A recent review discussed the mode of action, pharmacokinetics and impact on patients’ lives with sucroferric oxyhydroxide, an iron-based phosphate binder, for the treatment of chronic kidney disease-mineral bone disorder. The paper, “Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide,” was published in the International Journal of Nephrology and Renovascular Disease.

Patients with renal function impairment frequently develop a syndrome called CKD-mineral bone disorder (CKD-MBD), characterized by abnormalities in bone and mineral metabolism, which leads to a variety of consequences such as low vitamin D, excess of phosphorus (hyperphosphatemia), altered bone density and morphology and increased risk of fracture. The treatment for CKD-MBD usually includes a recommendation to reduce the daily intake of phosphorus and pharmaceutical therapy by a series of now available medicines. Such drugs include vitamin D sterols, active vitamin D analogs, calcimimetics and phosphate binders.

Phosphate binders work by binding the phosphorus consumed through diet in the gastrointestinal track, preventing its absorption and raised levels in circulation. Phosphate binders can be either calcium-containing compounds or calcium-free compounds, depending on the calcium content in their composition. While calcium-containing compounds are efficient to lower phosphorus levels but are associated with a risk of hypercalcemia, calcium-free binders are an equal or slightly less effective alternative but are not associated with higher calcium levels, therefore reducing the risk for vascular calcifications. However, calcium-free binders, such as Sevelamer carbonate and Lanthanum carbonate, are associated with clinically significant side effects.

Adding to the lack of placebo-controlled clinical trials evaluating the impact of these medicines, there is still no consensus as to what the ideal phosphate-binder for the treatment of hyperphosphatemia is, leaving treatment mostly driven by clinical experience and individual evaluation of the patient.

Iron-based compounds are a new category of phosphate-binders, which include under-investigation compounds and also already available drugs, such as calcium-free iron-based phosphate binder sucroferric oxyhydroxide (Velphoro, PA21), a chewable tablet whose pharmacologically active part is Iron(III)-oxyhydroxide.

Iron-based compounds are not recommended for people suffering from hepatic, gastric diseases or with a history of hemochromatosis or other disorders characterized by iron accumulation, as these compounds might be accompanied by an iron increase.

Sucroferric oxyhydroxide was approved by the by the U.S. Food and Drug Administration (FDA) in November 2013 and by the European Medicines Agency (EMA) in August 2014 for the treatment of hyperphosphatemia in CKD patients receiving dialysis. Its mechanism of action is dependent on the presence of iron and its ability to bind phosphorus to the GI lumen occurs due to two mechanisms, one in the stomach and the other in the intestinal lumen, both leading to the excretion of bound phosphorus in the feces. The most important concerns include taking the medicine with food, to decrease iron uptake, and drug interactions, as CKD patients often take other medications throughout the day.

Several studies have compared sucroferric oxyhydroxide’s efficacy, safety and tolerability with those of other phosphate-binders and previous trials indicate a similar efficacy in lowering serum phosphate. A Phase 3 study (NCT01324128) comparing sucroferric oxyhydroxide and sevelamer carbonate in dialysis patients found the medicines were both effective, but sucroferric oxyhydroxide had a lower pill burden and better adherence to therapy from patients.

In their review, the authors conclude that “the overall benefit-risk balance of sucroferric oxyhydroxide is deemed to be positive because of the efficacy, safety profile, and only limited potential iron absorption. This iron-based phosphate binder may therefore represent a new good option for the treatment of hyperphosphatemia in CKD patients on dialysis.”