PALO ALTO, Calif. & DEERFIELD, Ill.--(BUSINESS WIRE)--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 24th 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.
In these studies, the most common adverse events (greater than ≥10%) were dyspnea, diarrhea, nausea, cough and arteriovenous fistula site complication.
"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 Dialysis
Anemia 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.
OMONTYS is contraindicated in patients with uncontrolled hypertension and in patients who have had serious allergic reactions to OMONTYS.
Warnings and Precautions
Increased 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.
Hypertension (see Contraindications): Appropriately control hypertension prior to initiation of and during treatment with OMONTYS. Reduce or withhold OMONTYS if blood pressure becomes difficult to control.
Serious allergic reactions (see Contraindications): Serious allergic reactions have been reported with OMONTYS. Immediately and permanently discontinue OMONTYS and administer appropriate therapy if a serious allergic reaction occurs.
Lack or loss of response to OMONTYS: Initiate a search for causative factors. If typical causes of lack or loss of hemoglobin response are excluded, evaluate for antibodies to peginesatide.
Dialysis management: Patients receiving OMONTYS may require adjustments to dialysis prescriptions and/or increased anticoagulation with heparin to prevent clotting of the extracorporeal circuit during hemodialysis.
Laboratory monitoring: Evaluate transferrin saturation and serum ferritin prior to and during OMONTYS treatment. Administer supplemental iron therapy when serum ferritin is less than 100mcg/L or when serum transferrin saturation is less than 20%. Monitor hemoglobin every 2 weeks until stable and the need for RBC transfusions is minimized. Then, monitor monthly.
Most common adverse reactions in clinical studies in patients with CKD on dialysis treated with OMONTYS were dyspnea, diarrhea, nausea, cough, and arteriovenous fistula site complication.
OMONTYS 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.
About Affymax, Inc.
Affymax, Inc. is a biopharmaceutical company based in Palo Alto, California. Affymax's mission is to discover, develop and deliver innovative therapies that improve the lives of patients with kidney disease and other serious and often life-threatening illnesses.
The company's first marketed product, OMONTYS, was approved by the U.S. Food and Drug Administration (FDA) in March 2012. For additional information on Affymax, please visit www.affymax.com.
Affymax Forward-Looking Statement
This release contains forward-looking statements, including statements regarding the importance of the EMERALD results, the potential advantages of OMONTYS, the continuation and success of Affymax's collaboration with Takeda and the commercialization of OMONTYS. Affymax's actual results may differ materially from those indicated in these forward-looking statements due to risks and uncertainties, including risks relating to the factors affecting the commercial potential of OMONTYS, the continued safety and efficacy of OMONTYS, industry and competitive environment, regulatory requirements by the FDA or other regulatory authorities, including post-marketing studies, trials and Risk Evaluation and Mitigation Strategy, the potential for disruptions to supply, financing requirements and our ability to access capital and other matters that are described in Affymax's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. Affymax undertakes no obligation to update any forward-looking statement in this press release.
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
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