IgG antibodies to Fabrazyme were purified from 15 patients with high antibody titers (≥ 12,800) and studied for inhibition of in vitro enzyme activity.  Under the conditions of this assay, most of these 15 patients had inhibition of in vitro enzyme activity ranging between 21-74% at one or more time points during the study.  Assessment of inhibition of enzyme uptake in cells has not been performed.  No general pattern was seen in individual patient reactivity over time.  The clinical significance of binding and/or inhibitory antibodies to Fabrazyme is not known.  In patients followed in the open-label extension study, reduction of GL-3 in plasma and GL-3 inclusions in superficial skin capillaries was maintained after antibody formation. 

As with all therapeutic proteins, there is potential for immunogenicity.  The data reflect the percentage of patients whose test results were considered positive for antibodies to Fabrazyme using an ELISA and radioimmunoprecipitation (RIP) assay for antibodies. The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.  For these reasons, comparison of the incidence of antibodies to Fabrazyme with the incidence of antibodies to other products may be misleading.

Testing for IgE antibodies was performed in approximately 60 patients in clinical trials who experienced moderate to severe infusion reactions or in whom mast cell activation was suspected.  Seven of these patients tested positive for Fabrazyme-specific IgE antibodies or had a positive skin test to Fabrazyme.  Patients who have had a positive skin test to Fabrazyme, or who have tested positive for Fabrazyme-specific IgE antibodies in clinical trials with Fabrazyme have been re-challenged [see Clinical Studies (14) , Warnings and Precautions (5.4) and Dosage and Administration (2) ].

The following adverse reactions have been identified during post approval use of FABRAZYME. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

In postmarketing experience with agalsidase beta, severe and serious infusion-related reactions have been reported, some of which were life-threatening, including anaphylactic shock [see Warnings and Precautions (5.1) ].   Reactions have included localized angioedema (including auricular swelling, eye swelling, dysphagia, lip swelling, edema, pharyngeal edema, face swelling, and swollen tongue), generalized urticaria, bronchospasm, and hypotension.

Adverse reactions (regardless of relationship) resulting in death reported in the postmarketing setting with FABRAZYME treatment included cardiorespiratory arrest, respiratory failure, cardiac failure, sepsis, cerebrovascular accident, myocardial infarction, renal failure, and pneumonia. Some of these reactions were reported in Fabry disease patients with significant underlying di