Abbott announced positive results from a Phase 2 dose-ranging study of atrasentan, a highly selective endothelin A receptor antagonist in development to help slow chronic kidney disease (CKD) progression in patients with type 2 diabetic nephropathy (diabetic kidney disease). Study results suggest that atrasentan, used in conjunction with renin-angiotensin system (RAS) inhibitors, may reduce albuminuria (presence of protein in urine) for patients with type 2 diabetes. Albuminuria is the main sign of diabetic nephropathy and as kidney function decreases, the level of albumin in the urine rises. Results were presented at the annual American Society of Nephrology meeting in Denver, Colorado.
Key findings from the 8-week study of three doses of atrasentan (0.25 mg, n=22; 0.75 mg, n=22; 1.75 mg, n=22) vs. placebo were:
• Atrasentan significantly reduced urine albumin-to-creatinine ratio (UACR) in the 0.75 mg and 1.75 mg groups vs. placebo (P=0.001 and P=0.011 by repeated measures, respectively). The 0.25 mg dose had no significant effect
• Reduction from baseline to final UACR was 21%, 42%, and 34% in the 0.25 mg, 0.75 mg and 1.75 mg groups vs. 11% in placebo (P=0.292, P=0.023 and P=0.080, respectively)
• A statistically significant proportion of subjects achieved >40% reduction in UACR from baseline in the 0.75 mg group vs. placebo (50% vs. 17% respectively, P=0.029). The proportion of patients in the 0.25 mg and 1.75 mg groups (30% and 38% respectively) did not reach statistical significance.
• Peripheral edema (primarily mild) was the most common adverse event (14%, 18% and 46% for 0.25, 0.75 and 1.75 mg with p=0.007 for 1.75 mg vs. 9% in placebo)
“Several large clinical trials with RAS inhibitors have demonstrated that reductions in albuminuria are associated with a delay in the progression of diabetic nephropathy,” said Donald E. Kohan, M.D., Ph.D., Professor of Medicine, Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah and lead investigator for the study. “These study results are encouraging and suggest that atrasentan may have an additional therapeutic role for albuminuria reduction on top of the current standard of care for patients with type 2 diabetes.”
“The impact of chronic kidney disease is a growing global public health concern but few advancements in treatment have been made in the last decade that positively affect outcomes for patients with this progressive disease,” said James Stolzenbach, Ph.D., divisional vice president, Dyslipidemia and Renal, Abbott. “Longer, outcome-driven clinical trials are needed to establish the safety and efficacy of atrasentan in diabetic nephropathy, but we are encouraged by the findings from this study and look forward to further evaluating atrasentan as a candidate for treating this type of chronic kidney disease.”
Date: November 22, 2010