Ortho Biotech Modifies Prescribing Information for PROCRIT® (Epoetin alfa)

Label change based on data previously reported, communicated in late 2007

Bridgewater, NJ .– Ortho Biotech Products, L.P. today modified prescribing information for PROCRIT® (Epoetin alfa), following guidance from the U.S. Food and Drug Administration (FDA) to revise labeling for all drugs within the erythropoiesis-stimulating agent (ESA) class.

Modifications to the label were based on an unplanned interim analysis of Amgen’s PREPARE study in women with breast cancer receiving preoperative chemotherapy, and from GOG-191, a study of advanced cervical cancer patients conducted by the Gynecologic Oncology Group with support from Ortho Biotech. Both investigational studies were designed to evaluate the efficacy of maintaining hemoglobin levels greater than 12 grams per deciliter of blood (g/dL) and observed lower survival in patients being treated with ESAs. However, neither study showed a statistically significant effect on survival or tumor outcomes.

“These studies are consistent with results from previous studies demonstrating that ESAs should not be used to enhance the response to chemotherapy or radiotherapy, and should be administered to achieve a hemoglobin level of less than 12 g/dL,” said Craig Tendler, M.D., Vice President, Medical Affairs, Oncology/ Nephrology, Ortho Biotech Products, L.P. “We look forward to thoughtful consideration of the totality of available scientific evidence at next week’s FDA Oncologic Drugs Advisory Committee Meeting (ODAC), including a substantial body of data that has been submitted to the agency over the past several months.”

Ortho Biotech remains confident in the safety and efficacy of PROCRIT when used at the lowest dose to avoid transfusion in anemic patients receiving concomitant chemotherapy. The company also remains committed to continuing to work with the FDA to ensure that physicians have the most up-to-date information to support the most appropriate use of the product.

About PREPARE and GOG-191

PREPARE was a study in patients receiving neo-adjuvant breast cancer treatment in which darbepoetin alfa was administered to prevent anemia at target hemoglobin levels of 12.5-13 g/dL. After a median follow up of approximately three years, relapse-free survival (72% versus 78%), and overall survival (86% versus 90%), were lower in darbepoetin alfa-treated patients.

GOG-191 evaluated the efficacy of maintaining hemoglobin levels between 12-14 g/dL in patients with advanced cervical cancer undergoing chemotherapy or radiotherapy. Progression-free survival (59% versus 62%) at three years, and overall survival (61% versus 71%), were lower in Epoetin alfa-treated patients.

The Boxed Warnings have been modified to now read:

WARNINGS: Increased Mortality, Serious Cardiovascularand Thromboembolic Events, and Tumor Progression

Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.

Cancer:

* ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of 12 g/dL.
* The risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of 12 g/dL.
* To minimize these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions.
* Use only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
* Discontinue following the completion of a chemotherapy course.

Perisurgery: PROCRIT® increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.

(See WARNINGS: Increased Mortality, Serious Cardiovascular and Thromboembolic Events, WARNINGS: Increased Mortality and/or Tumor Progression, and DOSAGE AND ADMINISTRATION.)

Additional changes were made in the Warnings section of the label to reflect these two studies.

The company has worked closely with the FDA to ensure that the updated PROCRIT® label provides physicians and patients with the information they need to make the most appropriate and informed treatment decisions. To that end, Ortho Biotech is committed to disseminating this modified prescribing information through a “Dear Health Care Provider” letter, its product Web site and its product specialists.

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.

Important U.S. Safety Information for PROCRIT

Boxed WARNINGS: Increased Mortality, Serious Cardiovascular and Thromboembolic Events, and Tumor Progression

Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.

Cancer:

* ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of 12 g/dL.
* The risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of 12 g/dL.
* To minimize these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions.
* Use only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
* Discontinue following the completion of a chemotherapy course.

Perisurgery: PROCRIT® increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.

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

* The dose of PROCRIT® should be titrated for each patient to achieve and maintain the following hemoglobin levels:
o Chronic renal failure patients – hemoglobin levels between 10 to 12 g/dL. If a patient does not attain hemoglobin levels of 10 to 12 g/dL despite 12 weeks of appropriate PROCRIT® therapy, see DOSAGE and ADMINISTRATION in the PROCRIT Prescribing Information.
o Cancer or HIV patients – the lowest hemoglobin level sufficient to avoid transfusion and not to exceed 12 g/dL.
* Monitor hemoglobin regularly during therapy, more frequently following a dosage adjustment or until hemoglobin 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 (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.
* Prior to and regularly during PROCRIT® therapy monitor iron status; transferrin saturation should be 20% and ferritin should be ³ 100 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® .
* During PROCRIT® therapy, blood pressure should be monitored carefully and aggressively managed, particularly in patients with an underlying history of hypertension or cardiovascular disease.
* 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 WARNINGS.