Hyperkalemia is a serious condition that can result in life-threatening cardiac arrhythmias. Patients with compromised renal potassium excretion, primarily patients with chronic kidney disease (CKD), are most at risk of hyperkalemia. Hyperkalemia frequently occurs where the underlying disorder is persistent and generally progressive. Thus, treatment may be needed for long periods of time and/or may need to be repeated. Current options for the ongoing management of recurrent or persistent hyperkalemia have limited utility and include dietary potassium restriction, diuretics, sodium bicarbonate and the cation exchange resins sodium and calcium polystyrene sulfonate.

Until recently, sodium polystyrene sulfonate (KayexalateÆ), approved by the FDA in 1958, was the only medication in the US specifically indicated for the treatment of hyperkalemia. Since effective lowering of serum potassium with sodium polystyrene sulfonate may take hours to days, treatment with this drug alone may not be sufficient to rapidly correct severe hyperkalemia associated with the rapid tissue breakdown or marked hyperkalemia considered to be a medical emergency. Warning and Precautions added to the Kayexelate label in 2009 and 2011 may also limit its use.

Relypsa applied its polymer technology with the intent to design an orally administered, non-absorbed potassium binder with physicochemical characteristics that would provide effective and sustained reductions in serum potassium and with a safety and tolerability profile that would support long term chronic use. VELTASSAÆ (patiromer) for oral suspension was recently approved by FDA for the treatment of hyperkalemia (given its delayed onset of action, it should not be used as an emergency treatment for life-threatening hyperkalemia). The active moiety, patiromer, is a sodium-free, non-absorbed polymer that binds potassium in exchange for calcium in the gastrointestinal tract, increasing fecal potassium excretion and lowering serum potassium levels. A comprehensive nonclinical and clinical testing program was conducted to support the development of the product for its intended use in humans for the treatment of hyperkalemia. The primary objectives of the clinical development program included: the evaluation of safety and efficacy in subjects with underlying conditions that are common causes of hyperkalemia in the clinical setting; a reduction in serum potassium to within the normal range; and an assessment of safety and tolerability, particularly in support of repeated and long term use.

This talk will provide perspectives on the mechanism of action and clinical development program used to develop patiromer from preclinical to use in patients today.