AMAG Pharmaceuticals, Inc. (NASDAQ: 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. 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.
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. 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.
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.