Potential New Treatment Option for Iron Deficiency Anemia Patients with a History of Unsatisfactory Oral Iron Therapy- Results of a Phase III, Randomized, Open-Label, Active-Controlled Trial of Ferumoxytol.

While oral iron is the preferred first-line treatment for patients with iron deficiency anemia (IDA), there are patients who cannot take oral iron, do not tolerate it or do not adequately respond to oral iron. In the US and Canada, the only approved treatment options for these patients are the iron dextrans, which have boxed safety warnings and inconvenient dosing regimens. Therefore, many of these anemic patients do not receive IV iron, and remain inadequately treated and symptomatic. In the EU, several IV irons, including iron sucrose (IS), are approved for second line use. Few studies have evaluated the IV irons in head-to-head studies. Ferumoxytol (FER) is a new IV iron approved for the treatment of IDA in patients with chronic kidney disease (CKD) that is formulated to allow for bolus IV injection. This randomized, controlled trial was designed to investigate the efficacy and safety of FER compared to IS for the treatment of IDA in patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used.

The study was designed to demonstrate non-inferiority and consisted of a 14 day screening period, treatment and a 5 week follow-up period. Key inclusion criteria included a Baseline hemoglobin (Hgb) less than 10 g/dL and >7 g/dL, and transferrin saturation (TSAT) < 20%. Patients were randomized 2:1 to receive either FER, administered as 2 injections of 510 mg 5±3 days apart, or IS, administered as 5 infusions or injections of 200 mg on 5 non-consecutive days over a 14 day period.

A total of 605 subjects were randomized to the 2 treatment arms (FER, n= 406; IS, n=199). FER demonstrated non-inferiority to IS in the proportion of subjects with a >2.0 g/dL increase in Hgb at any time from Baseline to Week 5 (the primary efficacy endpoint), compared to those treated with IS, (FER, 84%; IS 81%) with the lower bound of the 95% CI [-3.89%] above the predefined non inferiority margin [-15%]. In addition at each post-treatment time point, a higher percentage of FER-treated subjects achieved a >2.0 g/dL increase in Hgb compared to those treated with IS. FER also achieved non-inferiority to IS in the mean change in Hgb from Baseline to Week 5 with a robust 2.7g/dL increase in Hgb compared to 2.4g/dL with IS (the lower bound of the 95% CI [0.06g/dL] was above the predefined non-inferiority margin [-0.5g/dL]); this treatment difference (0.3 g/dL) was statistically significant (p=0.0124), and FER actually achieved superiority over IS.

The overall rates of adverse events (AEs) and related AEs were lower in the FER group compared to IS-treated subjects. The serious adverse event (SAE) rate was higher in FER-treated subjects (FER, 4.2%; IS, 2.5%), but no pattern or safety trend was observed to suggest a specific safety signal; treatment-related SAEs were reported in 2 (0.5%) FER-treated subjects (1 anaphylactoid reaction and 1 hypertension). Protocol-defined AEs of Special Interest (signs/symptoms of hypotension or hypersensitivity associated with IV iron use) were reported at a higher rate in IS-treated subjects compared to the FER treatment group (IS, 5.0%; FER, 2.7%). Cardiovascular AE rates were comparable in the 2 treatment groups (1.0%). Overall, the safety profile of FER was comparable to that of IS and no new safety signals were identified.

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Proportion of Subjects with > 2 g/dL Increase in Hgb at Any Time from Baseline to Week 5 (ITT)

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Proportion of Subjects with > 2 g/dL Increase in Hgb at Any Time from Baseline to Week 5 (ITT)

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In this randomized, controlled trial, the efficacy and safety of 2 doses of FER were shown to be comparable to IS in treating IDA patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. For this IDA patient population, which has limited treatment options in the US and Canada, FER may offer an important, new treatment option with a convenient 2 dose regimen.

Off Label Use: Feraheme (ferumoxytol) injection. For treatment of iron deficiency anemia in non-CKD patients. Bernard:AMAG Pharmaceuticals, Inc.: Employment. Strauss:AMAG Pharmaceuticals, Inc.: Employment. Cressman:AMAG Pharmaceuticals, Inc.: Employment. Li:AMAG Pharmaceuticals, Inc.: Employment. Allen:AMAG Pharmaceuticals, Inc.: Employment.