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Data From Investigational Use of PROCRIT(R) (Epoetin alfa)

November 7, 2008
PHILADELPHIA, Nov. 7 /PRNewswire/ -- Data from an investigational, open-label, randomized study assessing extended dosing regimens of PROCRIT(R) (Epoetin alfa) in treating anemia in subjects with Stages 3 - 4 chronic kidney disease (CKD) were presented today at the American Society of Nephrology 41st Annual Meeting.

All three dosing groups, including the FDA-approved three-times-per-week (TIW) regimen, plus once-a-week (QW) and once-every-two-weeks (Q2W) investigational regimens, achieved a mean final hemoglobin (Hb) within the range of 11.0 - 11.9 g/dL. Based on the increases in Hb, the QW and Q2W investigational regimens were statistically non-inferior to the TIW regimen (lower limits of 95 percent confidence intervals [CIs] within the non-inferiority margin of -1 g/dL).

The percent of subjects with Hb exceeding 11.9 g/dL during the first 22 weeks of treatment was higher in the TIW group (86.2 percent) than in the QW (78.4 percent) and Q2W (71.2 percent) groups; the median per-subject frequency of Hb exceeding 11.9 g/dL was 6, 4 and 3 times for the TIW, QW and Q2W groups, respectively.

In the first 22 weeks of treatment, the proportion of subjects experiencing serious adverse events (SAEs) was 15 percent in the TIW group, compared with 22 percent in both the QW and Q2W groups. During the entire 44 weeks of treatment, the proportion of subjects experiencing SAEs was 29, 33 and 33 percent in the TIW, QW and Q2W groups, respectively. The number of subjects with investigator-confirmed thromboembolic vascular events (TVEs) over the first 22 weeks was 2 in the TIW, 2 in the QW and 3 in the Q2W groups; over 44 weeks, these numbers were 2, 5 and 8 in the TIW, QW and Q2W groups, respectively. The number of subjects who died during the first 22 weeks was 0 in the TIW, 6 in the QW and 3 in the Q2W groups. Over 44 weeks, 4, 6 and 4 subjects died, respectively. None of the deaths were considered related to the study drug.

"These data provide important insights into the potential use of extended-dosing regimens of Epoetin alfa in this patient population," said Pablo E. Pergola, M.D., Ph.D., Division of Nephrology, University of Texas Health Science Center and Renal Associates, P.A., San Antonio, Texas.

Study Design

In the study, 375 subjects averaging 70 years of age were randomized equally to one of the three dosing groups (TIW, QW and Q2W) and treated for 44 weeks. Subjects receiving PROCRIT TIW were switched to QW dosing after 22 weeks. A dose-adjustment algorithm was used to achieve a target Hb of 11.0 to 11.9 g/dL. The primary efficacy endpoint was change in Hb from baseline to the average of the last eight weeks of treatment through Week 22. Additional analyses were performed using data through Week 44.

The mean baseline estimated glomerular filtration rate was 30 mL/min/1.73 m2 and the median weekly EPO doses (IU) were 4,382, 4,364 and 6,091 for TIW, QW and Q2W groups, respectively. For the TIW, QW and Q2W groups, the mean baseline Hb was 9.6, 9.7 and 9.8 g/dL, respectively; the mean Hb increase was 1.8, 1.6 and 1.3 g/dL, respectively, and the mean final Hb was 11.4, 11.3 and 11.1 g/dL, respectively.

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 Safety Information

WARNINGS: Increased Mortality, Serious Cardiovascular and Thromboembolic Events, and increased risk of tumor progression OR recurrence

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 increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers (see WARNINGS: Table 1).

-- To decrease these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusion.

-- Use ESAs only for treatment of anemia due to concomitant myelosuppressive chemotherapy.

-- ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure.

-- Discontinue following the completion of a chemotherapy course.

Perisurgery: PROCRIT (Epoetin alfa) 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

-- 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 higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two 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.

-- Dose of PROCRIT

-- Chronic renal failure patients: The dose of PROCRIT should be titrated for each patient to achieve and maintain 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.

-- Cancer patients: PROCRIT therapy should not be initiated at hemoglobin levels greater than or equal to 10 g/dL. The dose of PROCRIT should be titrated for each patient to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for blood transfusion. Discontinue if after 8 weeks of therapy there is no response as measured by hemoglobin levels or if transfusions are still required (see recommended Dose Modification section in DOSAGE and ADMINISTRATION of the PROCRIT Prescribing Information).

-- HIV patients: The dose of PROCRIT should be titrated for each patient to achieve and maintain the lowest hemoglobin level sufficient to avoid transfusion and not to exceed the upper safety limit of 12 g/dL.

-- Monitor hemoglobin regularly during therapy, weekly 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 treated with PROCRIT; predominantly 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 greater than or equal to 20% and ferritin should be greater than or equal to 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.

-- Treatment of patients with grossly elevated serum erythropoietin levels (e.g., >200 mUnits/mL) is not recommended.

-- 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, and for the Medication Guide and Patient Instructions for Use.

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, N.J., 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

Source: Ortho Biotech Products, L.P.

CONTACT: Bill Foster, +1-908-541-4057, +1-908-392-6057 (cell), WFoster@its.jnj.com, for Ortho Biotech Products, L.P.

Web Site: http://www.orthobiotech.com/

http://www.procrit.com/



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