Two drugs found effective in treating hyperkalemia

By Gene Emery

(Reuters Health) - Two experimental oral drugs can reduce hyperkalemia, according to separate studies financed by the manufacturers and released Friday by the New England Journal of Medicine.

The drugs are sodium zirconium cyclosilicate (also known as ZS-9 and being developed by ZS Pharma) and patriomer (formerly known as RLY5016 and developed by Relypsa). Both drugs are designed to treat hyperkalemia by binding to potassium as they travel through the gut.

If the drugs are approved -- and longer-term tests are needed -- they could change the way doctors treat kidney disease and heart failure.

That's because hyperkalemia is a potentially deadly side effect when doctors use renin-angiotensin-aldosterone system (RAAS) inhibitors for kidney and heart problems.

"Doctors are paranoid about hyperkalemic death when they use these kidney- and heart- protective drugs. So they won't use them, or they use them in much lower doses than they should," said Dr. Matthew Weir of the University of Maryland School of Medicine and chief author of the patiromer study.

The new drugs should alleviate some of that concern, Dr. Weir told Reuters Health in a telephone interview.

Dr. David Packham of the University of Melbourne, chief author of the ZS-9 study, foresees a similar benefit for the drug he tested.

"Because the effect can be maintained, in this case for 14 days, it has the potential for being an enabling therapy that enables you to keep patients on treatments that benefit them that often have to be reduced in dose because of hyperkalemia," he said by phone.

A smaller study on ZS-9 was reported this week in the Journal of the American Medical Association.

The ZS-9 study by Dr. Packham and his colleagues involved multiple stages and doses that were tested on 753 volunteers from the U.S., Australia and South Africa. The patients were kept on their usual diabetes and kidney medications, and told not to change their diet.

It took a dose of 2.5 grams or higher three times daily with meals for as long as 48 hours for doctors to see blood potassium fall to normal levels. The levels stayed in the safe zone when patients stayed on the treatment for two weeks.

Among patients who responded well to the drug, all were cut back to once-a-day therapy and some were switched to placebo. In placebo recipients, potassium levels rose once again.

"What this does is reliably and very rapidly -- within 48 hours -- dramatically reduce potassium levels," said Dr. Packham. "You could see where the patients who were changed to placebo went back up to their previous potassium levels over the 14-day period, whereas the levels were maintained in the patients who were kept on ZS-9. And when they were taken off, the levels went back up again. It was very, very clear."

"The drug was equally effective across various subgroups, including patients with a combination of heart failure, chronic kidney disease, and diabetes," the researchers concluded.

"I think it will become the standard for treatment for acute hyperkalemia," Dr. Packham said.

Dr. Weir expressed a similar sentiment for patiromer.

That test, involving 237 patients with high potassium levels who were getting RAAS inhibitors for their long-term kidney disease, "is quite a definitive study," he said. "It's a study done exclusively in people with chronic kidney disease receiving the lone therapy we know of that slows the progression of kidney disease."

After four weeks of patiromer therapy, potassium levels had fallen into the normal range for 76% of the patients, some of whom had received a higher dose of the drug based on the excessiveness of their potassium levels. All had been advised to follow a low-potassium diet.

Among 52 volunteers who were then taken off the drug and given a placebo instead, potassium returned to unacceptably high levels in 60%. Yet among the 55 patients who were kept on the drug, only 15% redeveloped hyperkalemia at the eight-week mark.

At least one side effect occurred in 47% of people on the drug, a rate that was similar among placebo recipients. The most common side effect was mild-to-moderate constipation, which surfaced in 11%. Potassium levels dropped too far in 3%.

With ZS-9, at least one side effect was reported at some point in 25.1% getting the drug and 24.5% receiving placebo. The most common side effect was diarrhea, seen in 1.8% of patients taking the drug and 2.5% with placebo. In two patients, potassium levels dropped too far, but the effect was temporary.

Dr. Weir said the two drugs rely on different mechanisms, may have different side effects and have yet to be pitted against each other in a study. "But I think both are going to be heads and tails above existing therapies."

SOURCES: http://bit.ly/1xc4ZLl and http://bit.ly/1F8Zr8V

N Engl J Med 2014

(c) Copyright Thomson Reuters 2014. Click For Restrictions - http://about.reuters.com/fulllegal.asp