A year-long study of more than 300 patients with hyperkalemia, hypertension, type 2 diabetes, and chronic kidney disease found that the investigational drug Patiromer, made by Relypsa, Inc. can reduce elevated blood-potassium levels.
Patiromer, given in this trial at one of four doses based on disease severity, returned blood potassium levels to normal when measured at four weeks and kept them under control for one year, the length of the trial.
George L. Bakris, MD, of University of Chicago Medicine, Chicago, and colleagues randomly assigned 306 outpatients with type 2 diabetes and an elevated serum potassium level to 1 of 3 starting doses of patiromer twice daily. All patients received renin-angiotensin-aldosterone system (RAAS) inhibitors prior to and during study treatment. The phase 2 trial, known as AMETHYST-DN, was conducted at 48 sites in Europe from June 2011 to June 2013.
“This is a significant advance, a huge deal,” said Bakris. “It affects everyone with stage 4 or 5 chronic kidney disease, almost 1 million people in the United States.”
The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of Oct. 21, 2015. The AMETHYST-DN trial was among eight clinical trials included in the NDA submitted to the FDA for Patiromer FOS
The study, published July 14, 2015, in The Journal of the American Medical Association, is the first to follow patients taking patiromer for more than a few weeks.
In patients with mild or moderate hyperkalemia, patiromer for oral suspension decreased serum potassium levels within 48 hours. For most of those patients, potassium levels remained within the target range at every scheduled visit for the next year. When patients stopped taking the medication, potassium levels in the blood began to increase within three days and hyperkalemia recurred within eight weeks.
The only alternative is a 50-year-old drug that is “difficult to take, poorly tolerated and unpredictable,” Bakris said. “Most patients won’t take it.”
Patients most at risk are those with chronic kidney disease combined with diabetes and hypertension or heart failure. About 10 percent of patients who take renin-angiotensin-aldosterone system (RAAS) inhibitors, which slow the progression of kidney disease, develop hyperkalemia within a year.
Patiromer is made of small smooth spherical beads, about one-tenth of a millimeter in diameter—the size of a typical dust particle. When mixed with a few tablespoons of water and swallowed, these particles attach themselves to potassium ions in the lower part of the colon, where the concentration of free potassium is the highest. The potassium-packed beads are then excreted.
The findings “have the potential to fundamentally change the current treatment approach to hyperkalemia,” according to an accompanying editorial by nephrologist Wolfgang Winklemayer, MD, ScD, of Baylor College of Medicine. The novelty of the study, he added, “lies in the secondary results.” Potassium levels remained essentially stable throughout the maintenance phase, but after the end of the study, “potassium concentrations increased quickly and significantly, once again.”