Patients with chronic anemia (i.e., anemia of inflammation) frequently find that iron repletion cannot be achieved with oral iron fortificants. The current standard of care for these patients is infusion of intravenous (IV) iron-carbohydrate complexes. These complexes must be processed in the liver to render iron available for erythropoiesis. Therefore, after administration of an iron-carbohydrate complex, serum is temporarily iron-overloaded with catalytically active iron capable of initiating lipid peroxidation endothelial dysfunction, and added debilitating effects of oxidative stress. As a result, patients may experience serious side effects, both acutely and chronically. Preliminary studies of sodium ferricitropyrophosphate (FCP), a low molecular weight iron chelate, indicate that FCP, administered IV, may be useful to treat chronic anemia that is refractory to oral iron. The SBIR Phase I research proposed herein is designed to support the efficacy and safety of aqueous FCP solutions as a new IV iron treatment for this indication. The proposed studies will advance development of this potential product in two significant ways: " Specific Aim 1 (Safety): Determine whether FCP is stable in serum for 48 hours. Evaluation of the stability and redox activity of FCP in serum over a 48-hour period will show what potential FCP has to cause oxidative stress. "Specific Aim 2 (Safety): Formulate FCP to optimize biocompatibility for IV administration. In order to minimize side effects of administration, FCP should be formulated in aqueous solution, pH 7.4, isotonic with serum. If the resulting data demonstrate reduced potential for oxidative stress and enhancement of biocompatibility after IV administration, the data will lend credence to three expected benefits of FCP- containing IV products: (1) FCP solutions, administered using current clinical protocols, will exhibit enhanced efficacy and safety for the patient. (2) Rapid and complete apotransferrin saturation after infusion of FCP solutions may enable more efficient hemoglobin repletion using lower doses of iron. (3) Successful clinical implementation of FCP solutions may encourage development of self- administration devices, enabling daily infusion of very low doses of iron as FCP by the patient. Expected sweeping changes to the economics of health care are predicted to benefit companies which develop products having competitive advantages such as safety, convenience, and lower costs. If IV FCP therapy is successful, it could be a positive agent for change, one which enables small business growth and supports the mission of the Agency. Currently, the IV iron drug market is estimated at $560 million in the United States and $1 billion globally.
Patients with chronic anemia cannot use oral iron supplements to increase their hemoglobin levels and must undergo intravenous therapy with iron-carbohydrate complexes. Frequently they experience both acute and chronic side effects after treatment. The proposed research supports development of a new intravenous iron therapy which promises to provide effective hemoglobin repletion with enhanced efficacy and safety.