TREATMENT YOU CAN TRUST
Choose the proven therapy for Fabry disease with over 18 years of experience.1
MECHANISM OF ACTION
FABRAZYME CAN BE USED REGARDLESS OF GENOTYPE OR DISEASE SEVERITY.1
FABRAZYME: For patients with any level of enzyme activity.1
Fabrazyme is a fully functional enzyme, with an amino acid sequence identical to the body’s own native enzyme.1 Fabrazyme binds to a natural receptor on the cell surface, allowing it to be internalized.2 Once inside the cell, Fabrazyme is directly transported to the lysosome.1,2 In the lysosome, Fabrazyme hydrolyzes globotriaosylceramide (GL -3), resulting in clearance of accumulated GL-3 in major organs.1
WATCH THIS VIDEO TO LEARN HOW FABRAZYME WORKS TO CLEAR GL-3.
CONSIDER FABRAZYME FIRST
CLINICAL STUDIES
PIVOTAL STUDY RESULTS
FABRAZYME was proven to clear GL-3 in as quickly as 5 months in the capillary endothelium of the kidney, heart, and skin.1
Study 1: At 5 months, a GL-3 inclusion score of 0 was achieved in the capillary endothelium of the: Kidney 20 (69%) Fabrazyme patients compared with 0 (0%) placebo patients; Heart: 21 (72%) Fabrazyme patients compared with 1 (3%) placebo patient; Skin: 29 (100%) Fabrazyme patients compared with 1 (3%) placebo patient.1
Study 1 open-label extension: At 6 months, the majority of patients treated with Fabrazyme had a GL-3 inclusion score of 0 in the capillary endothelium of the kidney, heart, and skin.1
*Study 1: Randomized, 1:1, double-blind, placebo-controlled study. 58 patients with Fabry disease (56 males, 2 females), 16 to 61 years, all naive to enzyme replacement therapy (ERT). Patients received either 1 mg/kg of Fabrazyme or placebo every 2 weeks for 5 months. GL-3 inclusions were graded on a scale of 0 (trace or nearly none) to 3 (severe). All 58 patients in Study 1 participated in the Study 1 extension, a 54-month, open-label, extension trial.1
Placebo patients began Fabrazyme treatment at entry into the open-label extension. This graph represents pooled results from all patients in the study (Fz/Fz and PI/Fz).1
EXTENSION STUDY RESULTS
FABRAZYME rapidly normalized plasma GL-3 and maintained it for up to 5 years.1,8
Similar long-term responses were seen in a majority of patients, with sustained GL-3 clearance in the capillary endothelium of the kidney (8/8) and heart (6/8) at 4.5 years.1
FABRAZYME WAS EVALUATED FOR OUTCOMES IN CLINICALLY SIGNIFICANT EVENTS.*
A smaller percentage of patients in the FABRAZYME treatment group experienced a clinically significant event.1
HAD RENAL, CARDIAC, CEREBROVASCULAR EVENTS, OR DEATH*
(HR† 0.57, 95% CI: 0.27, 1.22, P=0.14)
Study design: A randomized, double-blind, placebo-controlled, multinational, multicenter study of 82 patients (72 males and 10 females) with Fabry disease, all naive to enzyme replacement therapy. Patients were randomly assigned to Fabrazyme 1 mg/kg or placebo every 2 weeks for up to 35 months (median follow up 18.5 months).
The primary efficacy endpoint was the time to first occurrence of a clinically significant event (renal, cardiac, or cerebrovascular event, or death).
The study included patients aged 20 to 72 years (median age: 45), with a baseline median plasma αGAL level of 1.5 nmol/hour/mL (range: 0 to 1.5). Patients included had advanced Fabry disease with mild-to-moderate kidney dysfunction at baseline (median eGFR of 52 mL/min/1.73m2 [range: 25 to 113]).1
FABRAZYME IN PEDIATRIC POPULATIONS.
The overall efficacy and safety profile of FABRAZYME in pediatric patients was consistent with that seen in adults.1
- This pediatric study evaluated 16 pediatric patients with Fabry disease (14 males, 2 females), aged 8 to 16 years (median 12 years)1
- In 14 male patients, Fabrazyme normalized plasma GL-3 levels at 24 weeks and sustained levels at 48 weeks1
- The two female patients’ plasma GL-3 levels remained normal through week 481
- 12 of the 14 males had GL-3 inclusions at baseline, and all 12 male patients achieved GL-3 inclusion scores of 0 at 24 and 48 weeks of treatment1
Study Design: Open-label, single-arm, multinational, multicenter study in 16 pediatric patients with Fabry disease (14 males, 2 females), aged 8 to 16 years (median 12 years). Histological evaluation of the capillary endothelium, deep vessel endothelium, deep vessel smooth muscle cells, and perineurium of biopsied skin was conducted using histochemistry with light microscopy. Scoring was on a scale of 0 (defined as none) to 3 (severe).
Study Dose: Fabrazyme 1 mg/kg every 2 weeks for up to 48 weeks.
Baseline Characteristics: All 14 males had elevated plasma GL-3 levels (i.e., >7.03μg/mL), whereas the two female patients had normal plasma GL-3 levels. 12 of the 14 males had GL-3 inclusions present on skin biopsy (scores 1, 2, or 3), whereas the two females had no GL-3 inclusions at baseline.1
FABRAZYME is the ONLY ERT indicated for patients 2 years of age and older.1
- In an analysis of 24 Fabrazyme-treated pediatric patients with Fabry disease aged 2 to <8 years, plasma GL-3 levels were normalized1
- At baseline, all male patients had elevated plasma GL-3 (i.e., >7.03 μg/mL)
- After treatment, plasma GL-3 levels fell within the normal range (i.e., ≤7.03 μg/mL) in 90.9% (20/22), 94.7% (18/19), and 92.3% (12/13) of patients at 6, 12, and 24 months, respectively1
THE RATE OF KIDNEY FUNCTION DECLINE WAS STUDIED IN FABRAZYME-TREATED PATIENTS.
Long-term observational study results show a difference in the mean eGFR slope between the FABRAZYME-treated and untreated-patients.1*
Study design: In a long-term observational study, the rate of decline in renal function (eGFR slope) was assessed in patients with Fabry disease age ≥16 years, treated with Fabrazyme (n=122) and matched to a historical cohort of untreated patients (n=122). In the matched cohort, 72% of patients were male and 28% were female. The median baseline eGFR was 93 mL/min/1.73m2/year.1
ESTIMATED DIFFERENCE IN MEAN SLOPE OF eGFR
(95% CI: 0.5, 3.0)1
|
|
Fabrazyme-treated group |
Untreated group |
|
The mean slopes of eGFR of the 2 groups were1: |
1.5mL/min/ |
-3.2mL/min/ |
|
The median follow-up time was1: |
3 years |
4.5 years |
|
Maximum follow-up time was 5 years in both groups1 |
||
TRUST IN THE WELL-ESTABLISHED SAFETY PROFILE OF FABRAZYME
The safety of FABRAZYME has been assessed in 4 clinical trials involving 162 patients with over 473 patient-years of experience.1,9
SUMMARY OF ADVERSE REACTIONS1
- In clinical trials and postmarketing safety experience with Fabrazyme, approximately 1% of patients developed anaphylactic or severe hypersensitivity reactions during Fabrazyme infusion
- In clinical trials with Fabrazyme, 59% of patients experienced infusion-associated reactions, some of which were severe. Infusion-associated reactions are defined as adverse reactions occurring on the same day as the infusion
- In patients experiencing infusion-associated reactions, pretreatment with an antipyretic and antihistamine is recommended. Infusion-associated reactions occurred in some patients after receiving pretreatment
- Higher incidences of hypersensitivity reactions were observed in adult patients with persistent anti-Fabrazyme antibodies and in adult patients with high antibody titer compared to that in antibody negative adult patients
- Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from infusion-associated reactions. These patients should be monitored closely if Fabrazyme is administered
- Most common adverse reactions (≥20%) are: upper respiratory tract infection, chills, pyrexia, headache, cough, paresthesia, fatigue, peripheral edema, dizziness, and rash
- To report SUSPECTED ADVERSE REACTIONS, contact Genzyme at 1-800-745-4447 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
SUMMARY OF COMMON ADVERSE REACTIONS IN CLINICAL TRIALS (STUDIES 1 AND 2).1
Occurring in at least 5% of FABRAZYME-treated patients at an incidence >2.5% compared with placebo-treated patients.1
|
Adverse Reaction |
FABRAZYME |
Placebo |
|
Upper respiratory tract infectiona |
53 |
42 |
|
Chillsb |
49 |
13 |
| Pyrexia | 39 | 22 |
|
Headache |
39 |
28 |
|
Cough |
33 |
25 |
|
Paresthesia |
31 | 18 |
|
Fatigue |
24 |
17 |
|
Peripheral edema |
21 | 7 |
|
Dizziness |
21 | 8 |
|
Rash |
20 |
10 |
|
Pain in extremity |
19 | 8 |
|
Myalgiac |
18 | 7 |
|
Lower respiratory tract infection |
18 | 7 |
|
Pain |
16 | 13 |
|
Back pain |
16 | 10 |
|
Hypertension |
14 | 5 |
|
Adverse Reaction |
FABRAZYME |
Placebo |
| Pruritus |
10 |
3 |
|
Tachycardia |
9 | 3 |
|
Excoriation |
9 | 2 |
|
Increased blood creatinine |
9 |
5 |
|
Tinnitus |
8 |
3 |
|
Dyspnea |
8 |
2 |
|
Fall |
6 |
3 |
|
Burning sensation |
6 |
0 |
|
Anxiety |
6 |
3 |
|
Depression |
6 |
2 |
|
Wheezing |
6 |
0 |
|
Hypoacusis |
5 |
0 |
|
Chest discomfort |
5 |
2 |
|
Fungal infection |
5 |
0 |
|
Viral infection |
5 | 0 |
|
Hot flush |
5 | 0 |
a Includes reports of upper respiratory infection, nasal congestion, sinusitis, respiratory tract congestion, and pharyngitis.
b Includes reports of chills and feeling cold.
c Includes reports of myalgia and muscle spasms.
ADMINISTRATION
COUNT ON OPTIONS
FABRAZYME can be administered in multiple treatment settings.
PHYSICIAN OFFICES
INFUSION CENTERS
HOME
Choice of treatment setting is at the discretion of the physician. Because of the potential for severe infusion-associated reactions, appropriate medical support measures should be readily available.
DOSING AND ADMINISTRATION.
The recommended dosage of Fabrazyme is 1 mg/kg body weight infused every 2 weeks as an intravenous (IV) infusion.1
For step-by-step instructions on how to calculate dose, preparation for use, storage and handling, and administering Fabrazyme, download the
Fabrazyme Preparation & Administration Info Sheet.
WATCH THIS TUTORIAL VIDEO TO LEARN MORE ABOUT ADMINISTERING FABRAZYME.
SUPPORT FOR YOUR PATIENTS
Sanofi offers dedicated support and assistance for patients and families affected by Fabry disease.
REQUEST A REP OR ATTEND AN EDUCATIONAL PROGRAM
Connect with a representative to learn more, or sign up for invitations to upcoming educational programs.
IMPORTANT SAFETY INFORMATION
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Anaphylaxis and Hypersensitivity Reactions
In clinical trials and postmarketing safety experience with Fabrazyme, approximately 1% of patients developed anaphylactic or severe hypersensitivity reactions during Fabrazyme infusion. Life-threatening anaphylactic and severe hypersensitivity reactions have been observed in patients during Fabrazyme infusions.
- Reactions have included localized angioedema (including swelling of the face, mouth, and throat), bronchospasm, hypotension, generalized urticaria, dysphagia, rash, dyspnea, flushing, chest discomfort, pruritus, and nasal congestion.
- Interventions have included cardiopulmonary resuscitation, oxygen supplementation, IV fluids, hospitalization, and treatment with inhaled beta-adrenergic agonists, antihistamines, epinephrine, and IV corticosteroids.
- If anaphylactic or severe hypersensitivity reactions occur, immediately discontinue administration of Fabrazyme and provide necessary emergency treatment. Because of the potential for severe hypersensitivity reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.
In clinical trials with Fabrazyme, some patients developed IgE antibodies or skin test reactivity specific to Fabrazyme.
- Higher incidences of hypersensitivity reactions were observed in adult patients with persistent anti-Fabrazyme antibodies and in adult patients with high antibody titer compared to that in antibody negative adult patients.
- Physicians should consider testing for IgE antibodies in patients who experienced suspected hypersensitivity reactions and consider the risks and benefits of continued treatment in patients with anti-Fabrazyme IgE antibodies. Rechallenge of these patients should only occur under the direct supervision of qualified personnel, with appropriate medical support measures readily available.
Infusion-Associated Reactions
In clinical trials with Fabrazyme, 59% of patients experienced infusion-associated reactions, some of which were severe. Infusion-associated reactions are defined as adverse reactions occurring on the same day as the infusion. The incidence of infusion-associated reactions was higher in patients who were positive for anti-Fabrazyme antibodies than in patients who were negative for anti-Fabrazyme antibodies.
- In patients experiencing infusion-associated reactions, pretreatment with an antipyretic and antihistamine is recommended. Infusion-associated reactions occurred in some patients after receiving pretreatment.
- If an infusion-associated reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administrating additional antipyretics, antihistamines, and/or steroids may ameliorate the symptoms.
- If severe infusion-associated reactions occur, immediate discontinuation of the administration of Fabrazyme should be considered, and appropriate medical treatment should be initiated. Severe reactions are generally managed with administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen when clinically indicated. Because of the potential for severe infusion-associated reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.
- Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from infusion-associated reactions. Monitor closely patients with compromised cardiac function if Fabrazyme is administered to these patients
ADVERSE REACTIONS
- Common adverse reactions reported (≥20% and >2.5% compared to placebo) were upper respiratory tract infection (53% vs 42%), chills (49% vs 13%), pyrexia (39% vs 22%), headache (39% vs 28%), cough (33% vs 25%), paresthesia (31% vs 18%), fatigue (24% vs 17%), peripheral edema (21% vs 7%), dizziness (21% vs 8%), and rash (20% vs 10%).
INDICATION AND USAGE
Fabrazyme® is indicated for the treatment of adult and pediatric patients 2 years of age and older with confirmed Fabry disease.
Please see full Prescribing Information for Fabrazyme.
References: 1. Fabrazyme prescribing information. Cambridge, MA. Genzyme Corporation; 2021. 2. Prabakaran T, Nielsen R, Larsen JV. PLOS ONE. 2011;6(9):e25065. 3. Data on file. Based on publicly available patient numbers as of December 2023. 4. Germain et al. J Med Genet 2015;52(5): 353-358. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413801/pdf/jmedgenet-2014- 102797.pdf. 5. Banikazemi M, Bultas J, Waldek S, et al; for the Fabry Disease Clinical Trial Study Group. Ann Intern Med.2007;146:77-86. [Epub 16 January 2007].doi:10.7326/0003- 4819-146-2-200701160-00148. https:/www. acpjournals.org/ doi/epdf10.7326/0003-4819- 146-2-200701160-00148. 6. Patient Support - Patient Services. Sanofi. Accessed 6 Dec 2022. https://www.sanofi.us/ en/products -and-resources/patient-services. 7. Germain DP, Waldek S, Banikazemi M, et al. J Am Soc Nephrol. 2007;18:1547 -1557. 8. Eng CM, Guffon N, Wilcox WR, et al. N Engl J Med. 2001;345(1):9-16. 9. Data on file. Genzyme Corporation.
IMPORTANT SAFETY INFORMATION
Show moreIMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Anaphylaxis and Hypersensitivity Reactions
In clinical trials and postmarketing safety experience with Fabrazyme, approximately 1% of patients developed anaphylactic or severe hypersensitivity reactions during Fabrazyme infusion. Life-threatening anaphylactic and severe hypersensitivity reactions have been observed in patients during Fabrazyme infusions.
- Reactions have included localized angioedema (including swelling of the face, mouth, and throat), bronchospasm, hypotension, generalized urticaria, dysphagia, rash, dyspnea, flushing, chest discomfort, pruritus, and nasal congestion.
- Interventions have included cardiopulmonary resuscitation, oxygen supplementation, IV fluids, hospitalization, and treatment with inhaled beta-adrenergic agonists, antihistamines, epinephrine, and IV corticosteroids.
- If anaphylactic or severe hypersensitivity reactions occur, immediately discontinue administration of Fabrazyme and provide necessary emergency treatment. Because of the potential for severe hypersensitivity reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.
In clinical trials with Fabrazyme, some patients developed IgE antibodies or skin test reactivity specific to Fabrazyme.
- Higher incidences of hypersensitivity reactions were observed in adult patients with persistent anti-Fabrazyme antibodies and in adult patients with high antibody titer compared to that in antibody negative adult patients.
- Physicians should consider testing for IgE antibodies in patients who experienced suspected hypersensitivity reactions and consider the risks and benefits of continued treatment in patients with anti-Fabrazyme IgE antibodies. Rechallenge of these patients should only occur under the direct supervision of qualified personnel, with appropriate medical support measures readily available.
Infusion-Associated Reactions
In clinical trials with Fabrazyme, 59% of patients experienced infusion-associated reactions, some of which were severe. Infusion-associated reactions are defined as adverse reactions occurring on the same day as the infusion. The incidence of infusion-associated reactions was higher in patients who were positive for anti-Fabrazyme antibodies than in patients who were negative for anti-Fabrazyme antibodies.
- In patients experiencing infusion-associated reactions, pretreatment with an antipyretic and antihistamine is recommended. Infusion-associated reactions occurred in some patients after receiving pretreatment.
- If an infusion-associated reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administrating additional antipyretics, antihistamines, and/or steroids may ameliorate the symptoms.
- If severe infusion-associated reactions occur, immediate discontinuation of the administration of Fabrazyme should be considered, and appropriate medical treatment should be initiated. Severe reactions are generally managed with administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen when clinically indicated. Because of the potential for severe infusion-associated reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.
- Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from infusion-associated reactions. Monitor closely patients with compromised cardiac function if Fabrazyme is administered to these patients
ADVERSE REACTIONS
- Common adverse reactions reported (≥20% and >2.5% compared to placebo) were upper respiratory tract infection (53% vs 42%), chills (49% vs 13%), pyrexia (39% vs 22%), headache (39% vs 28%), cough (33% vs 25%), paresthesia (31% vs 18%), fatigue (24% vs 17%), peripheral edema (21% vs 7%), dizziness (21% vs 8%), and rash (20% vs 10%).
INDICATION AND USAGE
Fabrazyme® is indicated for the treatment of adult and pediatric patients 2 years of age and older with confirmed Fabry disease.
Please see full Prescribing Information for Fabrazyme.
References: 1. Fabrazyme prescribing information. Cambridge, MA. Genzyme Corporation; 2021. 2. Prabakaran T, Nielsen R, Larsen JV. PLOS ONE. 2011;6(9):e25065. 3. Data on file. Based on publicly available patient numbers as of December 2023. 4. Germain et al. J Med Genet 2015;52(5): 353-358. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413801/pdf/jmedgenet-2014- 102797.pdf. 5. Banikazemi M, Bultas J, Waldek S, et al; for the Fabry Disease Clinical Trial Study Group. Ann Intern Med.2007;146:77-86. [Epub 16 January 2007].doi:10.7326/0003- 4819-146-2-200701160-00148. https:/www. acpjournals.org/ doi/epdf10.7326/0003-4819- 146-2-200701160-00148. 6. Patient Support - Patient Services. Sanofi. Accessed 6 Dec 2022. https://www.sanofi.us/ en/products -and-resources/patient-services. 7. Germain DP, Waldek S, Banikazemi M, et al. J Am Soc Nephrol. 2007;18:1547 -1557. 8. Eng CM, Guffon N, Wilcox WR, et al. N Engl J Med. 2001;345(1):9-16. 9. Data on file. Genzyme Corporation.