Treatment

Both symptom management and enzyme replacement therapy can play a role in the medical management of patients with Fabry disease. Like diagnosis, disease management usually requires a team approach among medical specialties, since Fabry disease affects many organ systems.

Enzyme replacement therapy addresses the enzyme deficiency in Fabry disease by providing an exogenous source of the deficient α-GAL enzyme. Fabrazyme^® (agalsidase beta) enzyme replacement therapy is indicated for use in patients with Fabry disease. Fabrazyme reduces globotriaosylceramide (GL-3) deposition in capillary endothelium of the kidney and certain other cell types. The reduction of GL-3 inclusions suggests that Fabrazyme may ameliorate disease expression; however, the relationship of GL-3 inclusion reduction to specific clinical manifestations of Fabry disease has not been established.

^{This image shows GL-3 accumulation in the kidney vascular endothelium before treatment with Fabrazyme.}

^{After treatment with Fabrazyme, GL-3 is reduced to normal or near normal levels.}

In a 2003 publication, a consensus panel comprised of physicians with expertise in treating Fabry disease recommended that enzyme replacement therapy be promptly initiated as early as possible in symptomatic patients. ^[1] Once treatment has begun, patients with Fabry disease should be followed carefully with regular physician visits to monitor renal and cardiac indicators of disease progression.

For more about the clinical trial record of Fabrazyme in reducing GL-3 inclusions, go to Clinical Studies Section.

Because Fabry disease is a progressive disease that may cause irreversible damage and in some cases life-threatening complications, early diagnosis is important. ^[1] For more about identifying Fabry disease in patients, go to Signs and Symptoms. Please note: The safety and effectiveness of Fabrazyme in pediatric patients have not been established.

To connect with physicians with experience in treating Fabry disease, contact Genzyme at 617-768-9000 or toll-free 800-745-4447, option 2.

Important Safety Information Fabrazyme (agalsidase beta) is indicated for use in patients with Fabry disease.  Fabrazyme reduces globotriaosylceramide (GL-3) deposition in capillary endothelium of the kidney and certain other cell types. The reduction of GL-3 inclusions suggests that Fabrazyme may ameliorate disease expression; however, the relationship of GL-3 inclusion reduction to specific clinical manifestations of Fabry disease has not been established. The most serious and most common adverse reactions reported with Fabrazyme are infusion reactions.  Serious and/or frequently occurring related adverse reactions consisted of one or more of the following events: chills, pyrexia, feeling hot or cold, dyspnea, nausea, flushing, headache, vomiting, paresthesia, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tightness, abdominal pain, dizziness, tachycardia, nasal congestion, diarrhea, edema peripheral, myalgia, back pain, pallor, bradycardia, urticaria, hypotension, face edema, rash, and somnolence. The occurrence of somnolence can be attributed to clinical trial specified pre-treatment with antihistamines.  Other reported serious adverse events included stroke, pain, ataxia, bradycardia, cardiac arrhythmia, cardiac arrest, decreased cardiac output, vertigo, hypoacousia, and nephrotic syndrome.  These adverse events also occur as manifestations of Fabry disease; an alteration in frequency or severity cannot be determined from the small numbers of patients studied. Infusion reactions occurred in many patients treated with Fabrazyme and some of the reactions were severe.  Patients should be given antipyretics prior to infusion.  Infusion reactions occurred in some patients after receiving pretreatment with antipyretics, antihistamines, and oral steroids.  Infusion reactions declined in frequency with continued use of Fabrazyme.  However, infusion reactions may still occur despite extended duration of Fabrazyme treatment.  Because of the potential for severe infusion reactions, appropriate medical support measures should be readily available when Fabrazyme is administered.  Patients with compromised cardiac function should be monitored closely if the decision is made to administer Fabrazyme. Most patients develop IgG antibodies to Fabrazyme.  A few patients developed IgE or skin test reactivity specific to Fabrazyme.  Physicians should consider testing for IgE in patients who experienced suspected allergic reactions and consider the risks and benefits of continued treatment in patients with anti- Fabrazyme IgE.   Patients with Fabrazyme- specific IgE antibody have been treated using a rechallenge protocol.  Rechallenge of these patients should only occur under the direct supervision of qualified personnel, with appropriate medical support measures readily available. The safety and efficacy in patients younger than 8 years of age have not been evaluated.  IgE immunologic responses in pediatric patients may differ from those in adults, as IgG seroconversion was associated with prolonged half-life concentrations of Fabrazyme, which is rarely observed in adult patients. Fabrazyme is available by prescription only. Side effects should be reported promptly to Genzyme Medical Information at 800-745-4447, option 2. To learn more, please see the full prescribing information (PDF) or contact Genzyme at 1-800-745-4447.

^References

1. Desnick RJ, Brady R, Barranger J, Collins AJ, Germain DP, Goldman M, Grabowski G, Packman S, Wilcox WR. Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 2003;138:338-346.