Centocor Ortho Biotech Products, L.P. Statement on Prescribing Information Update for PROCRIT^® (Epoetin alfa)

Horsham, Pa., December 16, 2009 - Centocor Ortho Biotech Products, L.P. today announced it is updating the prescribing information for PROCRIT^® (Epoetin alfa) to include information in the BOXED WARNING and WARNINGS section about an increased risk of stroke in patients when erythropoiesis-stimulating agents (ESAs) are used to target hemoglobin levels of 13 g/dL and above.  This new safety information is based on results in patients with anemia, type 2 diabetes, and chronic renal failure (CRF) who were not on dialysis from a recent Amgen clinical study entitled, "TREAT: Trial to Reduce Cardiovascular Endpoints with Aranesp^® Therapy," and applies to all products in the ESA class of medicines.

The BOXED WARNING, Chronic Renal Failure section of the PROCRIT label has been revised and now reads:

Warnings: Increased Mortality, Serious Cardiovascular Events, Thromboembolic Events, Stroke and Increased Risk of Tumor Progression or Recurrence

Chronic Renal Failure:

• In clinical studies, patients experienced greater risks for death, serious cardiovascular events, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target hemoglobin levels of 13 g/dL and above.
• Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.

In addition, the WARNINGS section has been updated to include the following paragraph regarding the TREAT trial:

In a randomized, double-blind, placebo-controlled study of 4038 patients, there was an increased risk of stroke when darbepoetin alfa was administered to patients with anemia, type 2 diabetes, and CRF who were not on dialysis.  Patients were randomized to darbepoetin alfa treatment targeted to a hemoglobin level of 13 g/dL or to placebo.  Placebo patients received darbepoetin alfa only if their hemoglobin levels were less than 9 g/dL.  A total of 101 patients receiving darbepoetin alfa experienced stroke compared to 53 patients receiving placebo (5% vs. 2.6%; HR 1.92, 95% CI: 1.38, 2.68; p < 0.001).

Centocor Ortho Biotech Products, L.P. plans to communicate the potential risk to physicians through multiple channels.  Physicians are reminded to follow the general therapeutic guidelines in the Dosage and Administration section of the PROCRIT Prescribing Information and individually titrate doses in each patient to achieve and maintain hemoglobin levels between 10 and 12 g/dL.

About PROCRIT^® (Epoetin alfa)

PROCRIT is 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.

PROCRIT Nephrology Indication

• PROCRIT is indicated for the treatment of anemia associated with chronic renal failure, including patients on dialysis and patients not on dialysis. PROCRIT is indicated to elevate or maintain the red blood cell level (as manifested by the hematocrit or hemoglobin determinations) and to decrease the need for transfusions in these patients.

• Non-dialysis patients with symptomatic anemia considered for therapy should have a hemoglobin less than 10 g/dL.

• PROCRIT is not intended for patients who require immediate correction of severe anemia. PROCRIT may obviate the need for maintenance transfusions but is not a substitute for emergency transfusion.

• Prior to initiation of therapy, the patient's iron stores should be evaluated. Transferrin saturation should be at least 20% and ferritin at least 100 ng/mL. Blood pressure should be adequately controlled prior to initiation of PROCRIT therapy, and must be closely monitored and controlled during therapy.

Important Safety Information

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

• Patients with chronic renal failure experienced greater risks for death and serious cardiovascular events (including myocardial infarction, stroke, congestive heart failure, and hemodialysis vascular access thrombosis) when administered ESAs to target hemoglobin levels 13 g/dL and above in clinical studies; these risks also increased in controlled clinical trials of patients with cancer. A rate of hemoglobin rise of >1 g/dL over 2 weeks may contribute to these risks.
• Individually titrate to achieve and maintain hemoglobin levels between 10 to 12 g/dL.
• If the hemoglobin is increasing and approaching 12 g/dL, or increases by more than 1 g/dL in a 2-week period, the PROCRIT dose should be reduced by 25%. If the hemoglobin continues to increase, dose should be temporarily withheld until the hemoglobin begins to decrease, at which point therapy should be reinitiated at a dose 25% below the previous dose.
• Monitor hemoglobin regularly during therapy; twice a week for 2 to 6 weeks following a dosage adjustment until hemoglobin becomes stable.
• For patients whose hemoglobin does not attain 10 to 12 g/dL despite appropriate PROCRIT dose titrations over a 12-week period:

-     Do not use higher PROCRIT doses; use the lowest dose that will avoid the need for recurrent RBC transfusions,

-     Evaluate and treat for other causes of anemia:

1) Iron deficiency; 2) Underlying infectious, inflammatory, or malignant processes; 3) Occult blood loss; 4) Underlying hematologic diseases (i.e., thalassemia, refractory anemia, or other myelodysplastic disorders); 5) Vitamin deficiencies: Folic acid or vitamin B12; 6) Hemolysis; 7) Aluminum intoxication; 8) Osteitis fibrosa cystica; or 9) Pure Red Cell Aplasia (PRCA)

-      Thereafter, monitor hemoglobin and if responsiveness improves make dose adjustments according to the Prescribing Information (DOSAGE AND ADMINISTRATION); if responsiveness does not improve and the patient needs recurrent RBC transfusions discontinue PROCRIT.

• Hypertension and seizures were reported in controlled clinical trials involving PROCRIT and other ESAs. Blood pressure should be carefully monitored and aggressively managed.
• 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. PRCA has also been reported in patients receiving ESAs while undergoing treatment for hepatitis C with interferon and ribavirin. 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 Centocor Ortho Biotech (1-800-457-6399) 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 (e.g., 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.
• During therapy absolute or functional iron deficiency may develop and all patients will eventually require supplemental iron to adequately support erythropoiesis stimulated by PROCRIT.
• The most commonly reported side effects (>10%) in clinical trials were hypertension, headache, arthralgias, and nausea.

Please visit www.procrit.com for the full Prescribing Information, including the Boxed WARNINGS, and for the Medication Guide and Patient Instructions for Use.

Centocor Ortho Biotech redefines the standard of care in immunology, nephrology, and oncology.  Built upon a pioneering history, Centocor Ortho Biotech harnesses innovations in large-molecule and small-molecule research to create important new therapeutic options.  Beyond its innovative medicines, Centocor Ortho Biotech is at the forefront of developing education and public policy initiatives to ensure patients and their families, caregivers, advocates, and healthcare professionals have access to the latest treatment information, support services, and quality care. 

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