AMAG Pharmaceuticals, Inc. has submitted a supplemental new drug application (sNDA) to the United States Food and Drug Administration (FDA) for Feraheme (ferumoxytol) injection for Intravenous (IV) use. The sNDA requests FDA approval to expand the indication for ferumoxytol beyond the current indication for the treatment of iron deficiency anaemia (IDA) in adult patients with chronic kidney disease (CKD) to all adult patients with IDA who have failed or could not tolerate oral iron treatment. The application includes data from two well-controlled phase III clinical trials of more than 1,400 patients.

“This submission marks an important corporate milestone and represents the culmination of several years of work here at AMAG. The regulatory approval of Feraheme for a broader IDA patient population would expand our market opportunity in the existing US IV iron market, beyond our current CKD indication,” said William Heiden, president and chief executive officer of AMAG. “We believe that Feraheme, if approved for this indication, could provide a new treatment option for patients suffering from iron deficiency anemia who cannot tolerate or do not respond to oral iron therapy.”

The sNDA submission is based on data from a global phase III programme that evaluated the use of ferumoxytol in a broad range of adult IDA patients, all of whom had failed or could not tolerate oral iron treatment. More than 1,400 patients were enrolled in the two phase III clinical trials, IDA-301 (placebo comparator) and IDA-302 (active comparator). Both studies achieved their primary efficacy endpoints, with meaningful improvements in haemoglobin from baseline to the 35-day endpoint of the studies. Adverse events and serious adverse events associated with IV iron therapy, including hypersensitivity reactions, were reported in both studies. No new safety signals, outside of those described in the current Feraheme (ferumoxytol) label, were observed with ferumoxytol treatment in these studies. These clinical trials also included patient-reported outcomes data as pre-specified secondary and exploratory endpoints. These outcomes endpoints, including quantitative measures of patients’ fatigue and measures of quality of life, captured the negative pre-treatment impact anaemia has on these patients’ lives – and the significant improvement in these scores following a one gram course of therapy with ferumoxytol.

Patients with anaemia due to other causes, the underlying diseases or issues causing IDA include abnormal uterine bleeding, gastrointestinal disorders, inflammatory diseases and chemotherapy-induced anaemia. Many IDA patients fail treatment with oral iron due to intolerability or side effects.

AMAG Pharmaceuticals, Inc. is a specialty pharmaceutical company that manufactures and markets Feraheme in the United States. The company is seeking complementary products that leverage the company’s commercial footprint and focus on haematology and oncology centres and hospital infusion centres.

In the United States, Feraheme (ferumoxytol) injection for IV use is indicated for the treatment of iron deficiency anaemia in adult CKD patients. Feraheme received marketing approval from the FDA on June 30, 2009 and was commercially launched by AMAG in the US shortly thereafter. 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 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.

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 per cent (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 per cent (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 per cent (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 three months following the last Feraheme dose. Feraheme will not affect X-ray, CT, PET, SPECT, ultrasound, or nuclear imaging.

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 diarrhoea (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 two or more Feraheme treated patients included hypotension, infusion site swelling, increased serum ferritin level, chest pain, diarrhoea, dizziness, ecchymosis, pruritus, chronic renal failure, and urticaria.

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.