AMAG Pharmaceuticals, Inc. AMAG today announced that new data from
two pivotal phase III clinical trials were presented at the American Society
of Hematology's (ASH) annual meeting in Atlanta, Georgia. The phase III trials
evaluated the use of ferumoxytol in 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 the United States.
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 U.S. Food and Drug
Administration (FDA) this month. In the United States, Feraheme is currently
indicated only for the treatment of iron 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 European Union (E.U.) regulators is the
mean change in 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. Saroj Vadhan-Raj, a principal investigator of the IDA-301
study and Professor and Chief of the Section of Cytokines & Supportive
Oncology at University of Texas MD Anderson Cancer Center. “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 Sunday, December 9, 2012 at the ASH
annual meeting.
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 Sunday, December 9, 2012 at
the ASH annual meeting.
One Gram Total Dose Infusion Study
Dr. Michael Auerbach, Clinical Professor at Georgetown University Medical
Center, presented new data at ASH from an exploratory study that 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.
These data are being presented in a poster session today at the ASH annual
meeting.
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