PRESS RELEASE: Ortho Biotech Reiterates Confidence in PROCRIT Safety and Efficacy When Used According to Label

Gaithersburg, MD (September 11, 2007) – As the Food and Drug Administration (FDA) Cardiovascular and Renal Drugs Advisory Committee (CRDAC) and Drug Safety and Risk Management Advisory Committee (DSRMAC) meet today to discuss questions related to erythropoiesis-stimulating agents (ESA’s), Ortho Biotech reiterates its position on the following key issues that will be discussed:

• The studies being examined by the FDA Advisory Committees evaluated hemoglobin targets above 13 grams per deciliter of blood (g/dL). In March 2007, label guidance for all ESAs was revised to reflect a maximum hemoglobin of 12 g/dL. When patients are treated according to the label, PROCRIT® (Epoetin alfa) is a safe and effective therapeutic option in the management of anemia in patients with chronic renal failure (CRF). 

• The weight of clinical evidence suggests that patients experience the greatest benefit from a hemoglobin of between 10 -12 g/dL, and that patients who fall below a hemoglobin of 10 g/dL experience greater morbidity and mortality, and are more likely to require a blood transfusion.

• The company agrees that additional data are needed to determine how to best identify and treat "ESA hyporesponders," or those patients who do not respond adequately to ESA therapy.
  

PROCRIT® represents a revolutionary treatment option in anemia management. ESAs, including PROCRIT®, continue to be the only viable alternative to blood transfusions for the treatment of anemia in CRF patients. ESAs provide clear clinical benefit in CRF patients with regard to transfusion avoidance and improvements in physician-assessed and patient-reported outcomes. The benefits and risks of PROCRIT® have been established in well-controlled clinical trials and observed in clinical experience over the past 18 years in four million patients worldwide across approved indications. 

Ortho Biotech looks forward to working closely with the FDA to help ensure that healthcare professionals have the information they need to continue to use PROCRIT® safely and effectively.

About PROCRIT® (Epoetin alfa)

PROCRIT® can be used for the treatment of anemia in patients with most types of cancer receiving chemotherapy, with chronic renal failure who are on dialysis and those who are not on dialysis, who are being treated with zidovudine for HIV infection, and to reduce the need for transfusion in anemic patients who are scheduled for elective noncardiac, nonvascular surgery. Depending on the country in which Epoetin alfa is marketed, these indications may differ.

Important U.S. Safety Information for PROCRIT®

From the Boxed Warnings

• Use the lowest dose of PROCRIT® that will gradually increase the hemoglobin (Hb) concentration to the lowest level sufficient to avoid the need for red blood cell (RBC) transfusion.

• PROCRIT® and other erythropoiesis-stimulating agents (ESAs) increased the risk for death and for serious cardiovascular events (including serious arterial and venous thromboembolic events, myocardial infarction, stroke, congestive heart failure) when administered to target a Hb of greater than 12 g/dL. A rate of hemoglobin rise of greater than 1 g/dL over 2 weeks may also contribute to these risks.
  

• Cancer patients: Use of ESAs:
  • Shortened the time to tumor progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target a Hb of greater than 12 g/dL.
  • Shortened overall survival and increased deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy when administered to target a Hb of greater than 12 g/dL.
  • Increased the risk of death when administered to target a Hb of 12 g/dL in patients with active malignant disease receiving neither chemotherapy nor radiation therapy. ESAs are not indicated for this population.

• Patients receiving PROCRIT® pre-operatively for reduction of allogeneic RBC transfusions: A higher incidence of deep venous thrombosis was documented in patients receiving PROCRIT® who were not receiving prophylactic anticoagulation. Antithrombotic prophylaxis should be strongly considered when PROCRIT® is used to reduce allogeneic RBC transfusions.
  

Contraindications

PROCRIT® is contraindicated in patients with uncontrolled hypertension or with known hypersensitivity to albumin (human) or mammalian cell-derived products.

Additional Important Safety Information

• Monitor Hb regularly during therapy, more frequently following a dosage adjustment or until Hb becomes stable.
• Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients with chronic renal failure receiving PROCRIT® by subcutaneous administration. If any patient develops a sudden loss of response to PROCRIT®, accompanied by severe anemia and low reticulocyte count, and anti-erythropoietin antibody-associated anemia is suspected, withhold PROCRIT® and other erythropoietic proteins. Contact ORTHO BIOTECH (1-888-2ASKOBI or 1-888-227-5624) to perform assays for binding and neutralizing antibodies. If erythropoietin antibody-mediated anemia is confirmed, PROCRIT® should be permanently discontinued and patients should not be switched to other erythropoietic proteins.

• The safety and efficacy of PROCRIT® therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (eg, sickle cell anemia, myelodysplastic syndromes, or hypercoagulable disorders).
• In some female patients, menses have resumed following PROCRIT® therapy; the possibility of pregnancy should be discussed and the need for contraception evaluated.
• Prior to and regularly during PROCRIT® therapy monitor iron status; transferrin saturation should be ≥ 20% and ferritin should be ≥ 100 ng/mL. During therapy absolute or functional iron deficiency may develop and all patients will eventually require supplemental iron to adequately support erythropoiesis stimulated by PROCRIT®.
• In studies, the most common side effects included fever (pyrexia), diarrhea, nausea, vomiting, swelling of hands or feet (edema), lack or loss of strength or weakness (asthenia, fatigue), shortness of breath, high blood pressure, headache, joint pain (arthralgias), abnormal skin sensations (as tingling or tickling or itching or burning; paresthesia), rash, constipation, and upper respiratory infection.
  

Please visit www.procrit.com for the full Prescribing Information, including the Boxed Warning.

About Ortho Biotech Products, L.P.

Ortho Biotech Products, L.P. is a leading biopharmaceutical company devoted to helping improve the lives of patients with cancer and with anemia due to multiple causes, including chronic kidney disease. Since it was founded in 1990, Ortho Biotech and its worldwide affiliates have earned a global reputation for researching, manufacturing and marketing innovative products that enhance patients' health. Located in Bridgewater, NJ, Ortho Biotech is an established market leader in Epoetin alfa therapy for anemia management. The company also markets treatments for recurrent ovarian cancer, rejection of transplanted organs and other serious illnesses. For more information, visit www.orthobiotech.com.