The most serious infusion-related adverse reactions reported with ELAPRASE were anaphylactic and allergic reactions (see BOXED WARNING and WARNINGS).

In clinical studies, the most frequent serious adverse events related to the use of ELAPRASE were hypoxic episodes. Other notable serious adverse reactions that occurred in the ELAPRASE treated patients but not in the placebo patients included one case each of: cardiac arrhythmia, pulmonary embolism, cyanosis, respiratory failure, infection, and arthralgia.

Adverse reactions were commonly reported in association with infusions. The most common infusion-related reactions were headache, fever, cutaneous reactions (rash, pruritus, erythema, and urticaria), and hypertension. The frequency of infusion-related reactions decreased over time with continued ELAPRASE treatment.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a product cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in practice.

Table 3 enumerates those adverse reactions that were reported during the 53-week, placebo- controlled study that occurred in at least 10% of patients treated with ELAPRASE weekly administration, and that occurred more frequently than in the placebo patients. The most common ( > 30%) adverse reactions were pyrexia, headache, and arthralgia.

Table 3 Summary of Adverse Reactions Occurring in at Least 10% of Patients Treated with ELAPRASE Weekly in the 53-week Controlled Trial and Occurring More Frequently than in the Placebo Group

Immunogenicity

Fifty-one percent (32 of 63) of patients in the weekly ELAPRASE treatment arm in the clinical study (53-week placebo-controlled study with an open-label extension) developed anti-idursulfase IgG antibodies as assessed by ELISA or conformation specific antibody assay and confirmed by radioimmunoprecipitation assay (RIP). Sera from 4 out of 32 RIP confirmed anti-idursulfase antibody positive patients were found to neutralize idursulfase activity in vitro. The incidence of antibodies that inhibit cellular uptake of idursulfase into cells is currently unknown, and the incidence of IgE antibodies to idursulfase is not known. Patients who developed IgG antibodies at any time had an increased incidence of infusion reactions, including allergic reactions. The reduction of urinary GAG excretion was less in patients in whom circulating anti-idursulfase antibodies were detected. The relationship between the presence of anti-idursulfase antibodies and clinical efficacy outcomes is unknown.

The data reflect the percentage of patients whose test results were positive for antibodies to idursulfase in specific assays, and are highly dependent on the sensitivity and specificity of these assays. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to idursulfase with the incidence of antibodies to other products may be misleading.

No formal drug interaction studies have been conducted with ELAPRASE.

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