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Affymax and Takeda Announce Analyses from OMONTYS® (peginesatide) Injection Phase 3 Dialysis Studies Presented at 2012 American Society of Nephrology Meeting

November 1, 2012

Post-Hoc Data Provide Additional Information on Iron Utilization

PALO ALTO, Calif. and DEERFIELD, Ill. – November 1, 2012 (BUSINESS WIRE) – 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 Dialysis
Anemia 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.

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.



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.

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.

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.

Adverse reactions
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.

Please click here for Full Prescribing Information, including Boxed WARNINGS and Medication Guide, or visit www.omontys.com.

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 potential 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.tpna.com.

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.

SOURCE: Affymax, Inc. and Takeda Pharmaceuticals U.S.A., Inc.


Takeda Pharmaceuticals U.S.A., Inc.
Jocelyn M. Gerst, 224-554-5542
[email protected]