ASN 2010: New Treatment May Reverse the Progression of CKD

Early results from a phase 2b clinical study show that bardoxolone methyl, a novel agent which targets an anti-inflammatory pathway, can reduce the stage of chronic kidney disease (CKD) patients with type 2 diabetes from later stages of the disease to less dangerous earlier stages while improving estimated glomerular filtration rate (eGFR).

Twenty-four-week results were reported Saturday at Renal Week 2010, the American Society of Nephrology 43rd Annual Meeting and Scientific Exposition. Having reached its pre-specified primary endpoint, findings for the randomized year-long trial show that administration of bardoxolone methyl improved CKD manifestations by at least one stage for 59% of the patients. In contrast, only 17% of the study’s placebo group exhibited evidence of CKD stage reversal.

Pablo Pergola, MD, research director for Renal Associates PA and a professor of medicine at the University of Texas Health Science Center in San Antonio, said “Current available treatments can only slow the progression of the disease, but typically do not reverse it. I believe the (week 24) results are fairly clinically significant, and as you can see, the difference between those (bardoxolone) patients and the placebo was highly significant. The patients were able to get out of more advanced disease stages and move over to earlier phases of the disease.”

Reductions in the number of patients in the therapy group with Stage 4 CKD, compared to baseline data, were not matched by similar levels of reduction in the placebo group. Moreover, of those patients in whom the disease stage appeared to progress to more dangerous levels, 14% were in the placebo group versus just 4% in the therapy group.

Bardoxolone methyl was developed by Michael Sporn, a professor of pharmacology and toxicology at Dartmouth Medical School, in conjunction with Abbott and Reata Pharmaceuticals. In clinical process since 2006, the agent targets Nrf2, a novel CKD inflammatory pathway. Previously reported effects include increases in estimated GFR, decreases in serum phosphorus and serum uric acid, and increases in creatinine clearance.

Baseline characteristics of the study’s 227 patients include a mean age of 67 and a mean period of 18 years as a diabetes patient. Seventy-five percent of the participants are diagnosed as obese. Sixty-two percent are Stage 3b CKD patients and 38% are at Stage 4. Mean eGFR for the group is 32 mL/min/1.73m2.

Data show that patients taking the therapy experienced a mean increase in eGFR of more than 10 mL/min/m2. GFT increases occurred steadily until week 12 of the trial, and then leveled off. Placebo patients experienced no change in eGFR. The frequency of adverse events was higher in the bardoxolone methyl group, with muscle spasm reported as the most widely reported side effect.

“We have work to do ahead of us,” said Pergola. “We’ll be analyzing the 52-week data in January of next year. We believe the results merit the initiation of a phase 3 outcome study, the name of which will be BEACON, to be initiated early next year, and will measure important clinical outcomes.”