New Data from an Additional Study Exploring 1 Gram Total Dose
Infusion of Ferumoxytol also Presented
from two pivotal phase III clinical trials were presented at the
Georgia
subjects with iron deficiency anemia (IDA), regardless of the underlying
cause of the anemia, who had failed or could not tolerate oral iron
treatment. New data from an investigator-initiated study evaluating a
one gram 15-minute infusion of ferumoxytol are also being presented at
ASH; the current approved dosing of ferumoxytol is two 510 mg
injections, three to eight days apart.
Two poster sessions highlighted the safety and efficacy data from each
of the phase III clinical trials: IDA-301 and IDA-302. In addition, an
oral presentation contained patient-reported outcome data from IDA-301,
which demonstrated a direct correlation between the rise in hemoglobin
and improvement in patient-reported measures of fatigue. Data from these
two clinical trials will be the foundation for AMAG’s supplemental new
drug application (sNDA) in
More than 4 million Americans have iron deficiency anemia; 1.6 million
of whom are estimated to have chronic kidney disease (CKD), while the
other 2.4 million suffer from anemia due to other causes.1
For these patients with anemia due to other causes, the underlying
diseases or conditions causing IDA include abnormal uterine bleeding,
gastrointestinal disorders, inflammatory diseases and
chemotherapy-induced anemia. Many IDA patients fail treatment with oral
iron due to intolerability or side effects.2
AMAG’s sNDA will seek to expand the use of Feraheme® (ferumoxytol) for
all adult iron deficiency anemia patients with a history of
unsatisfactory use of oral iron. The company expects to submit the sNDA
to the
States
deficiency anemia in adult CKD patients.
IDA-301 Study and Results
IDA-301 was a double-blind, placebo-controlled trial designed to compare
the safety and efficacy of a one gram intravenous (IV) course of
ferumoxytol to IV saline given as placebo. In this study, 608 subjects
were treated with ferumoxytol and 200 received placebo, with the
demographics and all baseline parameters well balanced between the two
treatment groups. The primary efficacy endpoint for U.S. regulators is
the proportion of subjects who achieved a ≥ 2.0 g/dL increase in
hemoglobin at any time from baseline to week 5; the primary efficacy
endpoint for
hemoglobin from baseline to week 5.
In the IDA-301 trial, ferumoxytol achieved both primary efficacy
endpoints. Over 80% of study participants treated with ferumoxytol
achieved an increase of ≥ 2.0 g/dL in hemoglobin compared to only 5.5%
of subjects who received placebo, meeting the protocol defined measure
of superiority (p<0.0001). The mean change in hemoglobin in
ferumoxytol-treated subjects was 2.7 g/dL, compared to a mean 0.1 g/dL
increase in subjects receiving placebo (p<0.0001).
Data from IDA-301 also showed a direct correlation between a rise in
hemoglobin and improvement in subject-reported fatigue scores using the
Functional Assessment of Chronic Illness Therapy (FACIT) instrument. At
baseline, IDA-301 participants reported mean FACIT-Fatigue levels of 24,
which are comparable to those described in the medical literature for
anemic cancer patients receiving chemotherapy.3 Following a
one gram course of therapy with ferumoxytol, the subjects in this study
reported a significant improvement in fatigue scores (less fatigue) with
a mean 12 point increase in FACIT-Fatigue scores from baseline to week 5
(p<0.05). In published literature, the U.S. mean FACIT-Fatigue score in
a randomly selected group of 1,075 subjects was 40.4 In
IDA-301, subjects treated with ferumoxytol achieved mean FACIT-Fatigue
scores of 36 at week 5, close to those of the general U.S. population.
“Symptoms of anemia can have a negative impact on a patient’s quality of
life,” said Dr.
IDA-301 study and Professor and Chief of the Section of Cytokines &
Supportive Oncology at
“Subjects in IDA-301 treated with ferumoxytol had significant increases
in hemoglobin levels and we observed a direct correlation between a rise
in hemoglobin and an improvement in these subjects’ measures of fatigue.
Patients with iron deficiency anemia and an unsatisfactory history with
oral iron have a real need for additional treatment options and the data
from the studies presented at ASH suggest that ferumoxytol may have the
potential to address that need.”
In IDA-301, the overall rate of reported adverse events was higher in
the ferumoxytol group than in the placebo group, although no new safety
signals, outside of those described in the current Feraheme®
(ferumoxytol) label, were observed in this study. The overall rate of
serious adverse events (SAEs) was comparable between the two treatment
groups, and two related SAEs of hypersensitivity, including one
anaphylactic reaction, were reported in ferumoxytol-treated patients.
The patient-reported outcomes data are being presented in an oral
presentation today at the ASH annual meeting. The safety and efficacy
data from IDA-301 were presented in a poster session on
9, 2012
IDA-302 Study and Results
IDA-302 was a multicenter, open-label, active-controlled, international
clinical trial designed to compare treatment between ferumoxytol and
iron sucrose. Subjects were randomized 2:1 to receive a one gram IV
course of either ferumoxytol (n=406) or iron sucrose (n=199), and the
demographics and all baseline parameters were well balanced between the
two treatment groups. The primary efficacy endpoint for U.S. regulators
is the proportion of subjects who achieved a ≥ 2.0 g/dL increase in
hemoglobin at any time from baseline to week 5; the primary efficacy
endpoint for E.U. regulators is the mean change in hemoglobin from
baseline to week 5.
In the IDA-302 trial, ferumoxytol achieved both primary efficacy
endpoints. Subjects treated with ferumoxytol achieved a significantly
greater mean increase in hemoglobin of 2.7 g/dL at week 5, compared to a
2.4 g/dL increase for those treated with iron sucrose (p<0.013). By week
5, 84% of ferumoxytol-treated subjects achieved a ≥ 2.0 g/dL increase in
hemoglobin, compared to 81% of those treated with iron sucrose.
The overall rates of adverse events and related adverse events were
comparable in ferumoxytol- and iron sucrose-treated subjects, and
included many attributable to comorbid disease. However, the overall
rate of SAEs, both related and unrelated as assessed by the
investigator, was higher in ferumoxytol-treated subjects. The SAEs in
two ferumoxytol-treated subjects were reported as related to the study
drug by the investigators; these included one anaphylactoid reaction and
one case of hypertension. In this study, no new safety signals, outside
of those described in the current Feraheme® (ferumoxytol) label, were
identified.
These data were presented in a poster session on
2012
One Gram Total Dose Infusion Study
Dr.
Medical Center
evaluated the safety and efficacy of the administration of a full one
gram dose of ferumoxytol as a single 15-minute infusion (the approved
ferumoxytol dosing regimen is two 510 mg injections three to eight days
apart). In this investigator-initiated, AMAG-supported study, which was
conducted under an investigator-held investigational new drug
application (IND), sixty adult subjects with IDA associated with a
variety of underlying causes were studied and all received ferumoxytol.
After a one-gram infusion of ferumoxytol, an increase of ≥ 2.0 g/dL in
hemoglobin was reported in 58% of subjects by week 4 and 86% of subjects
by week 8. The mean increase in hemoglobin from baseline was 2.1 g/dL at
week 4 and 2.6 g/dL at week 8. Thirteen subjects reported mild,
transient, transfusion-associated adverse events, one of which required
treatment. Fourteen patients reported mild, self-limited arthralgias,
myalgias and/or headache within 24-48 hours after treatment. No serious
adverse events were reported in this study.
Dr. Auerbach commented, “Many patients with IDA do not benefit from oral
iron therapy and suffer daily from anemia-related side effects. In this
study, a full one gram course of ferumoxytol therapy was administered in
a 15-minute infusion with no unexpected adverse events. Additionally,
clinically meaningful improvements in hemoglobin levels were achieved in
a majority of study participants after one 15-minute dose.”
These data are being presented in a poster session today at the ASH
annual meeting.
About AMAG
manufactures and markets Feraheme® (ferumoxytol) Injection for
Intravenous (IV) use in
information, please visit www.amagpharma.com.
About Feraheme® (ferumoxytol)/Rienso
In
(IV) use is indicated for the treatment of iron deficiency anemia in
adult chronic kidney disease (CKD) patients. Feraheme received marketing
approval from the
was commercially launched by AMAG in the US shortly thereafter.
Ferumoxytol received marketing approval in
where it is marketed by Takeda as Feraheme®, and in the
in
Takeda as Rienso®. For additional product information, please visit www.feraheme.com.
The important safety information below is based on
prescribing information.
Important Safety Information About Feraheme
Indication and contraindications
Feraheme ® (ferumoxytol) Injection for Intravenous (IV) is indicated for
the treatment of iron deficiency anemia in adult patients with chronic
kidney disease. Feraheme is contraindicated in patients with known
hypersensitivity to Feraheme or any of its components.
Warnings and precautions
Serious hypersensitivity reactions, including anaphylactic-type
reactions, some of which have been life-threatening and fatal, have been
reported in patients receiving Feraheme. Observe patients for
signs and symptoms of hypersensitivity during and after Feraheme
administration for at least 30 minutes and until clinically stable
following completion of each administration. Only administer the
drug when personnel and therapies are immediately available for the
treatment of anaphylaxis and other hypersensitivity reactions.
Anaphylactic type reactions, presenting with cardiac/cardiorespiratory
arrest, clinically significant hypotension, syncope, and
unresponsiveness have been reported in the post-marketing experience.
In clinical studies, serious hypersensitivity reactions were reported in
0.2% (3/1,726) of subjects receiving Feraheme. Other adverse reactions
potentially associated with hypersensitivity (e.g., pruritus, rash,
urticaria or wheezing) were reported in 3.7% (63/1,726) of subjects.
Severe adverse reactions of clinically significant hypotension have
been reported in the post-marketing experience. In clinical studies,
hypotension was reported in 1.9% (33/1,726) of subjects, including three
patients with serious hypotensive reactions. Monitor for signs and
symptoms of hypotension following each Feraheme injection. Excessive
therapy with parenteral iron can lead to excess storage of iron with the
possibility of iatrogenic hemosiderosis. Patients should be regularly
monitored for hematologic response during parenteral iron therapy,
noting that lab assays may overestimate serum iron and transferrin bound
iron values in the 24 hours following administration of Feraheme. As a
superparamagnetic iron oxide, Feraheme may transiently affect magnetic
resonance diagnostic imaging studies for up to 3 months following the
last Feraheme dose. Feraheme will not affect X-ray, CT, PET, SPECT,
ultrasound, or nuclear imaging.
Adverse reactions
In clinical trials, the most commonly occurring adverse reactions in
Feraheme treated patients versus oral iron treated patients reported in
≥ 2% of chronic kidney disease patients were diarrhea (4.0% vs. 8.2%),
nausea (3.1% vs. 7.5%), dizziness (2.6% vs. 1.8%), hypotension (2.5% vs.
0.4%), constipation (2.1% vs. 5.7%) and peripheral edema (2.0% vs.
3.2%). In clinical trials, adverse reactions leading to treatment
discontinuation and occurring in 2 or more Feraheme treated patients
included hypotension, infusion site swelling, increased serum ferritin
level, chest pain, diarrhea, dizziness, ecchymosis, pruritus, chronic
renal failure, and urticaria.
Post-marketing safety experience
The following adverse reactions have been identified during
post-approval use of Feraheme. Because these reactions are reported
voluntarily from a population of uncertain size, it is not always
possible to reliably estimate their frequency or establish a causal
relationship to drug exposure.
The following serious adverse reactions have been reported from the
post-marketing spontaneous reports with Feraheme: life-threatening
anaphylactic-type reactions, cardiac/cardiorespiratory arrest,
clinically significant hypotension, syncope, unresponsiveness, loss of
consciousness, tachycardia/rhythm abnormalities, angioedema, ischemic
myocardial events, congestive heart failure, pulse absent, and cyanosis.
These adverse reactions have occurred up to 30 minutes after the
administration of Feraheme injection. Reactions have occurred following
the first dose or subsequent doses of Feraheme.
For full prescribing information, please visit www.feraheme.com.
Forward-looking Statements
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995 and
other federal securities laws. Any statements contained herein which do
not describe historical facts, including but not limited to statements
regarding: the expected timing of submission and outcome of the
supplemental new drug application for the broader IDA indication are
forward-looking statements which involve risks and uncertainties that
could cause actual results to differ materially from those discussed in
such forward-looking statements.
Such risks and uncertainties include: (1) uncertainties regarding our
and Takeda’s ability to successfully compete in the intravenous iron
replacement market both in the US and outside the US, including the EU,
(2) uncertainties regarding our ability to successfully and timely
complete our clinical development programs and obtain regulatory
approval for Feraheme/Rienso in the broader IDA indication
both in the US and outside of the US, including the EU, (3) the
possibility that significant safety or drug interaction problems could
arise with respect to Feraheme/Rienso, (4) uncertainties
regarding the manufacture of Feraheme/Rienso, (5) uncertainties
relating to our patents and proprietary rights both in the US and
outside the US, and (6) other risks identified in our Securities and
Exchange Commission (SEC) filings, including our Quarterly Report on
Form 10-Q for the quarter ended September 30, 2012 and subsequent
filings with the
forward-looking statements, which speak only as of the date they are
made.
We disclaim any obligation to publicly update or revise any such
statements to reflect any change in expectations or in events,
conditions or circumstances on which any such statements may be based,
or that may affect the likelihood that actual results will differ from
those set forth in the forward-looking statements.
Pharmaceuticals, Inc.
Rienso is a registered trademark of
Limited
1 U.S. Census; U.S. Renal Data System, USRDS 2010 Annual
Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease
in
Institute of Diabetes and Digestive
2010: 41-42; Fishbane, S. et al. Iron Indices in CKD in the NHANES
1998-2004. Clin J Am Soc Nephrol. 2009 January; 4(1): 57–61.
2
Barton, James et al. Intravenous iron dextran therapy in patients
with iron deficiency and normal renal function who failed to respond to
or did not tolerate oral iron supplementation. Am J Medicine. 2000;
109: 27-32.
3 Cella D et al. Fatigue in Cancer
Patients Compared with Fatigue in the General United States Population.
Cancer 2002;94:2
4 Webster K et al. The functional
assessment of chronic illness therapy (FACIT) measurement system:
properties, applications, and interpretation. Health
Source:
AMAG Pharmaceuticals, Inc.
Amy Sullivan, 617-498-3303
