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Observational Studies Assess the Potential Impact of LimitingErythropoiesis-Stimulating Agent Availability on Frequency of BloodTransfusions

CHICAGO, May 30, 2008 /PRNewswire/ -- Data from three observational studies reported at the American Society of Clinical Oncology (ASCO) Annual Meeting evaluated transfusion-related outcomes in cancer chemotherapy patients with various hemoglobin (Hb) levels prior to or during administration of erythropoiesis-stimulating agents (ESAs).

Two analyses were conducted using observational data from the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) Registry. The first study (Larholt et al., abstract number 6637) reported that lower mean Hb levels achieved during ESA therapy were associated with increased transfusion requirements in cancer patients receiving chemotherapy. Another study of oncology patients who initiated ESA therapy at different baseline Hb levels (Burton et al., publication number 20637) concluded that blood utilization was greater when ESA therapy was initiated in patients who had baseline Hb of less than 10 grams per deciliter of blood (g/dL) compared with patients who received ESA therapy with a baseline Hb between 10 and 11 g/dL.

The third study (Gilmore, et al., abstract number 6548) examined hematologic outcomes in ESA-treated cancer chemotherapy patients with chemotherapy-induced anemia before and after implementation of the Centers for Medicare and Medicaid Services (CMS) National Coverage Determination (NCD) for ESAs. The results found lower Hb values and higher transfusion rates in patients covered by Medicare following adoption of the NCD guidelines for reimbursement for ESA therapies.

"As ESA coverage policies have become more restrictive, these findings are important in helping stakeholders understand the potential impact on transfusion patterns. The data demonstrated that when patients achieved lower mean hemoglobin levels during ESA therapy for chemotherapy-induced anemia, the need for transfusions increased," said Kay Larholt, Sc.D., Vice President, Biometrics, at Abt Bio-Pharma Solutions, Inc., a biopharmaceutical research and consulting firm, and lead author of one of the analyses being presented.

About the Studies

In the Larholt et al. analysis, researchers reviewed observational data from an ongoing prospective registry of ESA-treated patients in 56 U.S. oncology clinics between December 2003 and April 2008, including data from hospital and community-based outpatient practices. Data were analyzed from 323 adult chemotherapy-treated oncology patients who had Hb concentrations less than 10 g/dL prior to ESA administration and received two or more ESA doses. Patients were categorized by mean achieved Hb levels (Hb 9.1 to 10 g/dL: n=117; Hb 10.1 to 11 g/dL: n=142; Hb 11.1 to 12 g/dL: n=64); the percent of patients transfused was 43%, 23% and 19% for each of the respective categories. The analysis suggested a difference (p < 0.01) in the percentage of patients transfused between levels of mean achieved Hb.

In the study conducted by Burton et al., data from 1,059 patients (ESA initiated Hb less than 10 g/dL: n=384, ESA initiated Hb 10 to 11 g/dL: n=675) from 59 sites included in the DOSE registry were analyzed. Researchers, who reviewed data from patients treated between December 2003 and November 2007, found that a greater proportion of patients received a transfusion when the baseline Hb was less than 10 g/dL (31%) than when the baseline Hb was between 10 and 11 g/dL (15%).

Gilmore et al. conducted a retrospective observational study of an electronic medical record database from a large oncology/hematology practice. They analyzed 401 Medicare cancer chemotherapy patients who had received two or more ESA doses. Study cohorts were defined based on the dates of ESA administration (pre-NCD cohort: January 1, 2007 through July 31, 2007; post- NCD cohort: August 1, 2007 through April 15, 2008). A total of 401 Medicare patients received ESAs for eight weeks (pre-NCD: n=243; post-NCD: n=158). The reported Hb levels were significantly higher in the pre-NCD cohort compared to the post-NCD cohort at each measured time point (mean Hb, g/dL, pre- vs. post- NCD: baseline, 10.7 vs. 9.7; four-week Hb, 11.0 vs. 10.2; eight-week Hb, 11.2 vs. 10.3). A greater proportion of patients required transfusion in the post- NCD cohort (pre-NCD 9.5 percent vs. post-NCD 18.4 percent).

Ortho Biotech Products, L.P. markets PROCRIT(R) (Epoetin alfa), an ESA.

About the DOSE Registry

The Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) Registry is an ongoing, prospective, observational registry collecting data on real-world practice patterns and outcomes in oncology patients treated with erythropoietic agents in U.S. community clinics and hospital centers. The registry provides outcomes data in oncology patients receiving chemotherapy from more than 80 sites across the United States.

About PROCRIT(R) (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.


    -- 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 greater than or equal to 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


    -- Discontinue following the completion of a chemotherapy course.

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


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:

       - 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.

       - 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 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.

    -- 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.

Posted: May 2008