100) 14 (93) 

Complete TMA response, n (%)  2 (40) 5 (50) 7 (50) 

Daily TMA intervention rate, 
median (range) 
    Before eculizumab 
    On eculizumab treatment 

 
 

1 (0, 2) 
<1 (0, <1) 

 
 

<1 (0.07, 1.46) 
0 (0, <1) 

 
 

<1 (0, 2) 
0 (0, <1) 

Patients with eGFR improvement 
≥15 mL/min/1.73 m2, n (%)  

2 (40) 6 (60) 8 (53) 

 
In paediatric patients with shorter duration of current severe clinical thrombotic microangiopathy (TMA) 
manifestation prior to eculizumab, there was TMA control and improvement of renal function with 
eculizumab treatment (Table 15). 
In paediatric patients with longer duration of current severe clinical TMA manifestation prior to 
eculizumab, there was TMA control with eculizumab treatment.  However, renal function was not 
changed due to prior irreversible kidney damage (Table 16). 
 
Table 16: Efficacy Outcomes in Paediatric Patients in Study C09-001r according to duration of 
current severe clinical thrombotic microangiopathy (TMA) manifestation 

 Duration of current severe 
clinical TMA manifestation 

 < 2 months 
N=10 (%) 

>2 months 
N=5 (%) 

Platelet count normalization 9 (90) 5 (100) 
TMA event-free status 8 (80) 3 (60) 
Complete TMA response 7 (70) 0 
eGFR improvement ≥ 15 mL/min/1.73m2 7 (70) 0* 

*One patient achieved eGFR improvement after renal transplant 
 
A total of 22 paediatric and adolescents patients (aged 5 months to 17 years) received Soliris in 
aHUS Study C10-003. 

In Study C10-003, patients who enrolled in the study were required to have a platelet count < lower limit 
of normal range (LLN), evidence of haemolysis such as an elevation in serum LDH above the upper limits 
of normal and serum creatinine level ≥97 percentile for age without the need for chronic dialysis.  The 
median patient age was 6.5 years (range: 5 months to 17 years). Patients enrolled in aHUS C10-003   had 
an ADAMTS-13 level above 5%. Fifty percent of patients had an identified complement regulatory factor 
mutation or auto-antibody. A total of 10 patients received PE/PI prior to eculizumab. Table 17 summarizes 
the key baseline clinical and disease-related characteristics of patients enrolled in aHUS Study C10-003. 



29 

Table 17:  Baseline Characteristics of Paediatric and Adolescents Patients Enrolled in aHUS Study 
C10-003    

Parameter 
1 month to <12 years 

(N = 18)  
 

 All Patients 
(N = 22)  

 

Time from aHUS diagnosis until first study dose 
(months) median (min, max  ) 0.51 (0.03, 58) 0.56 (0.03,191) 

Time from current clinical TMA manifestation 
until first study dose  (months), median ( min, 
max) 

0.23 (0.03, 4) 0.20 (0.03, 4) 

Baseline platelet count (x 109/L), median ( min, 
max) 110 (19, 146) 91 (19,146) 

Baseline LDH (U/L) median (min, max ) 1510 (282, 7164) 1244 (282, 7164) 

Baseline  eGFR (mL/min/1.73 m2 ), median (min, 
max) 22 (10, 105) 22 (10, 105) 

 

Patients in aHUS C10-003 received Soliris for a minimum of 26 weeks. After completion of the initial 26-
week treatment period, most patients elected to continue on chronic dosing. Reduction in terminal 
complement activity was observed in all patients after commencement of Soliris. Soliris reduced signs of 
complement-mediated TMA activity, as shown by an increase in mean platelet counts from baseline to 26 
weeks. The mean (±SD) platelet count increased from 88 ± 42 x109/L at baseline to 281 ± 123 x109/L by 
one week; this effect was maintained through 26 weeks (mean platelet count (±SD) at week 26: 293 ± 106 
x109/L). Renal function, as measured by eGFR, was improved during Soliris therapy. Nine of the 11 
patients who required dialysis at baseline no longer required dialysis after Study Day 15 of eculizumab 
treatment. Responses were similar across all ages from 5 months to 17 years of age. In aHUS C10-003, 
responses to Soliris were similar in patients with and without identified mutations in genes encoding 
complement regulatory factor proteins or auto-antibodies to factor H.   

Table 18 summarizes the efficacy results for aHUS C10-003. 

 

 

 

 

 

 

 

 

 

 

 



30 

Table 18:  Efficacy Outcomes in Prospective aHUS Study C10-003    

Efficacy Parameter 
1 month to <12 years 

(N = 18) 
At 26-weeks 

All Patients  
(N = 22)   

At 26-weeks 

Complete Hematologic Normalization, n (%)  
Median Duration of complete hematologic 
normalization, weeks (range) 1 

14 (78) 
35 (13, 78) 

18 (82) 
 35 (13, 78) 

Complete TMA response, n (%) 

Median Duration of complete TMA response, 
weeks (range)1 

11 (61) 

40 (13, 78) 

14 (64) 

37 (13, 78) 

TMA Event-Free Status, n (%) 
      95% CI  

17 (94) 
NA 

21 (96) 
77; 99 

Daily TMA Intervention rate, median (range) 
     Before eculizumab treatment, median    
     On eculizumab treatment, median 

NA 
NA 

0.4 (0, 1.7) 
0 (0, 1.01) 

eGFR improvement ≥15 mL/min/ 1.73•m2, n (%) 16 (89) 19 (86) 

Change in eGFR ( ≥15 mL/min/1.73•m2) at 26 
weeks, median (range) 64 (0,146) 58 (0, 146) 

CKD improvement by ≥1 stage, n (%) 14/16 (88) 17/20 (85) 

PE/PI Event-Free Status, n (%) 
New Dialysis Event-Free Status, n (%) 
      95% CI 

16 (89) 
18 (100) 

NA 

20 (91) 
22 (100) 
85;100 

1 Through data cut-off (October 12, 2012), with median duration of Soliris therapy of 44 weeks (range: 1 dose to 88 
weeks). 

 
Longer term treatment with Soliris (median 55 weeks ranging from 1day to 107 weeks) was associated 
with an increased rate of clinically meaningful improvements in paediatric and adolescent patients with 
aHUS. When Soliris treatment was continued for more than 26 weeks, one additional patient (68% of 
patients in total) achieved Complete TMA Response and two additional patients (91% of patients in total) 
achieved hematologic normalization. At the last evaluation, 19 of 22 patients (86%) achieved eGFR 
improvement of  ≥ 15 mL/min/1.73 m2 from baseline. No patient required new dialysis with Soliris. 
 
Refractory Generalized Myasthenia Gravis 
Soliris has not been evaluated in paediatric patients with refractory gMG. 
The European Medicines Agency has deferred the obligation to submit the results of studies with Soliris in 
one or more subsets of the paediatric population in the treatment of refractory gMG (see section 4.2 for 
information on paediatric use). 
 
Neuromyelitis Optica Spectrum Disorder 
Soliris has not been evaluated in paediatric patients with NMOSD. 
The European Medicines Agency has deferred the obligation to submit the results of studies with Soliris in 
one or more subsets of the paediatric population in the treatment of NMOSD (see section 4.2 for 
information on paediatric use). 
 
 



31 

5.2 Pharmacokinetic properties  
 
Pharmacokinetics and Drug Metabolism 
 
Biotransformation 
Human antibodies undergo endocytotic digestion in the cells of the reticuloendothelial system. 
Eculizumab contains only naturally occurring amino acids and has no known active metabolites. Human 
antibodies are predominately catabolized by lysosomal enzymes to small peptides and amino acids. 
 
Elimination 
No specific studies have been performed to evaluate the hepatic, renal, lung, or gastrointestinal routes of 
excretion/elimination for Soliris. In normal kidneys, antibodies are not excreted and are excluded from 
filtration by their size. 
 
Pharmacokinetic Parameters 
In 40 patients with PNH, a 1-compartmental model was used to estimate pharmacokinetic parameters after 
multiple doses. Mean clearance was 0.31 ± 0.12 mL/hr/kg, mean volume of distribution was 110.3 ± 
17.9 mL/kg, and mean elimination half-life was 11.3 ± 3.4 days. The steady state is achieved by 4 weeks 
using the PNH adult dosing regimen. 
 
In PNH patients, pharmacodynamic activity correlates directly with eculizumab serum concentrations and 
maintenance of trough levels above ≥ 35 microgram/mL results in essentially complete blockade of 
haemolytic activity in the majority of PNH patients. 
 
A second population PK analysis with a standard 1 compartmental model was conducted on the multiple 
dose PK data from 37 aHUS patients receiving the recommended Soliris regimen in studies C08-002A/B 
and C08-003A/B. In this model, the clearance of Soliris for a typical aHUS patient weighing 70 kg was 
0.0139 L/hr and the volume of distribution was 5.6 L. The elimination half-life was 297 h (approximately 
12.4 days).  
 
The second population PK model was applied to the multiple dose PK data from 22 paediatric aHUS 
patients receiving the recommended Soliris regimen in aHUS C10-003. The clearance and volume of 
distribution of Soliris are weight dependent, which forms the basis for a weight categorical based dose 
regimen in paediatric patients (see section 4.2). Clearance values of Soliris in paediatric aHUS patients 
were 10.4, 5.3, and 2.2 mL/hr with body weight of 70, 30, and 10 kg, respectively; and the corresponding 
volume of distribution values were 5.23, 2.76, and 1.21 L, respectively. The corresponding elimination 
half-life remained almost unchanged within a range of 349 to 378 h (approximately 14.5 to 15.8 days). 
 
The clearance and half-life of eculizumab were also evaluated during plasma exchange interventions.  
Plasma exchange resulted in an approximately 50% decline in eculizumab concentrations following a 
1 hour intervention and the elimination half-life of eculizumab was reduced to 1.3 hours. Supplemental 
dosing is recommended when Soliris is administered to aHUS patients receiving plasma infusion or 
exchange (see section 4.2). 
 
All aHUS patients treated with Soliris when administered as recommended demonstrated rapid and 
sustained reduction in terminal complement activity. In aHUS patients, pharmacodynamic activity 
correlates directly with eculizumab serum concentrations and maintenance of trough levels of 
approximately 50-100 microgram/ml results in essentially complete blockade of terminal complement 
activity in all aHUS patients.  
 
PK parameters are consistent across PNH, aHUS, refractory gMG and NMOSD patient populations.  



32 

Pharmacodynamic activity measured by free C5 concentrations of <0.5 ug/mL, is correlated with 
essentially complete blockade of terminal complement activity in PNH, aHUS, refractory gMG and 
NMOSD patients.  
 
Special Populations 
 
Dedicated studies have not been conducted to evaluate the pharmacokinetics of Soliris in special patient 
populations identified by gender, race, age (geriatric), or the presence of renal or hepatic impairment.  
Population PK analysis on data collected across studies in PNH, aHUS, gMG and NMOSD patients 
showed that gender, race, age (geriatric), or the presence of renal or hepatic impairment.function do not 
influence the PK of eculizumab. Body weight was a significant covariate resulting in a lower eculizumab 
clearance in pediatric patients requiring body weight based dosing in pediatric patients.  
 
 
Paediatric population 

The pharmacokinetics of eculizumab was evaluated in Study M07-005 in PNH paediatric patients (aged 
from 11 to less than 18 years) and in Studies C08-002, C08-003, C09-001r and C10-003 in aHUS 
pediatric patients (aged 2 months to less than 18 years) with body-weight based dose regimen.  

Weight was a significant covariate resulting in a lower eculizumab clearance 0.0105 L/h in the adolescent 
PNH patients. Dosing for paediatric patients <40 kg is based on paediatric patients with aHUS. 

 
5.3 Preclinical safety data 
 
The specificity of eculizumab for C5 in human serum was evaluated in two in vitro studies.   
 
The tissue cross-reactivity of eculizumab was evaluated by assessing binding to a panel of 38 human 
tissues. C5 expression in the human tissue panel examined in this study is consistent with published 
reports of C5 expression, as C5 has been reported in smooth muscle, striated muscle, and renal proximal 
tubular epithelium. No unexpected tissue cross-reactivity was observed. 
 
Animal reproduction studies have not been conducted with eculizumab due to lack of pharmacologic 
activity in non-human species.  
 
In a 26 week toxicity study performed in mice with a surrogate antibody directed against murine C5, 
treatment did not affect any of the toxicity parameters examined. Haemolytic activity during the course of 
the study was effectively blocked in both female and male mice.  
 
No clear treatment-related effects or adverse effects were observed in reproductive toxicology studies in 
mice with a surrogate terminal complement inhibitory antibody, which was utilized to assess the 
reproductive safety of C5 blockade. These studies included assessment of fertility and early embryonic 
development, developmental toxicity, and pre and post-natal development. 
 
When maternal exposure to the antibody occurred during organogenesis, two cases of retinal dysplasia and 
one case of umbilical hernia were observed among 230 offspring born to mothers exposed to the higher 
antibody dose (approximately 4 times the maximum recommended human Soliris dose, based on a body 
weight comparison); however, the exposure did not increase foetal loss or neonatal death. 
 
No animal studies have been conducted to evaluate the genotoxic and carcinogenic potential of 
eculizumab. 
 
 
 



33 

6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium phosphate, monobasic  
Sodium phosphate, dibasic  
Sodium chloride 
Polysorbate 80 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
30 months. 
 
After dilution, the medicinal product should be used immediately. However, chemical and physical 
stability has been demonstrated for 24 hours at 2°C – 8°C.  
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze.  
Store in the original package in order to protect from light. 
Soliris vials in the original package may be removed from refrigerated storage for only one single period 
of up to 3 days. At the end of this period the product can be put back in the refrigerator. 
For storage conditions after dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
30 ml of concentrate in a vial (Type I glass) with a stopper (butyl, siliconised), and a seal (aluminium) 
with flip-off cap (polypropylene). 
 
Pack size of one vial. 
 
6.6 Special precautions for disposal and other handling 
 
Prior to administration, the Soliris solution should be visually inspected for particulate matter and 
discolouration.  
 
 
Instructions:  
Reconstitution and dilution should be performed in accordance with good practices rules, particularly for 
the respect of asepsis. 
 
Withdraw the total amount of Soliris from the vial(s) using a sterile syringe. 
 
Transfer the recommended dose to an infusion bag. 
 



34 

Dilute Soliris to a final concentration of 5 mg/ml by addition to the infusion bag using sodium chloride 
9 mg/ml (0.9%) solution for injection, sodium chloride 4.5 mg/ml (0.45%) solution for injection, or 5% 
dextrose in water, as the diluent. 
The final volume of a 5 mg/ml diluted solution is 60 ml for 300 mg doses, 120 ml for 600 mg doses, 
180 ml for 900 mg doses and 240 ml for 1,200 mg doses. The solution should be clear and colourless. 
 
Gently agitate the infusion bag containing the diluted solution to ensure thorough mixing of the product 
and diluent.  
 
The diluted solution should be allowed to warm to room temperature prior to administration by exposure 
to ambient air.   
 
Discard any unused portion left in a vial, as the product contains no preservatives. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Alexion Europe SAS 
103-105 rue Anatole France  
92300 Levallois-Perret  
FRANCE 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/393/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 20 June 2007 
Date of latest renewal : 18 June 2012 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Date:    
 
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/


35 

 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND 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 
 
 

 



36 

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

 
Name and address of the manufacturers of the biological active substance 
 
Lonza Biologics, plc. 
228 Bath Road 
Slough 
Berkshire SL1 4DX 
United Kingdom 
 
Alexion Rhode Island Manufacturing Facility (ARIMF) 
100 Technology Way 
Smithfield, Rhode Island 02917 
U.S.A. 
 
Lonza Biologics Tuas Pte Ltd. 
35 Tuas South Avenue 6  
Singapore 637377 
 
Lonza Biologics Porriño, S.L. 
C/ La Relba, s/n. 
Porriño  
Pontevedra 36400 
Spain 
 
 
Name and address of the manufacturers responsible for batch release 
 
Almac Pharma Services 
22 Seagoe Industrial Estate 
Craigavon BT63 5QD 
United Kingdom 
 
Patheon Italia S.p.A 
Viale G. B. Stucchi, 110 
20900 Monza (MB) 
Italy 
 
Alexion Pharma International  
Operations Unlimited Company 
College Business and Technology Park 
Blanchardstown 
Dublin 15 
Ireland 
 
 
The printed package leaflet of the medicinal product must state the name and address of the manufacturer 
responsible for the release of the concerned batch. 
 
 
 
 



37 

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 
The requirements for submission of periodic safety update reports 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. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 
USE OF THE MEDICINAL PRODUCT 
 
Risk Management Plan (RMP) 
The 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. 

 
Additional risk minimisation measures 
 
The MAH shall agree the details of a controlled drug distribution system and educational material 
including a patient safety card with each National Competent Authority and must implement such 
programmes nationally to ensure that: 
 

1. All healthcare practitioners who may prescribe eculizumab receive the appropriate educational 
material. 

 
2. All patients being treated with eculizumab receive a patient safety card. 

 
3. Drug distribution will only be possible after written confirmation that the patient received or will 

receive meningococcal vaccination and/or antibiotic prophylaxis. 
 
4. Vaccination reminders are sent to the prescribers. 

 
The educational material should be agreed with the National Competent Authority and should contain the 
following: 

• Summary of product characteristics 
• Physician’s guides to prescribing 
• Package leaflet 
• Patient’s/parent’s information brochures 
• Patient safety card 



38 

 
The physician’s guides to prescribing should be indication specific and contain the following key 
messages: 

• Treatment with eculizumab increases the risk of severe infection and sepsis, especially of Neisseria 
meningitidis and other Neisseria species, including disseminated gonorrhoeae. 

• All patients must be monitored for signs of meningococcal infection. 
• The need for patients to be vaccinated against Neisseria meningitidis two weeks prior to receiving 

eculizumab and/or to receive antibiotic prophylaxis. 
• The requirement to vaccinate children against pneumococcus and Haemophilus influenzae before 

eculizumab treatment. 
• There is an important risk of Aspergillus infection in patients treated with eculizumab. The 

healthcare professionals should be advised to look for risk factors and signs and symptoms of 
Aspergillus infection. Practical advice should be included to mitigate the risk. 

• The risk of infusion reactions including anaphylaxis and advice on post-infusion monitoring. 
• The risk of developing antibodies to eculizumab. 
• Risk of serious haemolysis following eculizumab discontinuation and postponement of 

administration, its criteria, the required post-treatment monitoring and its proposed management 
(PNH only). 

• Risk of severe thrombotic microangiopathic complications following eculizumab discontinuation 
and postponement of administration, its signs, symptoms, monitoring and management (aHUS 
only).  

• Risk of substantial disease exacerbation or relapse following eculizumab discontinuation (refractory 
gMG) 

• The need to explain to and ensure understanding of by patients/carers: 
o the risks of treatment with eculizumab 
o the signs and symptoms of sepsis/severe infection and what action to take 
o the patient’s/carer’s guides and their contents 
o the need to carry the patient safety card and to tell any healthcare practitioner that he/she is 

receiving treatment with eculizumab 
o the requirement for  vaccinations/antibiotic prophylaxis 
o the enrolment in the registries 

• Details of the PNH and aHUS registries and how to enter patients. 
 
The patient’s/parent’s guides should be indication specific and contain the following key messages: 
• Treatment with eculizumab increases the risk of severe infection, especially Neisseria meningitidis 

and other Neisseria species, including disseminated gonorrhoeae. 
• Signs and symptoms of severe infection and the need to obtain urgent medical care. 
• The patient safety card and the need to carry it on their person and tell any treating healthcare 

professional that they are being treated with eculizumab. 
• The importance of meningococcal vaccination prior to treatment with eculizumab and/or to 

receive antibiotic prophylaxis. 
• The need for children to be vaccinated against pneumococcus and Haemophilus influenzae before 

eculizumab treatment. 
• The risk of infusion reactions with eculizumab, including anaphylaxis, and the need for clinical 

monitoring post-infusion. 
• Risk of severe thrombotic microangiopathic complications (in aHUS) following 

discontinuation/postponement of eculizumab administrations, their signs and symptoms and the 
recommendation to consult the prescriber before discontinuing/postponing eculizumab 
administrations. 

• Risk of serious haemolysis (in PNH) following discontinuation/postponement of eculizumab 
administrations, their signs and symptoms and the recommendation to consult the prescriber before 
discontinuing/postponing eculizumab administrations. 



39 

• Risk of substantial disease exacerbation or relapse (in refractory gMG) following 
discontinuation/postponement of eculizumab administrations and recommendation to consult the 
prescriber before discontinuing/postponing eculizumab administrations. 

• Enrolment in the PNH and aHUS registries. 
 

The patient safety card should contain: 
• Signs and symptoms of infection and sepsis. 
• Warning to seek immediate medical care if above are present. 
• Statement that the patient is receiving eculizumab. 
• Contact details where a health care practitioner can receive further information. 

 

The MAH shall send annually to prescribers or pharmacists who prescribe/dispense eculizumab, a 
reminder in order that prescriber/pharmacist checks if a (re)-vaccination against Neisseria meningitidis is 
needed for his/her patients on eculizumab.  



40 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

  



41 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



42 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton Label 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Soliris 300 mg concentrate for solution for infusion 
Eculizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial of 30 ml contains 300 mg of eculizumab (10mg/ml) 
 
Eculizumab is a humanised monoclonal IgG2/4 k antibody produced in NS0 cell line by recombinant DNA 
technology. 
 
After dilution, the final concentration of the solution to be infused is 5 mg/ml.  
 
 
3. LIST OF EXCIPIENTS 
 
Sodium as chloride, phosphate dibasic, phosphate monobasic, polysorbate 80 and water for injections. 
 
See package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
1 vial of 30 ml (10 mg/ml) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. 
Must be diluted before use. 
Read the package leaflet before use. 
 
 
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 



43 

 
EXP 
After dilution, the medicinal product should be used within 24 hours. 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator (2°C – 8°C). 
Do not freeze.  
Store in the original package 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 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Marketing Authorisation Holder:  
Alexion Europe SAS 
103-105 rue Anatole France 
92300 Levallois-Perret 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/07/393/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 



44 

2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: {number} [product code] 
SN: {number} [serial number] 
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product] 
  



45 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
 
Single use Type I glass vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Soliris 300 mg concentrate for solution for infusion 
Eculizumab 
For intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
To be diluted before use. 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
30 ml (10 mg/ml) 
 
 
6. OTHER 
 
 
 
 
 
 
 
 
 
 
 
 
  



46 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
  



47 

Package leaflet: Information for the user 
 

Soliris 300 mg concentrate for solution for infusion 
Eculizumab 

 
Read all of this leaflet carefully before you start using 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, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even 

if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet:  
1. What Soliris is and what it is used for 
2. What you need to know before you use Soliris 
3. How to use Soliris 
4. Possible side effects 
5. How to store Soliris 
6. Contents of the pack and other information 
 
 
1. What Soliris is and what it is used for 

 
What is Soliris 
Soliris contains the active substance eculizumab and it belongs to a class of medicines called monoclonal 
antibodies. Eculizumab binds to and inhibits a specific protein in the body that causes inflammation and so 
prevents your body’s systems from attacking and destroying vulnerable blood cells, kidneys, muscles or 
eye nerves and spinal cord. 
 
What is Soliris used for 
Paroxysmal Nocturnal Haemoglobinuria 
Soliris is used to treat adults and children patients with a certain type of disease affecting the blood system 
called Paroxysmal Nocturnal Haemoglobinuria (PNH). In patients with PNH, their red blood cells can be 
destroyed which can lead to low blood counts (anaemia), tiredness, difficulty in functioning, pain, dark 
urine, shortness of breath, and blood clots. Eculizumab can block the body’s inflammatory response, and 
its ability to attack and destroy its own vulnerable PNH blood cells.  
 
Atypical Haemolytic Uremic Syndrome 
Soliris is also used to treat adults and children patients with a certain type of disease affecting the blood 
system and kidney called atypical Haemolytic Uremic Syndrome (aHUS). In patients with aHUS, their 
kidney and blood cells, including platelets, can be inflamed which can lead to low blood counts 
(thrombocytopenia and anaemia), reduced or lost kidney function, blood clots, tiredness and difficulty in 
functioning. Eculizumab can block the body’s inflammatory response, and its ability to attack and destroy 
its own vulnerable blood and kidney cells.  
 
Refractory Generalized Myasthenia Gravis 
Soliris is also used to treat adult patients with a certain type of disease affecting the muscles and called 
generalized Myasthenia Gravis (gMG). In patients with gMG, their muscles can be attacked and damaged 
by the immune system which can lead to profound muscle weakness, impaired mobility, shortness of 
breath, extreme fatigue, risk for aspiration, and markedly impaired activities of daily living. Soliris can 



48 

block the body’s inflammatory response, and its ability to attack and destroy its own muscles to improve 
muscle contraction, thereby reducing symptoms of the disease and impact of the disease on the activities 
of daily living. Soliris is specifically indicated for patients who remain symptomatic despite treatment 
with other existing MG therapies. 
 
Neuromyelitis Optica Spectrum Disorders 
Soliris is also used to treat adult patients with a certain type of disease that predominantly affects the eye 
nerves and the spinal cord called Neuromyelitis Optica Spectrum Disorder (NMOSD). In patients with 
NMOSD, their eye nerve and spinal cord are attacked and damaged by the immune system which can lead 
to blindness in one or both eyes, weakness or paralysis in the legs or arms, painful spasms, loss of 
sensation, and markedly impaired activities of daily living. Soliris can block the body’s inflammatory 
response, and its ability to attack and destroy its own eye nerves and spinal cord, thereby reducing 
symptoms of the disease and impact of the disease on the activities of daily living. 
 
 
2. What you need to know before you use Soliris 

 
Do not use Soliris 
 
- If you are allergic to eculizumab, proteins derived from mouse products, other monoclonal 

antibodies, or any of the other ingredients of this medicine (listed in section 6). 
- If you have not been vaccinated against meningococcal infection unless you take antibiotics to 

reduce the risk of infection until 2 weeks after you have been vaccinated . 
- If you have a meningococcal infection. 
 
Warnings and precautions 
 
Meningococcal and other Neisseria infections alert 
Soliris treatment may reduce your natural resistance to infections, especially against certain organisms that 
cause meningococcal infection (severe infection of the linings of the brain and sepsis) and other Neisseria 
infections including disseminated gonorrhea. 
 
Consult your doctor before you take Soliris to be sure that you receive vaccination against Neisseria 
meningitidis, an organism that causes meningococcal infection, at least 2 weeks before beginning therapy, 
or that you take antibiotics to reduce the risk of infection until 2 weeks after you have been vaccinated. 
Ensure that your current meningococcal vaccination is up to date. You should also be aware that 
vaccination may not prevent this type of infection. In accordance with national recommendations, your 
doctor might consider that you need supplementary measures to prevent infection. 
 
If you are at risk of gonorrhoea, ask your doctor or pharmacist for advice before using this medicine. 
 
Meningococcal infection symptoms 
Because of the importance of rapidly identifying and treating certain types of infection in patients who 
receive Soliris, you will be provided a card to carry with you, listing specific trigger symptoms. This card 
is named: “Patient Safety Card”. 
 
If you experience any of the following symptoms, you should immediately inform your doctor:    
- headache with nausea or vomiting 
- headache with a stiff neck or back 
- fever 
- rash  
- confusion  
- severe muscle aches combined with flu-like symptoms 



49 

- sensitivity to light 
 
Treatment for meningococcal infection while travelling 
If you are travelling in a remote region where you are unable to contact your doctor or in which you find 
yourself temporarily unable to receive medical treatment, your doctor can make arrangements to issue, as 
a preventive measure, a prescription for an antibiotic to counter Neisseria meningitidis that you keep with 
you. If you experience any of the symptoms amongst those cited above, you should take the antibiotics as 
prescribed. You should bear in mind that you should see a doctor as soon as possible, even if you feel 
better after having taken the antibiotics. 
 
Infections 
Before starting Soliris, inform your doctor if you have any infections. 
 
Allergic reactions 
Soliris contains a protein and proteins can cause allergic reactions in some people.  
 
Children and adolescents 
Patients less than 18 years of age must be vaccinated against Haemophilus influenzae and pneumococcal 
infections 
 
Older people 
There are no special precautions needed for the treatment of patients aged from 65 years and over. 
 
Other medicines and Soliris 
Tell your doctor or pharmacist if you are using or have recently used or might use any other medicines. 
 
Pregnancy, breast-feeding, and fertility 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your 
doctor or pharmacist for advice before using this medicine. 
 
Women of childbearing potential 
The use of effective contraception during treatment and up to 5 months after treatment should be 
considered in women who are able to get pregnant.  
 
Pregnancy/ Breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your 
doctor or pharmacist for advice before using this medicine. 

Driving and using machines 
Soliris has no or negligible influence on the ability to drive and use machines.  
 
Soliris contains sodium 
This medicinal product contains 115 mg sodium per vial. You should take into consideration if you are on 
a controlled sodium diet. 
 
3. How to use Soliris 
 
At least 2 weeks before you start treatment with Soliris, your doctor will administer a vaccine against 
meningococcal infection if it was not previously administered or if your vaccination is outdated. If your 
child is below the age of vaccination or if you are not vaccinated at least 2 weeks before you start 
treatment with Soliris, your doctor will prescribe antibiotics to reduce the risk of infection until 2 weeks 
after you have been vaccinated. 



50 

Your doctor will administer a vaccine to your child aged less than 18 years against Haemophilus 
influenzae and pneumococcal infections according to the national vaccination recommendations for each 
age group. 
 
Instructions for proper use 
The treatment will be given by your doctor or other health care provider by infusing a dilution of the 
Soliris vial from a drip bag through a tube directly into one of your veins. It is recommended that the 
beginning of your treatments, called the initial phase, will extend over 4 weeks, followed by a 
maintenance phase. 
 
If you use this medicine to treat PNH 
For adults: 
• Initial Phase: 
 Every week for the first four weeks,  your doctor will administer an intravenous infusion of diluted 

Soliris. Each infusion will consist of a dose of 600 mg (2 vials of 30 ml) and will take 25 – 45 minutes 
(35 minutes ± 10 minutes). 

 
• Maintenance Phase: 

• In the fifth week, your doctor will administer an intravenous infusion of diluted Soliris at a dose 
of 900 mg (3 vials of 30 ml) over a 25 – 45 minute (35 minutes ± 10 minutes) period. 

• After the fifth week, your doctor will administer 900 mg of diluted Soliris every two weeks as a 
long-term treatment.  

 
If you use this medicine to treat aHUS, refractory gMG or NMOSD 
For adults: 
• Initial Phase: 

Every week for the first four weeks,  your doctor will administer an intravenous infusion of diluted 
Soliris. Each infusion will consist of a dose of 900 mg (3 vials of 30 ml) and will take 25 – 45 minutes 
(35 minutes ± 10 minutes). 
 

• Maintenance Phase: 
• In the fifth week, your doctor will administer an intravenous infusion of diluted Soliris at a dose 

of 1,200 mg (4 vials of 30 ml) over a 25 – 45 minute (35 minutes ± 10 minutes) period. 
• After the fifth week, your doctor will administer 1,200 mg of diluted Soliris every two weeks as 

a long-term treatment.  
 
Children and adolescents with PNH or aHUS and who are 40 kg weight and over are treated with the adult 
dosing. 
 
Children and adolescents with PNH or aHUS and who are under 40 kg weight require a lower dose based 
on how much they weigh. Your doctor will calculate this. 
 
For children and adolescents with PNH and aHUS aged less than 18 years: 

Body Weight Initial Phase Maintenance Phase 
30 to <40 kg 600 mg weekly x 2 900 mg at week 3; then 900 mg every 2  weeks 
20 to <30 kg 600 mg weekly x 2 600 mg at week 3; then 600 mg every 2 weeks 
10 to <20 kg 600 mg weekly x 1 300 mg at week 2; then 300 mg every 2 weeks 
5 to <10 kg 300 mg weekly x 1 300 mg at week 2; then 300 mg every 3 weeks 

 
Subjects who undergo plasma exchange may receive additional doses of Soliris. 
 



51 

Following each infusion, you will be monitored for about one hour. Your doctor’s instructions should be 
carefully observed. 
 
If you receive more Soliris than you should  
If you suspect that you have been accidentally administered a higher dose of Soliris than prescribed, 
please contact your doctor for advice. 
 
If you forget an appointment to receive Soliris 
If you forget an appointment, please contact your doctor immediately for advice and see section below “If 
you stop using Soliris”. 
 
If you stop using Soliris for PNH 
Interrupting or ending treatment with Soliris may cause your PNH symptoms to come back more severely 
soon. Your doctor will discuss the possible side effects with you and explain the risks. Your doctor will 
want to monitor you closely for at least 8 weeks. 
 
The risks of stopping Soliris include an increase in the destruction of your red blood cells, which may 
cause: 
- A significant fall in your red blood cell counts (anaemia),  
- Confusion or change in how alert you are, 
- Chest pain, or angina, 
- An increase in your serum creatinine level (problems with your kidneys), or 
- Thrombosis (blood clotting).    
If you have any of these symptoms, contact your doctor.    
 
If you stop using Soliris for aHUS  
Interrupting or ending treatment with Soliris may cause your aHUS symptoms to come back. Your doctor 
will discuss the possible side effects with you and explain the risks. Your doctor will want to monitor you 
closely. 
 
The risks of stopping Soliris include an increase in the inflammation of your platelets, which may cause: 
- A significant fall in your platelets (thrombocytopenia), 
- A significant rise in destruction of your red blood cells, 
- Decreased urination (problems with your kidneys), 
- An increase in your serum creatinine level (problems with your kidneys),  
- Confusion or change in how alert you are, 
- Chest pain, or angina, 
- Shortness of breath, or 
- Thrombosis (blood clotting).    
 
If you have any of these symptoms, contact your doctor.    
 
If you stop using Soliris for refractory gMG  
Interrupting or stopping treatment with Soliris may cause your gMG symptoms to come back. Please 
speak to your doctor before stopping Soliris. Your doctor will discuss the possible side effects and risks 
with you. Your doctor will also want to monitor you closely. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist or nurse. 
 
If you stop using Soliris for NMOSD 
Interrupting or stopping treatment with Soliris may cause your NMOSD to worsen and relapse to happen. 
Please speak to your doctor before stopping Soliris. Your doctor will discuss the possible side effects and 
risks with you. Your doctor will also want to monitor you closely. 



52 

 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Your doctor 
will discuss the possible side effects with you and explain the risks and benefits of Soliris with you prior to 
treatment. 
The most serious side effect was meningococcal sepsis. 
If you experience any of the meningococcal infection symptoms (see section 2 Meningococcal and other 
Neisseria infections alert), you should immediately inform your doctor. 
 
If you are not sure what the side effects below are, ask your doctor to explain them to you.  
 
Very common: may affect more than 1 in 10 people: headache. 
 
Common: may affect up to 1 in 10 people: 
• infection of the lung (pneumonia), common cold (nasopharyngitis), infection of the urinary system 

(urinary tract infection),  
• low white blood cell count (leukopenia), reduction in red blood cells which can make the skin pale and 

cause weakness or breathlessness 
• inability to sleep 
• dizziness, taste disorders (dysgeusia), high blood pressure 
• upper respiratory tract infection, cough, throat pain (oropharyngeal pain), bronchitis, cold sores (herpes 

simplex) 
• diarrhea, vomiting, nausea, abdominal pain, rash, hair loss (alopecia), itchy skin (pruritus) 
• pain in thejoints (arms and legs)  
• fever (pyrexia), feeling tired (fatigue), influenza like illness 
 
Uncommon: may affect up to 1 in 100 people: 
• severe infection (meningococcal infection), sepsis, septic shock, viral infection, , lower respiratory tract 

infection, stomach flu (gastrointestinal infection), cystitis 
• infection, fungal infection, collection of pus (abscess), type of infection of the skin (cellulitis), 

influenza, sinusitis, tooth infection (abscess)  
• relatively few platelets in blood (thrombocytopenia), low level of lymphocytes a specific type of white 

blood cells (lymphopenia), feeling your heartbeat  
• serious allergic reaction which causes difficulty in breathing or dizziness (anaphylactic reaction), 

hypersensitivity 
• loss of appetite 
• depression, anxiety, mood swings  
• tingling in part of the body (paresthesia), shaking 
• vision blurred 
• ringing in the ears, vertigo 
• sudden and rapid development of extremely high blood pressure, low blood pressure, hot flush, vein 

disorder  
• dyspnoea (difficulty breathing), nose bleed, stuffy nose (nasal congestion), throat irritation, runny nose 

(rhinorrhoea) 
• inflammation of the peritoneum (the tissue that lines most of the organs of the abdomen), constipation, 

stomach discomfort after meals (dyspepsia), abdominal distension  
• hives, redness of the skin, dry skin, red or purple spots under the skin, increased sweating 



53 

• muscle cramp, muscle aches, back and neck pain, bone pain, joint swelling, pain in the limbs (arms and 
legs) 

• kidney disorder, difficulties or pain when urinating (dysuria), blood in urine 
• spontaneous penile erection 
• swelling (edema), chest discomfort, feeling of weakness (asthenia), chest pain, infusion site pain, chills  
• increase of liver enzymes, decrease of the proportion of blood volume that is occupied by red blood 

cells, decrease in the protein in red blood cells that carries oxygen 
• infusion related reaction 
 
Rare: may affect up to 1 in 1,000 people: 
• infection by fungi (Aspergillus infection), infection of the joint (arthritis bacterial),  Haemophilus 

influenzae infection, gum infection, impetigo, bacterial sexual transmitted disease (gonorrhea) 
• skin tumor (melanoma), bone marrow disorder 
• destruction of red blood cells (haemolysis), clumping of cells, abnormal clotting factor, abnormal 

blood clotting, 
• disease with thyroid overactivity (Basedow’s disease) 
• sleep disorder, abnormal dreams 
• fainting 
• irritation of eye 
• bruise 
• unusual backflow of food from stomach, gum pain 
• yellowing of the skin and/or eyes (jaundice) 
• inflammation of the skin, skin color disorder 
• spasm of mouth muscle   
• menstrual disorder 
• abnormal leakage of the infused drug out of the vein, infusion site abnormal sensation, feeling hot 
 
Reporting of side effects  
If you get any side effects, talk to your doctor or pharmacist 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 Soliris 
 
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 – 8°C).  
Do not freeze. 
Soliris vials in the original package may be removed from refrigerated storage for only one single period 
of up to 3 days. At the end of this period the product can be put back in the refrigerator. 
Store in the original package in order to protect from light. 
After dilution, the product should be used within 24 hours. 
 
Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines you 
no longer use. These measures will help protect the environment. 
 
6. Contents of the pack and other information 
 
What Soliris contains 
 

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


54 

− The active substance is eculizumab (300 mg/30 ml in a vial corresponding to 10 mg/ml). 
 
− The other ingredients are:  

- sodium phosphate monobasic  
- sodium phosphate dibasic  
- sodium chloride 
- polysorbate 80 (vegetable origin) 

Solvent: water for injections 
 
What Soliris looks like and contents of the pack 
Soliris is presented as a concentrate for solution for infusion (30 ml in a vial – pack size of 1).  
Soliris is a clear and colorless solution. 
 
 
Marketing Authorisation Holder 
Alexion Europe SAS 
103-105 rue Anatole France 
92300 Levallois-Perret 
France 
 
Manufacturer 
Almac Pharma Services 
22 Seagoe Industrial Estate 
Craigavon BT63 5QD 
United Kingdom 
 
Patheon Italia S.p.A 
Viale G. B. Stucchi, 110 
20900 Monza (MB) 
Italy 
 
Alexion Pharma International Operations 
Unlimited Company 
College Business and Technology Park 
Blanchardstown 
Dublin 15 
Ireland 

 

 
 
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/. There are also links to other websites about rare diseases and treatments. 

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


55 

--------------------------------------------------------------------------------------------------------------------------- 
Instructions for Use for Healthcare Professionals 

Handling Soliris 
 

The following information is intended for medical or healthcare professionals only:  
 

1- How is Soliris supplied? 
Each vial of Soliris contains 300 mg of active ingredient in 30 ml of product solution. 
 
2- Before Administration 
Reconstitution and dilution should be performed in accordance with good practices rules, particularly for 
the respect of asepsis. 
Soliris should be prepared for administration by a qualified healthcare professional using aseptic 
technique.  
• Inspect visually Soliris solution for particulate matter and discolouration. 
• Withdraw the required amount of Soliris from the vial(s) using a sterile syringe. 
• Transfer the recommended dose to an infusion bag. 
• Dilute Soliris to a final concentration of 5 mg/ml (initial concentration divided by 2) by adding the 

appropriate amount of diluent to the infusion bag. For 300 mg doses, use 30 ml of Soliris (10 mg/ml) 
and add 30 ml of diluent. For 600 mg doses, use 60 ml of Soliris and add 60 ml of diluent. For 900 mg 
doses, use 90 ml of Soliris and add 90 ml of diluent. For 1,200 mg doses, use 120 ml of Soliris and add 
120 ml of diluent. The final volume of a 5 mg/ml diluted Soliris solution is 60 ml for 300 mg doses, 
120 ml for 600 mg doses, 180 ml for 900 mg doses or 240 ml for 1,200 mg doses. 

• Diluents are Sodium chloride 9 mg/ml (0.9%) solution for injection, Sodium chloride 4.5 mg/ml 
(0.45%) solution for injection or 5% dextrose in Water. 

• Gently agitate the infusion bag containing the diluted Soliris solution to ensure thorough mixing of the 
medicinal product and diluent. 

• The diluted solution should be allowed to warm to room temperature [18°C – 25°C] prior to 
administration by exposure to ambient air. 

• The diluted solution must not be heated in a microwave or with any heat source other than the 
prevailing room temperature. 

• Discard any unused portion left in a vial as the medicinal product contains no preservatives. 
• Diluted solution of Soliris may be stored at 2°C – 8°C for up to 24 hours prior to administration. 
 
3- Administration 
• Do not administer Soliris as an intravenous push or bolus injection. 
• Soliris should only be administered via intravenous infusion.  
• The diluted solution of Soliris should be administered by intravenous infusion over 25 to 45 minutes 

(35 minutes ± 10 minutes) in adults and 1-4 hours in paediatric patients under 18 years of age via 
gravity feed, a syringe-type pump, or an infusion pump. It is not necessary to protect the diluted 
solution of Soliris from light during administration to the patient. 

The patient should be monitored for one hour following infusion. If an adverse event occurs during the 
administration of Soliris, the infusion may be slowed or stopped at the discretion of the physician. If the 
infusion is slowed, the total infusion time may not exceed two hours in adults and four hours in paediatric 
patients under 18 years of age. 
 
4- Special Handling and Storage 
Store in a refrigerator (2°C – 8°C). Do not freeze. Store in the original package in order to protect from 
light. Soliris vials in the original package may be removed from refrigerated storage for only one single 
period of up to 3 days. At the end of this period the product can be put back in the refrigerator.  
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. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURERS 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