Affymax and Takeda Announce Analyses from OMONTYS® (peginesatide) Injection Phase 3 Dialysis Studies Presented at 2012 American Society of Nephrology Meeting
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
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
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.
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
OMONTYS is contraindicated in patients with uncontrolled hypertension.
Warnings and Precautions
Increased mortality, myocardial infarction, stroke, and
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
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
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
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,
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
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statements include statements regarding Takeda's plans, outlook,
strategies, results for the future, and other statements that are not
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"assume," "continue," "seek," "pro forma," "potential," "target,"
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expressions of the negative thereof. Forward-looking statements are
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cause actual results or experience to differ materially from that
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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)
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or efficacy of marketed products or product candidates in development;
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The forward-looking statements contained in this press release speak
only as of the date of this press release, and Takeda undertakes no
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Takeda will make additional updates or corrections.