VPRIV SIDE EFFECTS

SIDE EFFECTS

Clinical Trials Experience

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

The data described below reflect exposure of 94 patients with type 1 Gaucher disease who received VPRIV at doses ranging from 15 Units/kg to 60 Units/kg every other week in 5 clinical studies. Fifty-four (54) patients were naive to enzyme replacement therapy (ERT) and received VPRIV for 9 months and 40 patients switched from imiglucerase to VPRIV treatment and received VPRIV for 12 months. Patients were between 4 and 71 years old at time of first treatment with VPRIV, and included 46 male and 48 female patients.

The most serious adverse reactions in patients treated with VPRIV were hypersensitivity reactions.

The most commonly reported adverse reactions (occurring in ≥10% of patients) that were considered related to VPRIV are shown in Table 1. The most common adverse reactions were hypersensitivity reactions.

Table 1: Adverse Reactions Observedin ≥ 10% of Adult and Pediatric Patients with Type 1 Gaucher Disease Treated with VPRIV in the Pooled 5 Clinical Studies

Less common adverse reactions affecting more than one patient (>2% in the treatment-naive group and > 3% in patients switched from imiglucerase to VPRIV treatment) were bone pain, tachycardia, rash, urticaria, flushing, hypertension, and hypotension.

Adverse Reactions In Pediatric Patients

The safety profile of VPRIV was similar between pediatric patients (ages 4 to 17 years) and adult patients. Adverse reactions more commonly seen in pediatric patients compared to adult patients include (>10% difference): rash, aPTT prolonged, and pyrexia.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection 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 VPRIV in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

In clinical studies, 1 of 54 (2%) enzyme treatment-naive patients treated with VPRIV developed IgG antibodies to VPRIV. One additional patient developed IgG antibodies to VPRIV during an extension study. In both patients, the IgG antibodies to VPRIV were determined to be neutralizing in an in vitro assay. The presence of IgG antibodies to VPRIV was not associated with hypersensitivity reactions. It is unknown if the presence of IgG antibodies to VPRIV is associated with a higher risk of infusion reactions. Patients with an immune response to other enzyme replacement therapies who are switching to VPRIV should continue to be monitored for antibodies to VPRIV.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of VPRIV. 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.

Gastrointestinal disorders: vomiting (in some cases vomiting can be serious, requiring hospitalization and/or drug discontinuation).

SRC: NLM .