Phase III trial shows effectiveness of metabolic acidosis drug
Chronic kidney disease—which affects about 14 percent of Americans—kills more people each year than breast or prostate cancer. People with chronic kidney disease commonly develop a condition called metabolic acidosis, meaning, there is too much acid in bodily fluids because their diseased kidneys are less able to remove accumulating acid from body fluids and have it leave the body in the urine.
Metabolic acidosis is currently treated in two ways. Most commonly, clinicians prescribe drugs like sodium bicarbonate (baking soda) that are absorbed from the gut into the blood to neutralize accumulated acid. Alternatively, clinicians prescribe a diet that limits acid accumulation in body fluids.
A new drug candidate, called veverimer, may treat metabolic acidosis safely and effectively, and do so by removing accumulated acid from the gut without entering the bloodstream, according to a phase III clinical trial, for which results were published in The Lancet.
Donald E. Wesson, MD, professor at the Texas A&M College of Medicine and nephrologist by medical specialty, leveraged his years of research regarding metabolic acidosis to work with other investigators to help develop the drug and design the research to test its effectiveness. In the first long-term, randomized, multicenter, blinded, placebo-controlled clinical trial to evaluate the treatment of metabolic acidosis in patients with chronic kidney disease, veverimer, produced by the pharmaceutical company Tricida, Inc., proved more effective than a placebo at treating the condition.
“In later stages of chronic kidney disease, metabolic acidosis may further complicate the condition, resulting in muscle wasting, bone loss and further progression of kidney disease,” said Wesson, the lead author of the paper in The Lancet. “The importance of metabolic acidosis as both a serious complication of chronic kidney disease and an underlying cause of chronic kidney disease progression has been underrecognized and markedly undertreated.”
The drug works by removing hydrochloric acid from the gastrointestinal tract. The study followed patients for an initial 12 weeks, then in a 40-week extension study. In those 40 weeks, only 2 percent of people on veverimer had serious adverse events compared with 5 percent of those taking a placebo. Therefore, the patients were on the drug for a full year.
Phase III clinical trials establish safety and effectiveness of new drug candidates. Because they are longer and involve more patients, they are better able to detect side effects than earlier trials are. The next step is to submit a new drug application to the U.S. Food and Drug Administration for approval.
“Metabolic acidosis is common, harmful and must be treated to help spare patients the untoward consequences of chronic kidney disease. Veverimer offers the hope to treat this devastating complication safely and effectively,” Wesson said.