LEXINGTON, Mass., May 6, 2013 (GLOBE NEWSWIRE) -- AMAG Pharmaceuticals, Inc. (Nasdaq:AMAG) today announced that a new sub-group analysis from IDA-301, a phase III, randomized, placebo-controlled clinical trial, will be presented today at the first poster session of the American College of Obstetrics and Gynecology (ACOG) annual meeting in New Orleans, Louisiana. In the full IDA-301 study, 608 adult patients with iron deficiency anemia (IDA) who had failed or could not tolerate oral iron were treated with ferumoxytol and 200 received placebo, with the demographics and all baseline parameters well balanced between the two treatment groups. The sub-group analysis being presented today at ACOG is based on 344 patients in IDA-301 with abnormal uterine bleeding (AUB), the most frequent underlying cause for IDA in this study, with 260 AUB patients randomized to ferumoxytol and 84 to placebo.
IDA-301 was a randomized, double-blind, placebo-controlled multicenter trial designed to compare the safety and efficacy of a one gram course of ferumoxytol, an IV iron treatment currently approved in the United States for the treatment of IDA in adult chronic kidney disease patients, versus placebo in adult patients with IDA who had failed or could not tolerate oral iron treatment, regardless of the underlying cause. This was one of two studies that formed the foundation for AMAG's supplemental new drug application (sNDA) in the United States, which was filed in December 2012. AMAG's sNDA seeks to expand the use of Feraheme® (ferumoxytol) for adult IDA patients who have failed or could not tolerate oral iron, including those patients with AUB.
The primary efficacy endpoint of this study for U.S. Food and Drug Administration (FDA) 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 (EU) regulators is the mean change in hemoglobin from baseline to week 5. In the AUB subgroup analysis, 87.3% of ferumoxytol-treated patients achieved an increase of > 2.0 g/dL in hemoglobin compared to 3.6% of patients who received placebo, meeting the protocol defined measure of superiority (p<0.0001). The mean change in hemoglobin in ferumoxytol-treated AUB patients was 2.8 g/dL, compared to no increase (0.0 g/dL) in AUB patients receiving placebo (p<0.0001). These results paralleled those in the total study population.
As a pre-defined secondary endpoint in the IDA-301 study, patients were asked to report on measures of fatigue using the Functional Assessment of Chronic Illness Therapy (FACIT) instrument. Patients in the AUB subgroup treated with ferumoxytol demonstrated a 14.0 point improvement in self-reported fatigue compared to a 7.7 point improvement in those who received placebo (p<0.001).
"Many women with AUB suffer from the symptoms of iron deficiency anemia, such as serious fatigue, which can have a negative impact on their quality of life," said Dr. Melvin H. Seid, Director of Clinical Research at Lyndhurst Gynecologic Associates in Winston Salem, N.C. and a Principal Investigator for the trial. "Participants in this trial who were treated with ferumoxytol had significant increases in hemoglobin, which directly correlated to improvements in self-reported measures of fatigue. AUB patients with iron deficiency anemia who have not responded well to oral iron supplementation have a need for additional treatment options. The analysis from this study supports the potential of ferumoxytol as a new treatment option for patients with IDA from AUB who have previously had an unsatisfactory response to oral iron therapy."
In the AUB sub-group, the rate of reported adverse events (AEs) was higher among ferumoxytol-treated patients (47.7%) than in patients that received placebo (46.4%), although no new safety signals, outside those described in the current FDA-approved label for ferumoxytol, were observed in this study. The overall rate of serious adverse events (SAEs) was comparable between the two treatment groups, with SAEs reported in 1.5% of ferumoxytol-treated patients, compared to 3.6% of patients that received placebo. Related AEs and AEs of special interest were higher in ferumoxytol-treated patients in both the overall population and in patients with AUB. The frequency of reported events was consistent with the established safety profile of ferumoxytol, as described in the full prescribing information (see package insert).
Poster Information
Poster No. 85, titled "Evaluation of Ferumoxytol for Treating Iron Deficiency Anemia from Abnormal Uterine Bleeding" will be presented on Monday, May 6, from 10:30 a.m. to 5:00 p.m., and poster authors will be available for a question-and-answer session from 3:00 p.m. to 4:00 p.m.
About Iron Deficiency Anemia
More than 4 million Americans have iron deficiency anemia, of whom approximately one million are women with dysfunctional or abnormal uterine bleeding who are treated with a variety of surgical and/or medical management techniques.1 The remaining 3 million Americans suffer from anemia due to other causes; the underlying diseases or conditions causing IDA in these patients include chronic kidney disease, gastrointestinal disorders, inflammatory diseases and chemotherapy-induced anemia. Many IDA patients fail treatment with oral iron due to intolerability, lack of absorption or side effects.
About AMAG
AMAG Pharmaceuticals, Inc. is a specialty pharmaceutical company that manufactures and markets Feraheme® in the United States. Along with driving organic growth of its lead product, AMAG intends to expand its portfolio with additional commercial-stage specialty pharmaceuticals. The company is seeking complementary products that leverage the company's commercial footprint and focus on hematology and oncology centers and hospital infusion centers. For additional company information, please visit www.amagpharma.com.
About Feraheme® (ferumoxytol)/Rienso
In the United States, Feraheme (ferumoxytol) Injection for Intravenous (IV) use is indicated for the treatment of iron deficiency anemia in adult chronic kidney disease (CKD) patients. Feraheme received marketing approval from the U.S. Food and Drug Administration on June 30, 2009 and was commercially launched by AMAG in the U.S. shortly thereafter.
Ferumoxytol is protected in the U.S. by three issued patents covering the composition and dosage form of the product. Each issued patent is listed in the FDA's Orange Book. These patents are set to expire in 2020; a request for patent term extension has been filed, which, if granted, may extend the patent term to 2023 for one of the patents.
Ferumoxytol received marketing approval in Canada in December 2011, where it is marketed by Takeda as Feraheme, and in the European Union in June 2012 and Switzerland in August 2012, where it is marketed by Takeda as Rienso®.
Feraheme is contraindicated in patients with known hypersensitivity to Feraheme or any of its components.
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 conducted as part of the CKD development program, 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 in3.7% (63/1,726) of subjects.
Severe adverse reactions of clinically significant hypotension have been reported in the post-marketing experience of Feraheme. In clinical studies conducted as part of the CKD development program, 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.
In clinical trials of patients with IDA and CKD, the most commonly occurring adverse reactions in Feraheme treated patients versus oral iron treated patients (reported in ≥ 2% of 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 these 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.
For additional U.S. product information, including 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 sub-group analysis on patients in IDA-301 with AUB, the expectations and expected timing for regulatory review of the submission and outcome of the supplemental new drug application for the broader IDA indication and the availability of treatment options for patients, and the company's interactions with the FDA, the patent term extension 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 of the US, (6) the risk of an Abbreviated New Drug Application (ANDA) filing following the FDA's recently published draft bioequivalence recommendation for ferumoxytol, and (7) other risks identified in our Securities and Exchange Commission filings, including our Quarterly Report on Form 10-Q for the three months ended March 31, 2013 and subsequent filings with the SEC. We caution you not to place undue reliance on any 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.
AMAG Pharmaceuticals and Feraheme are registered trademarks of AMAG Pharmaceuticals, Inc.
Rienso is a registered trademark of Takeda Pharmaceutical Company Limited.
(1) Jahn MR, Andreasen HB, Fütterer S, et al. A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer®), a new intravenous iron preparation and its clinical implications. Eur J Pharm Biopharm 2011;78:480-491.