LEXINGTON, Mass., May 21, 2013 (GLOBE NEWSWIRE) -- AMAG Pharmaceuticals, Inc. (Nasdaq:AMAG) announced that a new sub-group analysis from IDA-301, a phase III, randomized, placebo-controlled clinical trial, will be presented today at a poster session of the Digestive Disease Week 2013 (DDW) meeting in Orlando, Florida. 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. The sub-group analysis being presented today at DDW is based on 231 patients in IDA-301 with gastrointestinal (GI) disease. Of these patients, 173 were randomized to the ferumoxytol treatment arm and 58 to the placebo arm.
IDA-301 was a multicenter trial designed to compare the safety and efficacy of a one gram course of ferumoxytol versus placebo in adult patients with IDA who had failed or could not tolerate oral iron treatment, regardless of the underlying cause. Ferumoxytol is an IV iron treatment currently approved in the United States for the treatment of IDA in adult chronic kidney disease patients. IDA-301 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 GI disease.
The primary efficacy endpoint of this study for the 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 GI sub-group analysis, 82.1% of ferumoxytol-treated patients achieved an increase of > 2.0 g/dL in hemoglobin compared to 1.7% of patients who received placebo at week 5, meeting the protocol defined measure of superiority (p<0.0001). The mean change in hemoglobin in ferumoxytol-treated GI patients from baseline to week 5 was 2.8 g/dL, compared to no increase (-0.1 g/dL) in GI 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 GI sub-group treated with ferumoxytol demonstrated an 11.6 point improvement in self-reported fatigue compared to a 7.9 point improvement in those who received placebo (p=0.0335).
"Patients with GI disease, including inflammatory bowel disease, often develop iron deficiency anemia, and most live with the symptoms associated with IDA, including extreme fatigue, " said Dr. Charles F. Barish, a gastroenterologist at Wake Gastroenterology in Raleigh, North Carolina and a Principal Investigator in the trial. "The data from this study showed a direct correlation between a rise in hemoglobin levels and improvements in patients' self-reported measures of fatigue. GI 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 GI disease who have previously had an unsatisfactory response to oral iron therapy."
In the GI sub-group, the rate of reported adverse events (AEs) was higher among ferumoxytol-treated patients (48.6%) than in patients that received placebo (44.8%). The overall rate of serious adverse events (SAEs) was comparable between the two treatment groups, with SAEs reported in 2.9% of ferumoxytol-treated patients, compared to 3.4% 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 GI disease. However, the incidence of reported AEs was consistent with that seen in the overall IDA population.
Poster Information
The poster, entitled "Evaluation of Ferumoxytol Treatment for Iron Deficiency Anemia in Patients with Gastrointestinal Disorders who have a History of Unsatisfactory Oral Iron Therapy: Results of a Phase III, Randomized, Placebo-Controlled Study," located at Hall WA1, will be presented on Tuesday, May 21, from 8:00 a.m. to 5:00 p.m., and poster authors will be available for a question-and-answer session from noon to 2:00 p.m.
About Iron Deficiency Anemia
More than 4 million Americans have iron deficiency anemia, many of whom are patients with gastrointestinal disease including bleeding in the upper and/or lower bowel, inflammatory bowel disease and malabsorption disorders.1 Other causes of IDA include chronic kidney disease, abnormal uterine bleeding, 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 GI patients in IDA-301 , 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, 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.
1Source: Cancer - US Census, Age-adjusted SEER incidence, primary market research, "Managing patients with Chemotherapy induced anemia": (2008), "Saving costs in cancer anemia management. Recognizing functional iron deficiency (FID) and rationalizing EPO therapy." (2002). GI - US Census, USRDS, DataMonitor Pipeline Insight: Inflammatory Bowel Disease, studies by Kappelman, and Tack, http://www.uchospitals.edu/pdf/uch_007937.pdf, http://www.ncbi.nlm.nih.gov/pubmed/15932566, http://www.haematologica.org/cgi/reprint/haematol.2009.009985v1.pdf. AUB and PP - AMAG primary market research, http://www.mdguidelines.com/dysfunctional-uterine-bleeding, National Vital Statistics Reports (NVSR), http://emedicine.medscape.com/article/257007-overview, "Have we forgotten the significance of postpartum iron deficiency?" (2005).