OBIZUR SIDE EFFECTS

SIDE EFFECTS

Common adverse reactions observed in greater than 5% of subjects in the clinical trial were development of inhibitors to porcine factor VIII.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction (AR) 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 clinical practice.

The safety and efficacy of OBIZUR was evaluated in a multi-center, prospective, open-label, clinical trial that investigated adult patients with acquired hemophilia A. Twenty-nine adult subjects were enrolled in the study, received at least one dose of OBIZUR and were evaluable for safety. Of the 29 adult subjects, 10 were between the ages of 40 and 65, and 19 were 65 years of age or older (18 Caucasian, 6 African-American, and 5 Asian). Ten (34%) subjects were female.

Immunogenicity

All subjects were monitored for development of inhibitory antibodies to OBIZUR using the Nijmegen modification of the Bethesda inhibitor assay. A subject was considered to have developed an OBIZUR inhibitor if the titer was ≥0.6 Bethesda Units (BU)/mL.

Of the 29 subjects treated with OBIZUR, 19 subjects were negative for anti-porcine factor VIII antibodies at baseline. Five of the 19 (26%) developed anti-porcine factor VIII antibodies following exposure to OBIZUR. Of the 10 subjects with detectable anti-porcine factor VIII antibodies at baseline, 2 (20%) experienced an increase in titer and eight (80%) experienced a decreasing to a non-detectable titer.

All subjects were also monitored for development of binding antibodies to baby hamster kidney (BHK) protein by a validated sequential ELISA (enzyme-linked immunosorbent assay). No patients developed de novo anti-BHK antibodies.

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 OBIZUR with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of OBIZUR. 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 product exposure.

• Immune system disorders: anamnestic reactions

SRC: NLM .