Kanuma

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
  



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This medicinal product is subject to additional monitoring. This will allow quick identification of new 
safety information. Healthcare professionals are asked to report any suspected adverse reactions. See 
section 4.8 for how to report adverse reactions. 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
KANUMA 2 mg/ml concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of concentrate contains 2 mg sebelipase alfa*.  
 
Each vial of 10 ml contains 20 mg sebelipase alfa. 
 
*produced in egg white of transgenic Gallus by recombinant DNA (rDNA) technology. 
 
Excipient with known effect  
Each vial contains 33 mg sodium. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion (sterile concentrate). 
 
Clear to slightly opalescent, colourless to slightly coloured solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
KANUMA is indicated for long-term enzyme replacement therapy (ERT) in patients of all ages with 
lysosomal acid lipase (LAL) deficiency. 
 
4.2 Posology and method of administration 
 
KANUMA treatment should be supervised by a healthcare professional experienced in the management 
of patients with LAL deficiency, other metabolic disorders, or chronic liver diseases. KANUMA should 
be administered by a trained healthcare professional who can manage medical emergencies.  
 
Posology 
 
It is important to initiate treatment as early as possible after diagnosis of LAL deficiency. 
 
For instructions on the preventive measures and monitoring of hypersensitivity reactions, see section 4.4. 
Following the occurrence of a hypersensitivity reaction, appropriate pre-treatment should be considered 
according to the standard of care (see section 4.4). 



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Infants (< 6 months of age)  
The recommended starting dose in infants (< 6 months of age) presenting with rapidly progressive LAL 
deficiency is 1 mg/kg administered as an intravenous infusion once weekly. Dose escalation to 3 mg/kg 
once weekly should be considered based on clinical response. 
 
Children and adults  
The recommended dose in children and adults who do not present with rapidly progressive LAL 
deficiency prior to 6 months of age is 1 mg/kg administered as an intravenous infusion once every other 
week.  
 
Special populations 
 
Renal impairment 
No dosing adjustment is recommended in patients with renal impairment based on current knowledge of 
the pharmacokinetics and pharmacodynamics of sebelipase alfa (see section 5.2). 
 
Hepatic impairment 
No dosing adjustment is recommended in patients with hepatic impairment based on current knowledge 
of the pharmacokinetics and pharmacodynamics of sebelipase alfa (see section 5.2). 
 
Elderly population (≥ 65 years old)  
The safety and efficacy of sebelipase alfa in patients older than 65 years have not been evaluated and no 
alternative dose regimens can be recommended for these patients (see section 5.1).  
 
Overweight patients  
The safety and efficacy of sebelipase alfa in overweight patients have not been thoroughly evaluated and 
therefore no alternative dose regimens can be recommended for these patients at this time. 
 
Paediatric population 
Administration of sebelipase alfa to infants with confirmed multiple-organ failure should be at the 
discretion of the treating physician. 
 
Method of administration  
 
KANUMA is for intravenous use only.  
 
The total volume of the infusion should be administered over approximately 2 hours. A 1-hour infusion 
may be considered after patient tolerability is established. The infusion period may be extended in the 
event of dose escalation. 
 
KANUMA should be administered through a 0.2 μm filter (see section 6.6). 
 
For instructions on dilution of the medicinal product before administration, see section 6.6. 
 
4.3 Contraindications 
 
Life-threatening hypersensitivity (anaphylactic reaction) to the active substance when attempts to 
rechallenge are unsuccessful, or to egg or any of the excipients listed in section 6.1, (see section 4.4). 
 
4.4 Special warnings and precautions for use 



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Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number of 
the administered medicinal product should be clearly recorded. 
 
Hypersensitivity reactions including anaphylaxis  
 
Hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with sebelipase 
alfa; see section 4.8. Therefore, appropriate medical support must be readily available when sebelipase 
alfa is administered. If severe reactions occur, the sebelipase alfa infusion should be immediately stopped 
and appropriate medical treatment should be initiated. The risks and benefits of re-administering 
sebelipase alfa following a severe reaction should be considered. 
 
Following the first sebelipase alfa infusion, including the first infusion after a dose escalation, patients 
should be observed for 1 hour in order to monitor for any signs or symptoms of anaphylaxis or a severe 
hypersensitivity reaction. 
 
The management of hypersensitivity reactions may include temporarily interrupting the infusion, 
lowering the infusion rate, and/or treatment with antihistamines, antipyretics, and/or corticosteroids.  
For patients who have experienced allergic reactions during infusion, caution should be exercised upon 
re-administration. If interrupted, the infusion may be resumed at a slower rate with increases as tolerated. 
Pre-treatment with antipyretics and/or antihistamines may prevent subsequent reactions in those cases 
where symptomatic treatment was required.  
 
In cases of severe infusion reactions and in cases of lack or loss of effect, patients should be tested for the 
presence of antibodies. 
 
This medicinal product may contain traces of egg proteins. Patients with known egg allergies were 
excluded from clinical studies (see section 4.3).  
 
Excipients 
 
This medicinal product contains 33 mg sodium per vial equivalent to 1.7% of the WHO recommended 
maximum daily intake of 2 g sodium for an adult. It is administered in sodium chloride 9 mg/ml (0.9%) 
solution for infusion (see section 6.6). This 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. 
 
Because it is a recombinant human protein, sebelipase alfa is an unlikely candidate for cytochrome P450 
mediated or other drug-drug interactions. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 



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There are no data from the use of sebelipase alfa in pregnant women. Animal studies do not indicate 
direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a 
precautionary measure, it is preferable to avoid use of sebelipase alfa during pregnancy. 
 
Breast-feeding 
 
There are no data from studies in breast-feeding women. It is not known whether sebelipase alfa is 
excreted in human milk. A decision must be made whether to discontinue breast-feeding or to 
discontinue/abstain from sebelipase alfa therapy taking into account the benefit of breast-feeding for the 
child and the benefit of therapy for the woman. 
 
Fertility 
 
There are no clinical data on the effects of sebelipase alfa on fertility. Animal studies show no evidence of 
impaired fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
KANUMA has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of safety profile 
 
The most serious adverse reactions experienced by 3% of patients in clinical studies were signs and 
symptoms consistent with anaphylaxis. Signs and symptoms included chest discomfort, conjunctival 
injection, dyspnoea, generalised and itchy rash, hyperaemia, mild eyelid oedema, rhinorrhoea, severe 
respiratory distress, tachycardia, tachypnoea and urticaria.  
 
Tabulated list of adverse reactions 
 
The data in Table 1 describe adverse reactions reported in infants who received sebelipase alfa in clinical 
studies at doses up to 3 mg/kg weekly. The data in Table 2 describe adverse reactions reported in children 
and adults who received sebelipase alfa in clinical studies at a dose of 1 mg/kg once every other week.  
 
Adverse reactions are listed by system organ class and frequency. Frequencies are defined according to 
the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to 
< 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be estimated from 
the available data). Within each frequency grouping, adverse reactions are presented in order of 
decreasing seriousness. 
 
Table 1: Adverse reactions reported in infantsc receiving sebelipase alfa 
MedDRA System organ class Frequencya MedDRA preferred term 
Immune system disorders Very common Eyelid oedema 
Psychiatric disorders Very common Agitationb, irritabilityb 
Nervous system disorders Very common Hypotonia 
Cardiac disorders Very common Tachycardiab 
Vascular disorders Very common Hypertension, pallorb 



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Respiratory, thoracic and mediastinal 
disorders Very common 

Respiratory distress, wheezing, cough, 
rhinitis, nasal congestion, sneezing 

Gastrointestinal disorders Very common Diarrhoea, gastro-oesophageal reflux disease, retching, vomitingb 

Skin and subcutaneous tissue disorders Very common Urticaria
b, rashb, eczemab, pruritis, rash 

maculo-papular 
General disorders and administration site 
conditions Very common Chills, hyperthermia, pyrexia

b, oedema 

Investigations Very common 

Body temperature increased, oxygen 
saturation decreased, blood pressure 
increased, heart rate increased, 
respiratory rate increased 

a Very common = Reported in ≥ 1 patient receiving sebelipase alfa 
b Reported in ≥ 2 patients receiving sebelipase alfa 
c Age at first dose: 1 to 6 months 
 
Table 2: Adverse reactions reported in children and adultsd receiving sebelipase alfa 
MedDRA System organ class Frequencya MedDRA preferred term 
Infections and infestations Common Urinary tract infection 
Immune system disorders Common Anaphylactic reaction, eyelid oedema 

Metabolism and nutrition disorders Common Transient hypercholesterolaemia, transient hypertriglyceridaemia 
Psychiatric disorders Common Anxietyc, insomnia 
Nervous system disorders Common Dizziness 

Cardiac disorders Common Tachycardia  
Vascular disorders Common Hyperaemiae, hypotension 

Respiratory, thoracic and mediastinal 
disorders Common Laryngeal oedema

e, dyspnoeab,c,e,  

Gastrointestinal disorders Common Diarrhoea
b,e, abdominal painb,e, 

abdominal distension, nauseab e 

Skin and subcutaneous tissue disorders Common 
Urticaria, rashc,e (including rash 
papular and rash pruritic), prurituse, 
eczemae 

Reproductive system and breast 
disorders Common Menorrhagia 

General disorders and administration site 
conditions Common 

Chills, chest discomfortc,e, oedema, 
fatigue, infusion site induration, 
pyrexia 

Investigations Common Body temperature increasedb,c 
Injury, poisoning and procedural 
complications Common Infusion related reaction

c 
a Common = Reported in ≥ 1 patient receiving sebelipase alfa  
b Reported at the same frequency in patients receiving sebelipase alfa or placebo or more frequently in 

patients receiving placebo during the double-blind period of LAL-CL02  
c Reported as part of an adverse reaction in a single patient receiving sebelipase alfa in LAL-CL02  
d Age at first dose: 4 to 58 years 
e Reported in ≥ 2 patients receiving sebelipase alfa 



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Description of selected adverse reactions 
 
Hypersensitivity 
Three patients of 106 (3%) patients treated with sebelipase alfa, including 1 of 14 (7%) infants and 
2 of 92 (2%) children and adults, in clinical studies experienced signs and symptoms consistent with 
anaphylaxis. Anaphylaxis occurred during the infusion as late as 1 year after treatment initiation. 
 
In clinical studies, 21 of 106 (20%) sebelipase alfa-treated patients, including 9 of 14 (64%) infants and 
12 of 92 (13%) children and adults, experienced signs and symptoms either consistent with or that may be 
related to a hypersensitivity reaction. These reported signs and symptoms occurring in two or more 
patients included abdominal pain, agitation, chills, diarrhoea, eczema, hypertension, irritability, laryngeal 
oedema, nausea, oedema, pallor, pruritus, pyrexia/body temperature increased, rash, tachycardia, 
urticaria, and vomiting. The majority of reactions occurred during or within 4 hours of the completion of 
the infusion. 
 
Transient hyperlipidaemia  
Consistent with its known mechanism of action, asymptomatic increases in circulating cholesterol and 
triglycerides have been observed following initiation of treatment. These increases have generally 
occurred within the first 2 to 4 weeks and improved within a further 8 weeks of treatment. See section 5.1. 
 
Immunogenicity  
Patients have developed anti-drug antibodies (ADA) to sebelipase alfa. Based on the limited data 
currently available the development of ADA seems to occur more frequently in infants.’ 
 
In LAL-CL03, 4 of 7 evaluable infants (57%) developed ADA during treatment with sebelipase alfa. At 
the time of initial ADA positivity, 3 patients were receiving a dose of 1 mg/kg once weekly and 1 patient 
was receiving a dose of 3 mg/kg once weekly. Most patients who developed ADA did so within the first 
2 months of exposure. ADA titres decreased to undetectable levels during continued treatment in 3 of the 
4 patients. Two patients were determined to be positive for antibodies that inhibit in vitro enzyme activity 
and cellular uptake of the enzyme. In a separate study in infants, one of five evaluable patients developed 
antibodies that inhibit in vitro enzyme activity and cellular uptake of the enzyme.  
 
In LAL-CL02, 5 of 35 evaluable children and adults (14%) who were administered sebelipase alfa during 
the 20-week double-blind period of the study developed ADA. All patients were receiving 1 mg/kg once 
every other week. Those patients who developed ADA did so within the first 3 months of exposure. ADA 
titres decreased to undetectable levels during continued treatment in all patients. Two patients were 
positive at only a single time point. No patients developed antibodies that inhibited in vitro enzyme 
activity and one patient developed antibodies that inhibited cellular uptake of the enzyme in vitro.  
 
The association between the development of ADA to sebelipase alfa and reductions in treatment effect or 
the occurrence of adverse reactions has not been determined. 
 
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 
 

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


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In clinical studies, doses of sebelipase alfa were explored up to 5 mg/kg once weekly and no specific 
signs or symptoms were identified following the higher doses. For management of adverse reactions, see 
sections 4.4 and 4.8. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other alimentary tract and metabolism products, Enzymes; ATC code: 
A16AB14 
 
Lysosomal acid lipase (LAL) deficiency  
 
LAL deficiency is a rare disease associated with significant morbidity and mortality, which affects 
individuals from infancy through adulthood. LAL deficiency presenting in infants is a medical emergency 
with rapid disease progression over a period of weeks that is typically fatal within the first 6 months of 
life. LAL deficiency is an autosomal recessive lysosomal storage disorder characterised by a genetic 
defect resulting in a marked decrease or loss in activity of the lysosomal acid lipase (LAL) enzyme. 
 
Deficient LAL enzyme activity results in the lysosomal accumulation of cholesteryl esters and 
triglycerides. In the liver, this accumulation leads to hepatomegaly, increased hepatic fat content, 
transaminase elevation signaling chronic liver injury, and progression to fibrosis, cirrhosis, and 
complications of end stage liver disease. In the spleen, LAL deficiency results in splenomegaly, anemia, 
and thrombocytopenia. Lipid accumulation in the intestinal wall leads to malabsorption and growth 
failure. Dyslipidemia is common with elevated LDL and triglycerides and low HDL, associated with 
increase liver fat content and transaminase elevations. In addition to liver disease, patients with LAL 
deficiency experience increased risk for cardiovascular disease and accelerated atherosclerosis.  
 
Mechanism of action  
 
Sebelipase alfa is a recombinant human lysosomal acid lipase (rhLAL). 
 
Sebelipase alfa binds to cell surface receptors via glycans expressed on the protein and is subsequently 
internalised into lysosomes. Sebelipase alfa catalyses the lysosomal hydrolysis of cholesteryl esters and 
triglycerides to free cholesterol, glycerol and free fatty acids. Replacement of LAL enzyme activity leads 
to reductions in liver fat content and transaminases, and enables metabolism of cholesteryl esters and 
triglycerides in the lysosome, leading to reductions in low-density lipoprotein (LDL) cholesterol and non-
high-density lipoprotein (HDL) cholesterol, triglycerides, and increases in HDL cholesterol. Improvement 
in growth occurs as a result of substrate reduction in the intestine. 
 
Clinical studies 
 
Infants presenting with LAL deficiency 
LAL-CL03 was a multicentre, open-label, single-arm study of sebelipase alfa in 9 patients with LAL 
deficiency with growth failure or other evidence of rapidly progressive disease prior to 6 months of age. 
Patients also had rapidly progressive liver disease and severe hepatosplenomegaly. The age range at study 
entry was 1-6 months. Patients received sebelipase alfa at 0.35 mg/kg once weekly for the first 2 weeks 
and then 1 mg/kg once weekly. Based on clinical response, dose escalation to 3 mg/kg once weekly 
occurred as early as 1 month and up to 20 months after starting treatment at 1 mg/kg. A further dose 
escalation to 5 mg/kg once weekly was allowed.  



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Efficacy was assessed by comparing the survival experience of sebelipase alfa-treated patients who 
survived past 12 months of age in LAL-CL03 with a historical cohort of untreated infants presenting with 
LAL deficiency with similar clinical characteristics. In LAL-CL03, 6 of 9 sebelipase alfa-treated infants 
survived beyond 12 months (67% 12-month survival, 95% CI: 30% to 93%). With continued treatment 
beyond 12 months of age, 1 additional patient died at age 15 months. In the historical cohort, 0 of 
21 patients survived beyond 8 months of age (0% 12-month survival, 95% CI: 0% to 16%).  
 
Sebelipase alfa at doses up to 1 mg/kg once weekly resulted in improvements in alanine aminotransferase 
(ALT) and aspartate aminotransferase (AST) levels and weight gain within the first several weeks of 
treatment. From baseline to week 48, the mean reductions for ALT and AST were -34.0 U/l and -44.5 U/l, 
respectively. Dose escalation to 3 mg/kg once weekly was associated with additional improvements in 
weight gain, lymphadenopathy and serum albumin. From baseline to week 48, mean weight-for-age 
percentile improved from 12.74% to 29.83% and mean serum albumin levels increased from 26.7 g/l to 
38.7 g/l. 
 
One infant was treated with 5 mg/kg once weekly in LAL-CL03; no new adverse reactions were reported 
at this dose. In the absence of more clinical data, this dose is not recommended. 
 
Children and adults with LAL deficiency 
LAL-CL02 was a multicentre, double-blind, placebo-controlled study in 66 children and adults with LAL 
deficiency. Patients were randomised to receive sebelipase alfa at a dose of 1 mg/kg (n = 36) or placebo 
(n = 30) once every other week for 20 weeks in the double-blind period. The age range at randomisation 
was 4-58 years old (71% were < 18 years old). For study entry, patients were required to have ALT levels 
of ≥1.5 X upper limit of normal (ULN). The majority of patients (58%) had LDL-cholesterol > 190 mg/dl 
at study entry, and 24% of patients with LDL-cholesterol > 190 mg/dl were on lipid lowering medicinal 
products. Of the 32 patients who had a liver biopsy at study entry, 100% had fibrosis and 31% had 
cirrhosis. The age range of patients with biopsy evidence of cirrhosis was 4-21 years old. 
 
The following endpoints were assessed: normalisation of ALT, decrease in LDL-cholesterol, decrease in 
non-HDL-cholesterol, normalisation of AST, decrease in triglycerides, increase in HDL-cholesterol, 
decrease in liver fat content assessed by multi-echo gradient echo magnetic resonance imaging (MEGE-
MRI), and improvement in hepatic steatosis measured by morphometry. 
 
A statistically significant improvement in multiple endpoints was observed in the sebelipase alfa-treated 
group as compared to the placebo group at the completion of the 20-week double-blind period of the 
study, as shown in Table 3. The absolute reduction in mean ALT level was -57.9 U/l (-53%) in the 
sebelipase alfa-treated group and -6.7 U/l (-6%) in the placebo group. 
 

Table 3: Primary and secondary efficacy endpoints in LAL-CL02 

Endpoint 
sebelipase 

alfa 
(n = 36) 

Placebo 
(n = 30) P-value

d 

Primary Endpoint    
Normalisation of ALTa 31% 7% 0.0271 
Secondary Endpoints    
LDL-cholesterol, mean % change from baseline -28% -6% < 0.0001 
Non-HDL-cholesterol, mean % change from baseline -28% -7% < 0.0001 



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Table 3: Primary and secondary efficacy endpoints in LAL-CL02 

Endpoint 
sebelipase 

alfa 
(n = 36) 

Placebo 
(n = 30) P-value

d 

Normalisation of ASTb 42% 3% 0.0003 
Triglycerides, mean % change from baseline -25% -11% 0.0375 
HDL-cholesterol, mean % change from baseline  20% -0.3% < 0.0001 
Liver fat content c, mean % change from baseline -32% -4% < 0.0001 

a Proportion of patients who achieved normalisation defined as 34 or 43 U/l, depending on age and 
gender. 

b Proportion of patients who achieved normalisation defined as 34-59 U/l, depending on age and gender. 
Evaluated in patients with abnormal baseline values (n = 36 for sebelipase alfa; n = 29 for placebo).  

c Evaluated in patients with MEGE-MRI assessments performed (n = 32 for sebelipase alfa; n = 25 for 
placebo).  

d P-values are from Fisher’s exact test for normalisation endpoints and Wilcoxon rank-sum test for all 
other endpoints. 

 
Paired liver biopsies at baseline and week 20 were available in a subset of patients (n = 26). Of patients 
with paired liver biopsies, 63% (10/16) of sebelipase alfa-treated patients had improvement in hepatic 
steatosis (at least ≥ 5% reduction) as measured by morphometry compared to 40% (4/10) of placebo 
patients. This difference was not statistically significant.  
 
Open-label period 
Sixty-five of 66 patients entered the open-label period (up to 130 weeks) at a sebelipase alfa dose of 
1 mg/kg once every other week. In patients who had received sebelipase alfa during the double-blind 
period, reductions in ALT levels during the first 20 weeks of treatment were maintained and further 
improvements were seen in lipid parameters including LDL-cholesterol and HDL-cholesterol levels. Four 
(4) of 65 patients in the open label period were dose escalated to 3 mg/kg once every other week based on 
clinical response. 
 
Placebo patients had persistently elevated serum transaminase and abnormal serum lipid levels during the 
double-blind period. Consistent with what was observed in sebelipase alfa-treated patients during the 
double-blind period, initiation of treatment with sebelipase alfa during the open-label period produced 
rapid improvements in ALT levels and in lipid parameters including LDL-cholesterol and 
HDL-cholesterol levels.  
 
In a separate open-label study (LAL-CL01/LAL-CL04) in adult patients with LAL deficiency, 
improvements in serum transaminase and lipid levels were sustained through the 104-week treatment 
period. 
 
Paediatric population 
 
Fifty-six of 84 patients (67%) who received sebelipase alfa during clinical studies (LAL-CL01/LAL-
CL04, LAL-CL02 and LAL-CL03) were in the paediatric and adolescent age range (1 month up to 
18 years).  
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
sebelipase alfa in one or more subsets of the paediatric population in LAL deficiency (see section 4.2 for 
information on paediatric use). 



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LAL deficiency registry 
 
Medical or healthcare professionals are encouraged to participate and enrol all patients diagnosed with 
LAL deficiency in the LAL deficiency registry. 
 
5.2 Pharmacokinetic properties 
 
Children and adults 
 
The pharmacokinetics of sebelipase alfa in children and adults were determined using a population 
pharmacokinetic analysis of 65 patients with LAL deficiency who received intravenous infusions of 
sebelipase alfa at 1 mg/kg once every other week in LAL-CL02. Twenty-four patients were aged 4-
11 years, 23 were aged 12-17 years, and 18 were aged ≥ 18 years (Table 4). Based on a non-
compartmental analysis of data from adults (LAL-CL01/LAL-CL-04), the pharmacokinetics of sebelipase 
alfa appeared to be nonlinear with a greater than dose-proportional increase in exposure observed between 
the 1 and 3 mg/kg doses. No accumulation was seen at 1 mg/kg (once weekly or once every other week) 
or 3 mg/kg once weekly. 
 
 
 

Table 4: Mean Population Pharmacokinetic Parameters 

Pharmacokinetic 
parameter 

Study LAL-CL02 – Children and Adults 
1 mg/kg once every other week 

4-11 years old 
N=24 

12-17 years old 
N=23 

≥ 18 years old 
N=18 

Week 0 Week 22* Week 0 Week 22* Week 0 Week 22* 
AUCss (ng∙hr/mL) 1133.8 941.6 1436.4 1453.6 1989.3 1861.0 

Cmax (ng/mL) 571.7 489.6 736.4 783.6 1076.9 957.0 
Tmax (hr) 1.2 1.3 1.2 1.1 1.4 1.3 

CL (L/hr) 28.8 31.1 35.1 37.4 36.4 38.2 
Vc (L) 3.3 3.6 5.0 5.4 5.5 5.3 

T1/2 (hr) 0.1 0.1 0.1 0.1 0.1 0.1 
* Week 22 for placebo patients reset to Week 0, i.e. first week of active treatment. 
AUCss = Area under the plasma concentration time curve at steady-state 
Cmax = Maximum concentration 
Tmax = Time to maximum concentration 
CL = Clearance 
Vc = Central volume of distribution 
T1/2 = Half-life 
 

Infants (< 6 months of age) 
 
In LAL-CL03, sebelipase alfa was eliminated from the systemic circulation with a median T1/2 of 0.1 hr 
(range: 0.1-0.2) at the 3 mg/kg once weekly dose (n = 4). The difference in exposures to sebelipase alfa 
between the once weekly 0.35 mg/kg and 3 mg/kg groups was more than dose proportional, with a 
8.6-fold increase in dose resulting in a 9.6-fold increase in exposure for AUC and a 10.0-fold increase for 
Cmax. 
 
Linearity/non-linearity 



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Based on these data, the pharmacokinetics of sebelipase alfa appeared to be nonlinear with a greater than 
dose-proportional increase in exposure observed between the 1 and 3 mg/kg dose. 
 
Special populations 
 
During the covariate analysis of the population pharmacokinetics model for sebelipase alfa, age, body 
weight, and sex were not found to have a significant influence on CL and Vc of sebelipase alfa. 
Sebelipase alfa has not been investigated in patients 2 to 4 years of age or patients aged 65 years or older.  
 
There is limited information of sebelipase alfa pharmacokinetics in non-Caucasian ethnic groups.  
 
Sebelipase alfa is a protein and is expected to be metabolically degraded through peptide hydrolysis. 
Consequently, impaired liver function is not expected to affect the pharmacokinetics of sebelipase alfa. 
There is a lack of data in patients with severe hepatic impairment. 
 
Renal elimination of sebelipase alfa is considered a minor pathway for clearance. There is a lack of data 
in patients with renal impairment. 
 
There is limited information on the impact of ADA on sebelipase alfa pharmacokinetics. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated-dose toxicity in rats and monkeys, or fertility, embryo-foetal and peri- and 
postnatal development in rats and rabbits. Chronic toxicity studies in juvenile cynomolgous monkeys 
showed no toxicity at doses up to 3 times the recommended dose in infants and 10 times the 
recommended dose in adults/children. No adverse findings were observed in rat and rabbit embryofoetal 
development studies at doses up to at least 10 times the adult/children recommended dose and in rat 
fertility and peri- postnatal development studies at doses up to 10 times the adult/children recommended 
dose.  
 
Studies to evaluate the mutagenic and carcinogenic potential of sebelipase alfa have not been performed. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium citrate 
Citric acid monohydrate 
Human serum albumin 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 



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Unopened vials: 2 years.  
 
After dilution: Chemical and physical in-use stability has been demonstrated for up to 24 hours at 2 °C to 
8 °C, or up to 12 hours below 25 °C. 
 
From a microbiological point of view, the diluted solution should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are the responsibility of the user and would 
normally not be longer than 24 hours at 2 °C to 8 °C, or up to 12 hours below 25 °C, unless dilution has 
taken place in controlled and validated aseptic conditions. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2 °C to 8 °C).  
Do not freeze.  
Store in the original package in order to protect from light. 
 
For storage conditions after dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Clear glass vial (Type I) with a siliconised butyl rubber stopper, and an aluminium seal with a plastic flip-
off cap, containing 10 ml of concentrate. 
 
Pack size: 1 vial. 
 
6.6 Special precautions for disposal and other handling 
 
Each vial of KANUMA is intended for single use only. KANUMA has to be diluted with sodium chloride 
9 mg/ml (0.9%) solution for infusion using aseptic technique.  
The diluted solution should be administered to patients using a low-protein binding infusion set equipped 
with an in-line, low-protein binding 0.2 μm filter, with a surface area of greater than 4.5 cm2 as available 
in order to avoid filter occlusion. 
 
Preparation of the sebelipase alfa infusion  
 
KANUMA should be prepared and used according to the following steps. Aseptic technique should be 
used. 
a. The number of vials to be diluted for infusion should be determined based on the patient’s weight 

and prescribed dose. 
b. It is recommended to allow KANUMA vials to reach a temperature between 15 °C and 25 °C prior 

to dilution to minimise the potential for the formation of sebelipase alfa protein particles in 
solution. The vials should not be left outside the refrigerator longer than 24 hours prior to dilution 
for infusion. The vials should not be frozen, heated or microwaved and should be protected from 
light. 

c. The vials should not be shaken. Prior to dilution, the concentrate in the vials should be inspected 
visually; the concentrate should be clear to slightly opalescent, colourless to slightly coloured 
(yellow). Due to the proteinaceous nature of the medicinal product, slight flocculation (e.g., thin 
translucent fibres) may be present in the vial concentrate and is acceptable for use. 

d. Do not use if the concentrate is cloudy, or if foreign particulate matter is present.  



14 

e. Up to 10 ml of concentrate should be slowly withdrawn from each vial and diluted with sodium 
chloride 9 mg/ml (0.9%) solution for infusion. See table 5 for recommended total infusion volumes 
by weight range. The solution should be mixed gently, and not be shaken. 

 
Table 5: Recommended infusion volumes (1 mg/kg dose)* 

Weight range (kg) Total infusion volume (ml) 
1-10 10 

11-24 25 
25-49 50 
50-99 100 

100-120 250 
* The infusion volume should be based on the prescribed dose and should be prepared to a final 
sebelipase alfa concentration of 0.1-1.5 mg/ml. 
 
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/1/15/1033/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28 August 2015 
Date of latest renewal: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.  

  

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


15 

 

 

 

 

 

 

 

ANNEX II 

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

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 

USE OF THE MEDICINAL PRODUCT 
 

 



16 

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

Name and address of the manufacturer of the biological active substance  

Fujifilm Diosynth Biotechnologies USA Inc 
6051 George Watts Hill Drive 
Research Triangle Park 
North Carolina 
NC 27709 
UNITED STATES 

Name and address of the manufacturer responsible for batch release 

Almac Pharma Services Ltd. 
Seagoe Industrial Estate 
Craigavon 
Co Armagh 
BT63 5UA 
United Kingdom 
 
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. 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION  

• Periodic safety update reports (PSURs) 
 

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 

 
 
 



17 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 
USE OF THE MEDICINAL PRODUCT   

• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities and 
interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation and 
any agreed subsequent updates of the RMP. 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

• Additional risk minimisation measures 
 
Prior to launch of Kanuma in each Member State, the Marketing Authorisation Holder (MAH) must 
agree about the content and format of the educational material including communication media, 
distribution modalities, and any other aspects of the programme, with the National Competent Authority.  

The educational material is aimed to encourage healthcare professionals to enrol patients in the 
prospective disease and clinical outcome registry of patients with Lysosomal Acid Lipase (LAL) 
Deficiency to monitor for efficacy and safety of Kanuma (LAL Deficiency Registry), with particular 
regard to hypersensitivity reactions, including anaphylaxis, and anti-drug antibodies (ADA) 
development impacting response to drug. 

The MAH shall ensure that in each Member State where Kanuma is marketed, all healthcare 
professionals who are expected to use Kanuma have access to the educational material. The physician’s 
educational material should contain: 

- Summary of Product Characteristics  

- Guide for healthcare professionals   

The guide for healthcare professionals shall contain the following key elements: 

- Warning and precautions on the the risk of hypersensitivity including anaphylaxis or ADA 
development, with particular reference to symptoms, time to onset and severity.  

- Information on how to manage patients experiencing severe hypersensitivity reactions including 
anaphylaxis. 

- Details on how to monitor for potential ADA formation following initiation of treatment with 
Kanuma, particularly in patients on Kanuma who experience clinically important hypersensitivity 
reactions or potential loss of clinical response. 

- Information to healthcare professionals that it is the responsibility of the MAH to provide the test 
for the monitoring of ADA positive patients including the modalities for requesting the test. 

- Information on the ongoing LAL Deficiency Registry, including the importance of enrolling 
patients, also those not treated with Kanuma, and the modalities for participation. 

• Obligation to conduct post-authorisation measures  



18 

 
The MAH shall complete, within the stated timeframe, the below measures:  
 

Description  Due date 
Non-interventional post-authorisation safety study (PASS): LAL Deficiency 
Registry: Non-interventional, multicentre, prospective disease and clinical 
outcome registry of patients with Lysosomal Acid Lipase Deficiency to further 
understand the disease, its progression and any associated complication, and to 
evaluate the long-term efficacy  (normalisation of hepatic function)  and safety of 
Kanuma (in particular hypersensitivity reactions, including anaphylaxis, and 
anti-drug antibodies development potentially impacting response to drug) 
according to agreed protocol.  

Interim reports 
expected yearly  
 
Final study 
report expected 
in Jan 2027 

Study LAL-CL08: an open-label, Phase 2 study in infants with rapidly 
progressive LAL Deficiency to explore long-term safety and efficacy data. The 
efficacy objectives are assessment of hepatic function overtime up to 3 years and 
survival at 12 months. The safety objectives should focus on hypersensitivity 
reactions, particularly anti-drug antibodies development impacting response to 
drug.  

Final study 
report expected 
in July 2019 

 

  



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
  



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 
  



21 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
KANUMA 2 mg/ml concentrate for solution for infusion  
sebelipase alfa  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of concentrate contains 2 mg sebelipase alfa. Each vial contains 20 mg sebelipase alfa in 10 ml 
of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
Sodium citrate 
Citric acid monohydrate 
Human serum albumin 
Water for injections 
See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
1 vial of 10 ml 
20 mg/10 ml 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only. 
Read the package leaflet before use. 
Intravenous use after dilution. 
Do not shake. 
 
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 
 



22 

 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
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 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Alexion Europe SAS 
103-105 rue Anatole France 
92300 Levallois-Perret 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1033/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 



23 

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



24 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
10 ml VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
KANUMA 2 mg/ml sterile concentrate  
sebelipase alfa  
IV use after dilution  
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
20 mg/10 ml 
 
 
6. OTHER 
 
Store in a refrigerator  
Do not freeze.  
 
 
  



25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



26 

Package leaflet: Information for the user 
 

KANUMA 2 mg/ml concentrate for solution for infusion 
sebelipase alfa 

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

information. You can help by reporting any side effects you or your child may get. See the end of section 
4 for how to report side effects. 
 
Read all of this leaflet carefully before you are given 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. 
- If you get any side effects, talk to your doctor. This includes any possible side effects not listed in 

this leaflet. See section 4. 
 
 
What is in this leaflet 
 
1. What KANUMA is and what it is used for  
2. What you need to know before you are given KANUMA  
3. How KANUMA is given 
4. Possible side effects  
5. How to store KANUMA  
6. Contents of the pack and other information 
 
 
1. What KANUMA is and what it is used for 
 
KANUMA contains the active substance sebelipase alfa. Sebelipase alfa is similar to the naturally 
occurring enzyme lysosomal acid lipase (LAL), which the body uses to breakdown fats. It is used to treat 
patients of all ages with lysosomal acid lipase deficiency (LAL deficiency). 
 
LAL deficiency is a genetic disease that leads to liver damage, high blood cholesterol, and other 
complications due to a build-up of certain types of fats (cholesteryl esters and triglycerides). 
 
How KANUMA works 
This medicine is an enzyme replacement therapy. This means that it replaces the missing or defective 
LAL enzyme in patients with LAL deficiency. This medicine works by lowering the build-up of fat that 
causes medical complications, including impaired growth, liver damage and heart complications. It also 
improves blood levels of fats, including elevated LDL (bad cholesterol) and triglycerides.  
 
 
2. What you need to know before KANUMA is given 
 
You must not be given KANUMA 
- If you or your child has experienced life-threatening allergic reactions to sebelipase alfa that cannot 

be managed when you or your child receives the medicine again, or to egg or any of the other 
ingredients of this medicine (listed in section 6). 

 



27 

Warnings and precautions 
- If treated with KANUMA, you or your child may experience a side effect while you or your child 

is being given the medicine or during the hours following the infusion (see section 4). This is 
known as an infusion reaction which can sometimes be severe, and may include an allergic reaction 
that could be life-threatening and require medical treatment. The first time that you or your child 
are given KANUMA you should be observed by a healthcare professional for 1 hour to watch for 
any signs of an infusion reaction. If you or your child experiences a severe infusion reaction like 
this, seek immediate medical attention. If you or your child has an infusion reaction you or your 
child may be given additional medicines to treat or help prevent future reactions. These medicines 
may include antihistamines, fever-reducing medicines and/or corticosteroids (a type of anti-
inflammatory medicines). 
If the infusion reaction is severe, your doctor may stop KANUMA infusion and start giving you or 
your child appropriate medical treatment. 

- This medicine may contain egg proteins. If you or your child has an egg allergy or a history of 
allergies to eggs, tell your doctor or nurse (see You must not be given KANUMA).  

 
Other medicines and KANUMA 
Tell your doctor if you or your child are using, have recently used or might use any other medicines. 
 
Pregnancy  
There are no data from the use of sebelipase alfa in pregnant women. As a precautionary measure, you 
should not be given KANUMA if you are pregnant.  
 
Breast-feeding 
It is not known whether sebelipase alfa passes into breast milk. Tell your doctor if you are breast-feeding 
or plan to do so. Your doctor will then help you decide whether to stop breast-feeding, or whether to stop 
taking KANUMA, considering the benefit of breast-feeding to the baby and the benefit of KANUMA to 
the mother. 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your 
doctor for advice before taking this medicine.  
 
Driving and using machines 
KANUMA has no or negligible influence on the ability to drive and use machines. 
 
KANUMA contains sodium  
This medicine, when diluted with sodium chloride 9 mg/mL (0.9%) solution for injection for intravenous 
administration contains 33 mg sodium (main component of cooking/table salt) at the recommended dose. 
This is equivalent to 1.7% of the recommended maximum daily dietary intake of sodium for an adult. Tell 
your doctor if you or your child is on a controlled sodium diet.  
 
 
3. How KANUMA is given 
 
The dose you or your child receives is based on your or your child’s body weight. 
 
Infants (< 6 months of age) 
For patients who have signs and symptoms of the disease when they are infants, the recommended 
starting dose is 1 mg/kg once weekly. Dose adjustments may be considered based on how well you or 
your child responds to treatment.  
 



28 

Children and adults 
The recommended dose is 1 mg per kg body weight once every other week through a drip into a vein. 
 
Each infusion will take approximately 1 to 2 hours. You or your child may be monitored by your doctor 
or nurse for an additional hour after the infusion. KANUMA should be started at as young an age as 
possible and is intended for long-term use. 
 
Your doctor or nurse will give KANUMA to you or your child by an infusion (drip) into a vein. The 
medicine will be diluted before being given to you or your child.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Side effects were seen while patients were being given the medicine or shortly after (infusion reactions). 
The most serious side effects may include an allergic reaction (seen very commonly [may affect more 
than 1 in 10 people] in infants younger than 6 months old, or commonly [may affect up to 1 in 10 people] 
in children and adults) with symptoms including difficulty breathing, swelling of the throat, rapid 
breathing, fast heartbeat, chest discomfort, mild swelling of eyelids, red eyes, runny nose, flushing, and 
hives. If you or your child experiences symptoms like these, seek immediate medical attention. If 
you or your child has an infusion reaction you or your child may be given additional medicines to treat or 
help prevent future reactions. If the infusion reaction is severe, your doctor may stop the infusion of 
KANUMA in the vein and start giving appropriate medical treatment. 
 
Very common (may affect more than 1 in 10 people) side effects reported in infants (1 to 6 months old) 
are:  
 

eyelid swelling agitation high blood pressure 
decreased muscle tone  difficulty breathing wheezing 
paleness stuffy or swollen nose sneezing 
cough  heartburn (reflux diseases) dry heaving 
diarrhoea  hives rash 
vomiting  itching raised rash 
red swollen skin fever swelling 
chills  rapid breathing decreased oxygen in the blood  
fast heartbeat irritability  

 
Common (may affect up to 1 in 10 people) side effects reported in children and adolescents (4 to 18 years 
old) and adults are:  
 

severe allergic reaction 
(anaphylactic reaction) 

infection of the urinary system swelling of the eyelids 

temporary increased cholesterol 
or triglyceride (fats) levels in 
the blood 

fast heartbeat anxiety 

Sleeplessness Dizziness low blood pressure 
redness in face shortness of breath swelling of the throat 
Diarrhoea stomach ache stomach bloating 
Nausea Hives rash 



29 

Itching red swollen skin increased menstrual bleeding 
Shivers chest discomfort swelling 
Tiredness hardened area around the 

infusion site 
fever 

 
Frequency, type and severity of adverse reactions in children are the same as in adults.  
 
Reporting of side effects 
If you or your child gets any side effects, talk to your doctor. 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 KANUMA  
 
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 label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2 °C to 8 °C). Do not freeze. Do not shake. Store in the original package in order 
to protect from light. 
 
For diluted solutions, immediate use is recommended. If not used immediately, the diluted solution may 
be stored up to 24 hours at 2 °C to 8 °C or up to 12 hours below 25 °C. 
 
Do not throw away any medicines via wastewater or household waste. 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 KANUMA contains  
- The active substance is sebelipase alfa. Each ml of concentrate contains 2 mg sebelipase alfa. Each 

vial contains 20 mg of sebelipase alfa in 10 ml.  
- The other ingredients are sodium citrate (see section 2 under ‘KANUMA contains sodium’), citric 

acid monohydrate, human serum albumin, and water for injections.  
 

What KANUMA looks like and contents of the pack 
KANUMA is supplied as a concentrate for solution for infusion (sterile concentrate). It is a solution that 
is clear to slightly opalescent, and colourless to slightly coloured.  
 
Pack size: 1 vial containing 10 ml of concentrate. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder 
Alexion Europe SAS 
103-105 rue Anatole France 
92300 Levallois-Perret 

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


30 

France 
 
Manufacturer: 
Almac Pharma Services 
Seagoe Industrial Estate 
Craigavon BT63 5UA 
United Kingdom 
 
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. 
 
--------------------------------------------------------------------------------------------------------------------------- 
The following information is intended for healthcare professionals only: 
 
 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
Each vial of KANUMA is intended for single use only. KANUMA has to be diluted with sodium chloride 
9 mg/ml (0.9%) solution for infusion using aseptic technique.  
The diluted solution should be administered to patients using a low-protein binding infusion set equipped 
with an in-line, low-protein binding 0.2 μm filter, with a surface area of greater than 4.5 cm2 as available 
in order to avoid filter occlusion.   
 
Preparation of the sebelipase alfa infusion  
 
KANUMA should be prepared and used according to the following steps. Aseptic technique should be 
used. 
a. The number of vials to be diluted for infusion should be determined based on the patient’s weight 

and prescribed dose. 
b. It is recommended to allow KANUMA vials to reach a temperature between 15 °C and 25 °C prior 

to dilution to minimise the potential for the formation of sebelipase alfa protein particles in 
solution. The vials should not be left outside the refrigerator longer than 24 hours prior to dilution 
for infusion. The vials should not be frozen, heated or microwaved and should be protected from 
light. 

c. The vials should not be shaken. Prior to dilution, the concentrate in the vials should be inspected 
visually; the concentrate should be clear to slightly opalescent, colourless to slightly coloured 
(yellow). Due to the proteinaceous nature of the medicinal product, slight flocculation (e.g., thin 
translucent fibres) may be present in the vial concentrate and is acceptable for use. 

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


31 

d. Do not use if the concentrate is cloudy, or if foreign particulate matter is present. 
e. Up to 10 ml of concentrate should be slowly withdrawn from each vial and diluted with sodium 

chloride 9 mg/ml (0.9%) solution for infusion. See table 1 for recommended total infusion volumes 
by weight range. The solution should be mixed gently, and not be shaken. 

 
Table 1: Recommended infusion volumes (1 mg/kg dose)* 

Weight range (kg) Total infusion volume (ml) 
1-10 10 

11-24 25 
25-49 50 
50-99 100 

100-120 250 
* The infusion volume should be based on the prescribed dose and should be prepared to a final 
sebelipase alfa concentration of 0.1-1.5 mg/ml. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 


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