Think Fabrazyme first for females with Fabry: Start with Trusted Therapy Today
Females with Fabry have been historically undertreated1,2
In the multicenter female Fabry study (n=224):3
of females were
untreated
even though criteria for treatment initiation were fulfilled
- Elevated plasma lyso-GL-3 levels in treatment-naive females can be a marker of disease burden. These women showed a higher frequency of pain than women ~8 years older with normal lyso-GL-3
- Mapping disease progression over time can help you identify a decline in organ function
In the Fabry registry (n=1077):4,*
Only 47% of females with CKD > Stage 3 are treated vs 88% of males
CKD=chronic kidney disease.
*Data as of January 2007 including 1077 women enrolled in the Fabry Registry.
Females with Fabry disease are not just “carriers”5
How a mosaic develops with x-inactivation6
X-inactivation can lead to females with Fabry having a range of symptoms.7
- Females who do not present with classical early signs still might be at risk for severe complications in specific organ systems7
- Females can have near-normal levels of α-GAL A in plasma and leukocytes, and still present with clinical manifestations due to random X-inactivation in tissues7
Females with Fabry can suffer from life-altering symptoms
Females with Fabry have higher occurrence of serious complications than females in the general population:4
End-stage renal disease4,8
White matter lesions11,12
Stroke/transient ischemic attack9,10
Left ventricular hypertrophy13,14
In the Fabry Registry, ~70% of females reported having signs and symptoms.*4
45%
Have abdominal pain15
43%
Have neuropathic pain4
39%
Have diarrhea15
39%
Have proteinuria4
(≥300 mg/day)
*Data as of January 2007, including 1077 women enrolled in the Fabry Registry.
Neuropathic pain could be a red flag suggesting underlying organ damage.15
Fabry is progressive, and ERT should be considered upon early signs of disease in females16,17
- Don’t wait until she’s had her first stroke or has severe CKD
- When you map disease progression over time and see decline in organ function, start Fabrazyme for appropriate patients
Think Fabrazyme first, think decreased occurrence of severe clinical events in female patients18
Occurrence of severe clinical events (death, stroke, renal and cardiac events) in female patients with Fabry disease decreased after the first 6 months of treatment with Fabrazyme18
Incidence of clinical events in female patients treated with Fabrazyme
Ortiz A, et al. J Med Genet. 2016;53(7):495-502.
- Overall, 14% of the 403 females in the study experienced a total of 57 events within 5 years of Fabrazyme initiation
- Highest incidence rate of events seen in the first 6 months of treatment
- Rates decreased with longer exposure to Fabrazyme and stabilized over time
- Cardiac and renal events were the most common, followed by stroke and death
For context, in a study on the natural history of Fabry disease prior to the initiation of ERT, in a population of 168 females, 35% (n=59) experienced cardiac events and 12% (n=20) experienced a cerebrovascular event over a median of 12 years.19
“I’ve learned it's very important as a woman to take care of yourself first. I know that goes against our instincts as mothers, but if you aren't well, it's a lot harder to take care of your family.”
Marie, a real Fabrazyme patient for over 20 years
IMPORTANT SAFETY INFORMATION
IMPORTANT SAFETY INFORMATION
|
WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate FABRAZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g. anaphylaxis) occurs, discontinue FABRAZYME and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1)]. |
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions Including Anaphylaxis
In clinical trials and post-marketing experience, approximately 1% of patients developed anaphylactic or severe hypersensitivity reactions, some life-threatening, during Fabrazyme infusion. 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. Consider pretreating with antihistamines, antipyretics, and/or corticosteroids; however, reactions may still occur.
In Fabrazyme clinical trials, 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 those with high antibody titers compared with antibody negative adult patients.
- 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 Fabrazyme clinical trials, 59% of patients experienced infusion-associated reactions (IARs), some of which were severe. IARs are defined as those occurring on the same day as the infusion. The incidence of these reactions was higher in patients who were positive for anti-Fabrazyme antibodies than those negative for anti-Fabrazyme antibodies.
- Consider pretreatment with antipyretics, antihistamines, and/or corticosteroids to reduce the risk of IARs; however, they may still occur.
- If a mild or moderate IAR occurs, consider holding the infusion temporarily, decreasing the infusion rate, and/or reducing the Fabrazyme dosage. If a severe IAR occurs, discontinue Fabrazyme immediately and initiate appropriate medical treatment as needed. Assess the risks and benefits of readministering Fabrazyme and monitor patients closely if readministering.
- Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from IARs. Closely monitor patients with compromised cardiac function receiving Fabrazyme.
Common Adverse Reactions
Adverse reactions reported (≥20%) were upper respiratory tract infection, chills, pyrexia, headache, cough, paresthesia, fatigue, peripheral edema, dizziness, and rash.
Please see full Prescribing Information, including Boxed WARNING
IMPORTANT SAFETY INFORMATION
Show moreIMPORTANT SAFETY INFORMATION
|
WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate FABRAZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g. anaphylaxis) occurs, discontinue FABRAZYME and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1)]. |
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions Including Anaphylaxis
In clinical trials and post-marketing experience, approximately 1% of patients developed anaphylactic or severe hypersensitivity reactions, some life-threatening, during Fabrazyme infusion. 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. Consider pretreating with antihistamines, antipyretics, and/or corticosteroids; however, reactions may still occur.
In Fabrazyme clinical trials, 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 those with high antibody titers compared with antibody negative adult patients.
- 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 Fabrazyme clinical trials, 59% of patients experienced infusion-associated reactions (IARs), some of which were severe. IARs are defined as those occurring on the same day as the infusion. The incidence of these reactions was higher in patients who were positive for anti-Fabrazyme antibodies than those negative for anti-Fabrazyme antibodies.
- Consider pretreatment with antipyretics, antihistamines, and/or corticosteroids to reduce the risk of IARs; however, they may still occur.
- If a mild or moderate IAR occurs, consider holding the infusion temporarily, decreasing the infusion rate, and/or reducing the Fabrazyme dosage. If a severe IAR occurs, discontinue Fabrazyme immediately and initiate appropriate medical treatment as needed. Assess the risks and benefits of readministering Fabrazyme and monitor patients closely if readministering.
- Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from IARs. Closely monitor patients with compromised cardiac function receiving Fabrazyme.
Common Adverse Reactions
Adverse reactions reported (≥20%) were upper respiratory tract infection, chills, pyrexia, headache, cough, paresthesia, fatigue, peripheral edema, dizziness, and rash.
Please see full Prescribing Information, including Boxed WARNING
INDICATION AND USAGE
Fabrazyme® is indicated for the treatment of adult and pediatric patients 2 years of age and older with confirmed Fabry disease.
References: 1. Germain DP, Arad M, Burlina A, et al. Mol Genet Metab. 2019;126(3):224-235. 2. Wanner C, Feldt-Rasmussen U, Jovanovic A, et al. ESC Heart Failure. 2020;7:825-834. 3. Lenders M, Hennermann JB, Kurschat C, et al. Orphanet J Rare Dis. 2016; 11:88:1-11. 4. Wilcox WR. Mol Genet Metab. 2008;93(2):112-128. 5. Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30. 6. Willard HF. The sex chromosomes and X chromosome inactivation. In: Valle D, Beaudet AL, Vogelstein B, et al, eds. The Online Metabolic and Molecular Bases of Inherited Disease; McGraw Hill; 2014. 7. Guffon N. J Med Genet. 2003;40(4):e38. 8. 2017 USRDS Annual Data Report. United States Renal Data System website. https://usrds. org/annual-data-report/previousadrs. Accessed June 2022. 9. MacDermot KD, Holmes A, Miners AH. J Med Gen. 2001;38(11):769-775. 10. Benjamin EJ, Blaha MJ, Chiuve SE, et al. Circulation. 2017;135(10):e146-e603. 11. Fellgiebel A, Muller MJ, Ginsberg L. Lancet Neurol. 2006;5(9):791-795. 12. Burlina A, Politei J. J Inborn Error Metab Screen. 2016;4:1-7. doi:10.1177/2326409816661361. 13. Linhart A, Kampmann C, Zamorano JL, et al; European FOS Investigators. Eur Heart J. 2007;28(10):1228-1235. 14. Schirmer H, Lunde P, Rasmussen K. Eur Heart J. 1999;20(6):429-438. 15. Wilcox WR, Feldt-Rasmussen U, Martins AM, et al. Mol Genet Metab. 2018;28:45-51. 16. Biegstraaten M, Arngrímsson R, Hollak CEM. et al. Orphanet J Rare Dis. 2015;10:36. 17. Ortiz A, Germain DP, Desnick RJ, et al. Mol Genet Metab. 2018;123(4):416-427. 18. Ortiz A, et al. J Med Genet. 2016;53(7):495-502. 19. Schiffman R, Warnock DG, Banikazemi M, et al. Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy. Nephrol Dial Transplant. 2009;24(7):2102–2111.