Profile
Cerezyme® has demonstrated long-term efficacy, and established safety profiles with 20 years of real-world experience in the treatment of Gaucher disease1–5
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Demonstrated efficacy in visceral and haematological parameters5,6
Demonstrated efficacy in certain bone parameters7–10
Demonstrated efficacy in children treated globally*11–14
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Individualised dosing for optimal response1,2
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Established safety profile1-5
*The Cerezyme® treatment group from the Gaucher Registry studies represents patients who received either Ceredase (alglucerase) or Cerezyme® initially and continued treatment with Cerezyme® long term.4,5,11,12,14,15,16
Evidence
The Gaucher Registry is the world’s largest cooperative observational database for Gaucher disease, providing data on more than 6,000 patients worldwide.16 Data from the Gaucher Registry is used to assess the effectiveness of treatment for symptoms commonly experienced by patients with Gaucher disease such as splenomegaly, thrombocytopenia, hepatomegaly and bone pain.3,4,9,12,16
Visceral and haematological parameters
Cerezyme® has shown both early and long-term improvements in visceral and haematological parameters5,6
In a 9 month, non-inferiority, phase 3 study, Cerezyme® demonstrated improvements from baseline:6
47.1% reduction in spleen volume with Cerezyme® from baseline
21.4% reduction in liver volume with Cerezyme® from baseline
25.4 g/dL increase in haemoglobin with Cerezyme® from baseline
43.5% increase in platelet count with Cerezyme® from baseline
In a 10 year retrospective study involving 757 patients, those treated with Cerezyme® showed:5
73% reduction in spleen volume vs. baseline (19.4±16.2 multiples of normal (MN) vs. 5.2±3.6 MN; p<0.0001; n=107)
44% reduction in liver volume vs. baseline (1.8±0.8 MN vs. 1.0±0.2 MN; p<0.0001; n=105)
2.4 g/dL increase in haemoglobin level vs. baseline (11.2±1.7 g/dL vs. 13.6±1.6 g/dL; p<0.0001; n=376)
75% increase in platelet count vs. baseline (95.3±52.8 x 103/mm3 vs. 166.66±59.7 x 103/mm3; p<0.0001; n=397)
Bone health
Skeletal complications of Gaucher disease are progressive and therefore, early initiation of Cerezyme® could improve bone outcomes for patients.10
Bone involvement is the principal cause of pain, disability and reduced quality of life in Gaucher disease patients of all ages.17 The pathophysiology responsible for bone involvement in Gaucher disease is not completely understood.17
Gaucher disease affects the bone marrow and mineralised components of bone, causing:17
Bone pain and bone crisis - bone marrow infiltration and plasma cell dyscrasias
Reduced bone mineral density (BMD) - modelling and remodelling abnormalities of bones, resulting in developmental changes, loss of bone mineral (osteopenia/osteoporosis), cortical thinning, lytic lesions, and fragility fractures
Increased risk of avascular necrosis (AVN) - a major, irreversible complication of type 1 Gaucher disease and can lead to joint destruction, the need for joint replacement surgery, and chronic disability.10
Cerezyme® decreases the occurrence of bone pain and bone crisis vs. baseline7,9
Cerezyme® significantly decreased the number of patients reporting bone pain and bone crises vs. baseline5
Cerezyme® improved BMD within 12 months vs. baseline7
Patients on Cerezyme® achieved near-normal BMD after 8 years8
The impact of Cerezyme® on long-term improvements in BMD was dose-related8
Initiation of Cerezyme® within 2 years of diagnosis was shown to significantly reduce the risk of AVN, compared with treatment initiated at least 2 years after diagnosis10
Paediatric patients
Cerezyme® improved visceral, haematological, certain bone parameters, and normalised growth and puberty vs. baseline11–14
Published paediatric data for type 1 patients from the Gaucher Registry demonstrated:
Cerezyme® significantly reduced spleen and liver volumes in children vs. baseline11,12
Cerezyme® significantly improved haematological parameters in children vs. baseline11,12
Cerezyme® can normalise growth in children with Gaucher disease and result in catch-up growth during treatment (relative to pre-treatment height)11,12
Cerezyme® increased BMD in the lumbar spine vs. baseline11,12
Cerezyme® reduced or eliminated bone crisis in children during the study duration, compared to before treatment initiation11,12
Cerezyme® resulted in effective amelioration of osteopenia in children and adolescents vs. baseline12
Cerezyme® reduced or eliminated bone pain and improved bone lesions in children within 26 months vs. baseline13
Cerezyme® normalised growth and time of puberty onset in most patients14
In bone and growth studies, the Cerezyme® treatment group from the Gaucher Registry studies represents patients who received either alglucerase or imiglucerase initially and continued treatment with imiglucerase long term.5,10–12,15
Mechanism of action
Cerezyme® is a modified form of the enzyme β-glucocerebrosidase which reduces the accumulation of glucosylceramide (GL-1). Cerezyme® is an enzyme replacement therapy (ERT) with demonstrated long-term efficacy, an established safety profile and real-world experience in the treatment of Gaucher disease.1,3,4
Cerezyme® reduces the build-up of GL-1 because the modified form of the enzyme, β-glucocerebrosidase, breaks down GL-1 into glucose and ceramide. By replacing the missing enzyme, Cerezyme® can reduce the accumulation of GL-1 in patients with non-neuronopathic (type 1) or chronic neuronopathic (type 3) Gaucher disease who exhibit clinically significant non-neurological manifestations of the disease.1
Since 1991, The Gaucher Registry has collected voluntary information from over 6,000 people internationally.2 Data from the Registry sponsored by Sanofi Genzyme is used to help researchers and physicians understand the impact of Gaucher disease and the effectiveness of long-term treatment.
Usage
Cerezyme administration
Cerezyme® treatment should be individualised for each patient and disease management should be directed by physicians knowledgeable in the treatment of Gaucher disease.1
Initial doses of 60 U/kg of body weight once every 2 weeks have shown improvement in haematological and visceral parameters within 6 months of therapy and continued use has either stopped progression of or improved bone disease. Administration of doses as low as 15 U/kg of body weight once every 2 weeks has been shown to improve haematological parameters and organomegaly, but not bone parameters.
No dose adjustment is necessary for the paediatric population.
At initial infusions, Cerezyme® should be administered at a rate not exceeding 0.5 unit per kg body weight per minute, i.e. 120 min for a patient whose dose is 60 U/kg, whatever the patient’s weight.
Maximum infusion rate is 1 unit per kg body weight per minute, i.e. 60 min for a patient whose dose is 60 U/kg, whatever the patient’s weight.
Infusions should be administered every 2 weeks.
Initially treatment should be administered in a clinical setting. Infusion of Cerezyme® at home may be considered for patients who are tolerating their infusions well for several months. Self-infusion at home also requires training of the patient or caregiver by a healthcare professional in a clinical setting.
Initial infusion rate should not exceed 0.5 unit/kg/min. At subsequent infusions, infusion rate may be increased. Patients experiencing adverse events during the infusion need to immediately stop the infusion process and seek the attention of a healthcare professional.
Initial doses of 60 U/kg of body weight once every 2 weeks have shown improvement in haematological and visceral parameters within 6 months of therapy and continued use has either stopped progression of or improved bone disease. Administration of doses as low as 15 U/kg of body weight once every 2 weeks has been shown to improve haematological parameters and organomegaly, but not bone parameters.
No dose adjustment is necessary for the paediatric population.
At initial infusions, Cerezyme® should be administered at a rate not exceeding 0.5 unit per kg body weight per minute, i.e. 120 min for a patient whose dose is 60 U/kg, whatever the patient’s weight.
Maximum infusion rate is 1 unit per kg body weight per minute, i.e. 60 min for a patient whose dose is 60 U/kg, whatever the patient’s weight.
Infusions should be administered every 2 weeks.
Initially treatment should be administered in a clinical setting. Infusion of Cerezyme® at home may be considered for patients who are tolerating their infusions well for several months. Self-infusion at home also requires training of the patient or caregiver by a healthcare professional in a clinical setting.
Initial infusion rate should not exceed 0.5 unit/kg/min. At subsequent infusions, infusion rate may be increased. Patients experiencing adverse events during the infusion need to immediately stop the infusion process and seek the attention of a healthcare professional.
Adverse Reactions
Adverse reactions are listed by system organ class and frequency in the table below. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.1
| MedDRA system organ class | Common (≥1/100 to <1/10) | Uncommon (≥1/1,000 to <1/100) | Rare (≥1/10,000 to <1/1,000) |
|---|---|---|---|
| Nervous system disorders | Dizziness, headache, paraesthesia* | ||
| Cardiac disorders | Tachycardia*, cyanosis* | ||
| Vascular disorders | Flushing*, hypotension* | ||
| Respiratory, thoracic and mediastinal disorders | Dyspnoea*, coughing* | ||
| Gastrointestinal disorders | Vomiting, nausea, abdominal cramping, diarrhoea | ||
| Immune system disorders | Hypersensitivity reactions | Anaphylactoid reactions | |
| Skin and subcutaneous tissue disorders | Urticaria/angioedema*, pruritus*, rash* |
| |
| Musculoskeletal and connective tissue disorders | Arthralgia, backache* | ||
| General disorders and administration site conditions | Infusion site discomfort, infusion site burning, infusion site swelling, injection site sterile abscess, chest discomfort*, fever, rigors, fatigue |
Symptoms suggestive of hypersensitivity (*marked in the table above) have been noted, overall in approximately 3% of the patients. Onset of such symptoms has occurred during or shortly after infusions. These symptoms generally respond to treatment with antihistamines and/or corticosteroids. Patients should be advised to discontinue infusion of the product and contact their physician if these symptoms occur.
During the first year of treatment, immunoglobulin G antibodies to Cerezyme® may form in approximately 15% of patients. Patients with antibodies to Cerezyme® have a higher risk of hypersensitivity reactions.
Limited experience from 150 pregnancy outcomes suggests that Cerezyme® is beneficial in controlling the underlying Gaucher disease during pregnancy. Risk-benefit treatment assessment is required for each pregnancy. Consult section 4.6 of SmPC.
References
- Cerezyme® summary of product characteristics.
- Abrams R, Kaddi CD, Tao M, et al. CPT Pharmacometrics Syst. Pharmacol. 2020 9, 374–383.
- Serratrice C, Carballo S, Serratrice J, et al. Core Evid. 2016;11:37–47.
- Mistry PK et al. Am J Hematol. 2017;92(9):929–939.
- Weinreb NJ, Goldblatt J, Villalobos J, et al. J Inherit Metab Dis. 2013;36(3):543–553.
- Grabowski GA, Barton NW, Pastores G, et al. Ann Intern Med. 1995;122(1):33–39.
- Sims K, Pastores G, Weinreb N, et al. Clin Genet. 2008;73(5):430–440.
- Wenstrup RJ, Kacena KA, Kaplan P, et al. J Bone Miner Res. 2007;22(1):119–126.
- Charrow J, Dulisse B, Grabowski GA, et al. Clin Genet. 2007;71(3):205–211.
- Mistry PK, Deegan P, Vellodi A, et al. Br J Haematol. 2009;147(4):561–570.
- Andersson H, Kaplan P, Kacena K, et al. Pediatrics. 2008;122(6):1182–1190.
- Mistry PK, Weinreb NJ, Kaplan P, et al. Blood Cells Mol Dis. 2011;46(1):66–72.
- El-Beshlawy A, Ragab L, Youssry I, et al. J Inherit Metab Dis.2006;29(1):92–98.
- Kauli R, Zaizov R, Lazar L, et al. Isr Med Assoc J. 2000;2(2):158–163.
- El-Beshlawy A, Tylki-Szymanska A, Vellodi A, et al. Mol Genet Metab. 2017;120(1–2):47–56.
- Weinreb NJ, Kaplan P. Am J Haematol. 2015;90(S1):S2–S5.
- Hughes D, Mikosch P, Belmatoug N, et al. J Bone Miner Res. 2019;34(6):996–1013.
MAT-XU-2204065 (v3.0) Date of preparation: October 2023