Affymax, Inc. (Nasdaq:AFFY) and Takeda Pharmaceuticals U.S.A., Inc. (TPUSA) today announced that pivotal Phase 3 data on the safety and efficacy of OMONTYS ® (peginesatide) Injection were published in the January 24 th issue the New England Journal of Medicine ( NEJM). These studies, known as EMERALD 1 and 2, compared OMONTYS given once monthly to epoetin administered one-to-three times per week (according to epoetin product labeling) in the treatment of anemia in adult chronic kidney disease (CKD) patients on hemodialysis. The EMERALD studies were part of the New Drug Application (NDA) upon which the U.S. Food and Drug Administration’s (FDA) March 27, 2012 approval of OMONTYS was based. These studies evaluated the use of the medication in treating one of the common complications of CKD among dialysis patients. OMONTYS is indicated for the treatment of anemia due to 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. Please see Important Safety Information including Boxed WARNINGS below. The efficacy and cardiovascular (CV) safety assessment data published in NEJM showed:
- Noninferiority to Epoetin in Maintenance of Hemoglobin (Hb): The difference between the OMONTYS and epoetin-treated groups in the mean change in Hb levels from baseline to the study evaluation period (calculated as the mean of all measurements during weeks 29-36) in EMERALD 1 and 2 was -0.15 g/dL (95 percent CI: -0.30, -0.01) and 0.10 g/dL (95 percent CI: -0.05, 0.26) respectively.
- Similar Cardiovascular Safety in Hemodialysis Population: In the EMERALD studies, 22.8 percent of OMONTYS patients experienced one of the composite cardiovascular events, compared to 24.4 percent of epoetin patients (hazard ratio for the cardiovascular composite safety endpoint was 0.95 (0.77, 1.17) (95 percent CI)). OMONTYS is not indicated in patients with CKD not on dialysis. These patients experienced increased specific cardiovascular events.
"The EMERALD results are important because they not only evaluated the efficacy of OMONTYS and epoetin; they also represent data from the first studies to prospectively compare the cardiovascular safety of different erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in dialysis patients with CKD,” said Steven Fishbane, M.D., Professor of Medicine, Hofstra North Shore-Long Island Jewish School of Medicine, lead author of the NEJM publication, and principal investigator for the EMERALD studies. “The EMERALD data demonstrated that OMONTYS administered once a month has a similar efficacy and cardiovascular safety profile when compared to epoetin administered one-to-three times weekly.”About the EMERALD Studies and Cardiovascular Safety Assessment Approximately 1,600 adult CKD hemodialysis patients across 178 sites in the U.S. and Europe were evaluated in the EMERALD 1 and 2 trials (1,066 patients received OMONTYS; 542 received epoetin). The primary efficacy endpoint of these studies was the mean change in Hb from the baseline Hb level to the mean level during the evaluation period (between weeks 29 through 36). In these trials, CKD patients on hemodialysis who were stable on epoetin, were randomized to receive OMONTYS either once every four weeks or to continue treatment with epoetin (according to epoetin labeling), with the dose adjusted as necessary to maintain Hb levels within the study-specified range (10.0-12.0 g/dL) for 52 weeks or more. 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 CV safety of different ESAs based on a composite cardiovascular safety endpoint (CSE). The CSE was adjudicated by a blinded and independent committee. Events included in the CSE pre-specified analysis were death from any cause, stroke, myocardial infarction, serious adverse events associated with congestive heart failure, unstable angina, or arrhythmia.
About Anemia Due to CKD in Adult Patients on DialysisAnemia is a complication of CKD and is associated with cardiovascular illness and mortality. As of 2010, the United States Renal Data System noted there were more than 410,000 people in the United States who were on dialysis. About OMONTYS ® (peginesatide) Injection OMONTYS is a synthetic, pegylated ESA. It is the only ESA that is peptide-based 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 United States Food and Drug Administration approved OMONTYS for the treatment of anemia due to CKD in adult patients on dialysis. The product is the first ESA to be marketed in the United States (U.S.) in over 10 years and is the only once-monthly ESA for anemia available to this patient population in the United States. 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.
- 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.
About Takeda Pharmaceuticals U.S.A., Inc. and Takeda Global Research & Development Center, Inc.Based in Deerfield, Ill., Takeda Pharmaceuticals U.S.A., Inc. and Takeda Global Research & Development Center, Inc. are subsidiaries of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. The respective companies currently market oral diabetes, insomnia, rheumatology, gastroenterology and cardiovascular disease treatments and seek to bring innovative products to patients through a pipeline that includes compounds in development for diabetes, gastroenterology, neurology and other conditions. To learn more about these Takeda companies, visit www.takeda.us. Takeda Forward-Looking Statement This press release contains forward-looking statements. Forward-looking statements include statements regarding Takeda's plans, outlook, strategies, results for the future, and other statements that are not descriptions of historical facts. Forward-looking statements may be identified by the use of forward-looking words such as "may," "believe," "will," "expect," "project," "estimate," "should," "anticipate," "plan," "assume," "continue," "seek," "pro forma," "potential," "target," "forecast," "guidance," "outlook" or "intend" or other similar words or expressions of the negative thereof. Forward-looking statements are based on estimates and assumptions made by management that are believed to be reasonable, though they are inherently uncertain and difficult to predict. Investors are cautioned not to unduly rely on such forward-looking statements. Forward-looking statements involve risks and uncertainties that could cause actual results or experience to differ materially from that expressed or implied by the forward-looking statements. Some of these risks and uncertainties include, but are not limited to, (1) the economic circumstances surrounding Takeda's business, including general economic conditions in Japan, the United States and worldwide; (2) competitive pressures and developments; (3) applicable laws and regulations; (4) the success or failure of product development programs; (5) actions of regulatory authorities and the timing thereof; (6) changes in exchange rates; (7) claims or concerns regarding the safety or efficacy of marketed products or product candidates in development; and (8) integration activities with acquired companies.
The forward-looking statements contained in this press release speak only as of the date of this press release, and Takeda undertakes no obligation to revise or update any forward-looking statements to reflect new information, future events or circumstances after the date of the forward-looking statement. If Takeda does update or correct one or more of these statements, investors and others should not conclude that Takeda will make additional updates or corrections.