The Evaluation of Long-Term Ferumoxytol Use as An Iron Replacement Therapy In Patients with Iron Deficiency Anemia

Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. The World Health Organization (WHO) estimates that as many as 1.6 billion people worldwide (25% of the world’s population) have IDA, and the National Center for Health Statistics estimates that 3.4 million people in the US have IDA. Various underlying conditions have been linked to IDA, which in industrialized nations primarily include chronic kidney disease (CKD), menstrual and postpartum blood loss, pregnancy, gastrointestinal (GI) blood loss, and cancer. Regardless of underlying cause, iron replacement therapy is essential for increasing iron stores and raising hemoglobin levels in patients with IDA. Typically, one gram of iron is the standard IV iron therapeutic dose for the management of IDA. Ferumoxytol is approved in the US for the treatment of IDA in adult subjects with CKD and is marketed under the trade name Feraheme® (ferumoxytol) Injection. Ferumoxytol is administered as two IV injections of 510 mg (17 mL) 3 to 8 days apart, for a total cumulative dose of 1.02 g.

To provide a convenient, safe, and effective method for increasing iron in patients with IDA and a history of unsatisfactory oral iron therapy, AMAG is undertaking a global Phase III clinical development program. This program includes a randomized, double-blind, placebo-controlled trial in 800 subjects (ClinicalTrials.gov NCT01114139) followed by a sixth-month, open-label extension trial (ClinicalTrials.gov NCT01114217). The primary objective of the double-blind placebo-controlled study is to evaluate the efficacy and safety of a 1.02 g course of IV ferumoxytol, administered as two doses of 510 mg each, compared with placebo (normal saline). This trial will randomize subjects to ferumoxytol or placebo at a ratio of 3:1. Subjects will have a variety of underlying conditions including ongoing abnormal uterine bleeding (AUB), GI disorders (eg, inflammatory bowel disease, gastric bypass), cancer, postpartum blood loss, and other conditions such as nutritional iron deficiency, heart failure, and rheumatoid arthritis. Following study completion (a 5-week treatment period) all subjects will have an opportunity to enroll into the extension trial (NCT01114217), which will evaluate the safety and efficacy of ferumoxytol for the episodic treatment of IDA over a 6-month period. In both trials, key efficacy endpoints will be based on evaluations of hemoglobin through 5 weeks following treatment with ferumoxytol. Additional assessments will include change in transferrin saturation, and the impact of ferumoxytol treatment on both the use of erythropoiesis stimulating agents and the need for blood transfusions. Both of these trials will also include patient reported outcomes to assess the impact of IV iron therapy on anemia symptoms and health-related quality of life (fatigue, energy). Additionally, detailed information on healthcare utilization will be collected.

In addition to providing efficacy, safety, and patient reported outcome information on the administration of ferumoxytol for the treatment of IDA in a broad patient population, these trials (NCT01114139 and NCT01114217) will contribute novel data regarding the requirement for repeat therapy with IV iron and the safety and efficacy of long-term repeat use of IV iron in the treatment of IDA.

Poma:AMAG Pharmaceuticals, Inc.: Employment. Diana:AMAG Pharmaceuticals, Inc.: Employment. McLaughlin:AMAG Pharmaceuticals, Inc.: Employment. Kausz:AMAG Pharmaceuticals, Inc.: Employment.