Proven Viral Safety

• No albumin added to final formulation^26,27*
• No evidence of viral transmission ever reported
  with ReFacto ^21,24
• Purification process designed for viral safety²⁷
  • Includes a high-affinity anti–factor VIII monoclonal antibody step and 4 additional chromatography steps²⁷
  • Also includes solvent-detergent treatment step designed to inactivate all known lipid-enveloped viruses²⁷
• ALL recombinant factor VIII products undergo murine monoclonal antibody (MAb) immunoaffinity chromatography during the purification process^16-20

*The Chinese hamster ovary cell line used to produce ReFacto is grown in culture medium that contains human serum albumin; no albumin is added during purification or in final formulation. Following purification, the albumin concentration is below the detection limit of the assay.

Proven Tolerability Incidence of inhibitor formation similar to that reported for other factor VIII therapies Clinical evidence suggests that factor VIII products show similar rates of inhibitor development among previously treated patients (PTPs).22,23,28-31,43 No head-to-head clinical studies have been conducted. High-titer inhibitor development in PTPs is uncommon, with inhibitor formation reported in 0% to 2.9% of PTPs in separate noncomparative clinical trials of recombinant factor VIII products22,23,28-31,43 In a pivotal clinical trial, 1 of 113 PTPs developed an inhibitor22,23 32 of 101 previously untreated patients (PUPs) developed an inhibitor22,23 Of the patients who developed inhibitors, 25 underwent immune tolerance therapy (ITT) By the end of the study, inhibitors resolved in 20 of those patients receiving ITT Low titer inhibitors are common in PUPs and in PTPs on factor VIII products, as are high titer inhibitors in PUPs. High titer inhibitors, which are generally rare in PTPs, have been reported postmarketing in PTPs on ReFacto. Indication ReFacto is indicated for the control and prevention of hemorrhagic episodes and for surgical prophylaxis and for short-term routine prophylaxis to reduce the frequency of spontaneous bleeding episodes in patients with hemophilia A. The effect of regular routine prophylaxis on long-term morbidity and mortality is unknown. Important Safety Information • As with the intravenous administration of any protein product, adverse reactions may include headache, fever, chills, flushing, nausea, vomiting, tiredness, or symptoms of allergic reactions. • The remote possibility exists for hypersensitivity to non-human mammalian proteins. Known hypersensitivity to mouse or hamster proteins may be a contraindication to the use of ReFacto. • Allergic reactions such as hives, itching, difficulty breathing, rapid heart rate, light-headedness and anaphylaxis have been reported for all factor VIII products. Patients should discontinue use of the product and contact their health care provider immediately and/or seek emergency care if any of these symptoms occur. Please see ReFacto Prescribing Information The health information contained herein is provided for educational purposes only and is not meant to replace personal discussions between health care providers and patients. All decisions about patient care must be made with a health care provider who can assess the special needs of each individual patient.