Affymax, Inc. (Nasdaq:AFFY) and Takeda Pharmaceuticals U.S.A., Inc. (TPUSA) today announced the presentation of post-hoc sub-group analyses of the EMERALD Phase 3 studies that evaluated OMONTYS ® (peginesatide) Injection, an erythropoiesis-stimulating agent (ESA), for the treatment of anemia due to chronic kidney disease (CKD) in adult dialysis patients. The analyses, which explore intravenous (IV) iron utilization in U.S. patients in the EMERALD Phase 3 studies, were presented in an oral session at the 2012 American Society of Nephrology (ASN) Kidney Week meeting. In these exploratory post-hoc analyses, investigators pooled data on IV iron dose, along with measures of iron deficiency -- serum ferritin and transferrin saturation (TSAT), from U.S. patients enrolled in the EMERALD 1 and 2 studies (approximately 80 percent of study population). In the full analysis population (randomized patients receiving ≥1 study drug dose; n=853 OMONTYS, n=436 epoetin) over a 60-week period, patients in the OMONTYS group received an average of 148.8 mg of IV iron per month and patients in the epoetin group received 168.5 mg per month. In the completer population (≥60 weeks’ drug exposure; ferritin, TSAT measured at same visit; n=604 OMONTYS; n=336 epoetin), patients in the OMONTYS group received an average of 152.9 mg per month and patients in the epoetin group received an average of 171.8 mg per month. TSAT at baseline was 30.2% and 29.4% in the OMONTYS and epoetin groups, respectively. Beginning at the first time point (week 12), TSAT for the full analysis population was 37.9% and 30.7% for OMONTYS and epoetin, respectively, and TSAT for the completer analysis population was 37.9% and 30.9% for OMONTYS and epoetin, respectively. Serum ferritin levels at baseline were 686 ng/mL and 674 ng/mL in the OMONTYS and epoetin groups, respectively. At week 60, serum ferritin levels for the full analysis population were 742 ng/mL and 768 ng/mL in the OMONTYS and epoetin groups, respectively, and serum ferritin levels for the completer analysis population were 733 ng/mL and 752 ng/mL in the OMONTYS and epoetin groups, respectively. The clinical significance of these analyses is unknown.
“Anemia management is multi-faceted and given the interdependence of irons and ESAs in red blood cell production, it’s important to evaluate utilization of these agents in dialysis patients who are being treated for the condition,” said Robert Provenzano, MD, Chair, Division of Nephrology, St. John Hospital & Medical Center, Detroit, and presenter of these EMERALD analyses. “The observations of these post-hoc analyses from the EMERALD studies may warrant further scientific evaluation.”According to the OMONTYS prescribing information, healthcare professionals should correct or exclude other causes of anemia, including iron deficiency, before initiating treatment. The majority of patients with CKD will require supplemental iron during the course of ESA therapy. Evaluate transferrin saturation and serum ferritin prior to and during treatment, and administer supplemental iron when serum ferritin is less than 100 mcg/L or when serum ferritin saturation is less than 20%. For lack or loss of response to OMONTYS, initiate a search for causative factors, including iron deficiency. Please see full prescribing information, available at www.omontys.com. About the EMERALD Studies Evaluating approximately 1,600 dialysis patients across 172 sites in the U.S. and Europe, the primary efficacy endpoint of the EMERALD 1 and 2 studies was a mean change in Hb between the baseline and evaluation period (between weeks 29 through 36) following study entry. In these trials, CKD patients on dialysis who were stable on epoetin were randomized to receive OMONTYS either once monthly or to continue treatment with epoetin (according to its labeling), with dose adjustments to maintain Hb levels within the study-specified range (between 10.0-12.0 g/dL). Current Prescribing Information recommends reducing or interrupting the dose as Hb levels approach or exceed 11 g/dL. The EMERALD studies were part of the first Phase 3 program to prospectively evaluate the cardiovascular (CV) safety of different ESAs based on a composite cardiovascular safety endpoint (CSE). The CSE was adjudicated by a blinded and independent committee.
About Anemia Due to CKD in Adult Patients on DialysisAnemia is a common complication in CKD patients on dialysis because their kidneys are unable to produce erythropoietin, the hormone responsible for red blood cell production. Since adequate iron levels are needed for the production of red blood cells and hemoglobin, treatment guidelines recommend iron is used in conjunction with erythropoiesis-stimulating agents (ESAs) in treating anemia in dialysis patients. As of 2010, the United States Renal Data System noted there were 410,000 people in the United States who were on dialysis. About OMONTYS OMONTYS ® (peginesatide) Injection is a synthetic, pegylated, peptide-based ESA, and its building blocks (amino acids) are arranged in a different order than erythropoietin (i.e., it has no sequence homology to endogenous erythropoietin). On March 27, 2012, the FDA approved OMONTYS (dosed once-monthly) for the treatment of anemia due to CKD in adult patients on dialysis. Indication and Limitations of Use OMONTYS® (peginesatide) Injection is indicated for the treatment of anemia due to chronic kidney disease (CKD) in adult patients on dialysis. OMONTYS is not indicated and is not recommended for use in patients with CKD not on dialysis, in patients receiving treatment for cancer and whose anemia is not due to CKD, or as a substitute for red blood cell (RBC) transfusions in patients who require immediate correction of anemia. OMONTYS has not been shown to improve symptoms, physical functioning, or health-related quality of life. IMPORTANT SAFETY INFORMATION WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE. Chronic Kidney Disease:
- In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL.
- No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks.
- Use the lowest OMONTYS dose sufficient to reduce the need for RBC transfusions.
Warnings and PrecautionsIncreased mortality, myocardial infarction, stroke, and thromboembolism:
- Using ESAs to target a hemoglobin level of greater than 11 g/dL increases the risk of serious adverse cardiovascular reactions and has not been shown to provide additional benefit. Use caution in patients with coexistent cardiovascular disease and stroke. Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality. A rate of hemoglobin rise of >1 g/dL over 2 weeks may contribute to these risks.
- In controlled clinical trials of ESAs in patients with cancer, increased risk for death and serious adverse cardiovascular reactions including myocardial infarction and stroke was observed.
- There is increased mortality and/or increased risk of tumor progression or recurrence in patients with cancer receiving ESAs.
- In controlled clinical trials of ESAs, ESAs increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and deep venous thrombosis (DVT) in patients undergoing orthopedic procedures.
- In 2 trials of OMONTYS, patients with CKD not on dialysis experienced increased specific cardiovascular events.
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