Kidney improvement sustained by Abbott drug: study
By Bill Berkrot
NEW YORK (Reuters) - Diabetics with moderate to severe chronic kidney disease showed significant and sustained improvement in kidney function through 52 weeks of treatment with a novel drug being developed by Abbott Laboratories, according to data from a midstage clinical trial.
The oral drug, bardoxolone methyl, is the first medicine to demonstrate improvement in kidney function in patients with the deadly disease and could delay the need for expensive and inconvenient kidney dialysis, researchers said.
Current treatments, which are primarily blood pressure control medicines, have only been able to slow progression of chronic kidney disease.
"This is totally unique in my 20-plus years of treating patients with chronic kidney disease. There's nothing out there that increases kidney function," Dr. David Warnock, who presented the data at a European kidney meeting in Prague on Friday, said in a telephone interview.
"The important improvement we saw at the primary endpoint of week 24 is persisting and sustained throughout the entire 52 weeks of treatment," Warnock added.
Bardoxolone showed statistically significant kidney improvement compared with placebo at all three doses tested -- 150 milligrams, 75mg and 25mg -- researchers said.
Based on the results of the 227-patient study, Abbott and its partner, privately-held Reata Pharmaceuticals, which discovered the drug, selected the 75mg dose for a recently initiated pivotal Phase III trial.
Bardoxolone is the first drug from a new class called antioxidant inflammatory modulators that work by suppressing inflammation, researchers said.
Patients in the midstage trial had Type 2 diabetes and moderate to severe chronic kidney disease, defined by an estimated glomerular filtration rate (eGFR) of 20 to 45. A person with normally functioning kidneys has an eGFR -- a common measure of kidney function -- of 100.
The Abbott drug raised eGFR by nearly 30 percent compared with placebo at the two higher doses. Those who got the 75 mg dose had an average eGFR improvement of 10.5, while 150mg patients saw a 9.5 eGFR improvement.
About 21 percent of placebo patients suffered a significant loss of kidney function (more than 25 percent) over the course of the 52 weeks, which is typical for the progressive disease, researchers said.
That compared with just 9 percent with significant kidney function loss for bardoxolone patients, meaning 91 percent experienced beneficial effects on kidney function, Warnock explained.
"What we have now today is a very promising data set that would suggest there is a possibility we can actually improve kidney function even in patients who have far advanced severe chronic kidney disease," said Warnock, a professor of medicine in the division of nephrology at the University of Alabama in Birmingham.
"If this is confirmed as being clinically significant in terms of benefit to these patients, the prospects are very, very exciting," he added.
The 1,600-subject Phase III trial will determine whether the new drug can delay progression to dialysis or cardiovascular death among very high risk kidney patients with diabetes.
The most common adverse side effect seen with bardoxolone methyl included muscle spasm, transient elevations in liver enzymes and nausea.
Most of the side effects seen in the first 24 weeks of treatment had moderated or subsided during the latter portion of the study, Warnock said.
"The adverse effect profile was something that we're quite comfortable with, and we feel comfortable moving forward now with the definitive Phase III outcomes study," he said.
An estimated 20 million Americans have chronic kidney disease; about 500,000 are on dialysis or in need of transplants, according to the National Kidney Foundation.
Diabetes is the most common cause of end stage renal disease, which progresses to a need for kidney dialysis and death.
"To keep patients off the dialysis machine will be a huge impact in terms of quality of life," Warnock said.
In addition, end stage renal disease patients consume a huge portion of the Medicare budget compared to their numbers, he said.
"If we can keep people off dialysis, which costs about $75,000 a year, that would be just absolutely huge," he said.
Results of the Phase II study presented in Prague are also being published in the New England Journal of Medicine.
(Reporting by Bill Berkrot; editing by John Wallace)