Positive Results from Phase 2 Study of Atrasentan for Treatment of Diabetic Kidney Disease Published in the Journal of the American Society of Nephrology

ABBOTT PARK, Ill., March 4, 2011 /PRNewswire/ -- Results from a Phase 2, 8-week dose-ranging study using low doses of atrasentan in patients with diabetic kidney disease were published this week in the Journal of the American Society of Nephrology. The published 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.

Atrasentan is a highly selective endothelin-A receptor (ETAR) antagonist under investigation as a potential treatment for diabetic kidney disease.

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 (n=23) 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 35% in the 0.25 mg, 0.75 mg and 1.75 mg groups vs. 11% in placebo (P=0.291, P=0.023 and P=0.073, respectively).
• A significantly larger 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 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). Other adverse events that occurred in >5% of patients and at a rate >5% vs. placebo included dizziness, urinary tract infection, headache and hypoglycemia. Due to the small numbers of patients in each treatment group and the low event rates, the significance of these other adverse events is unknown.

"Current standard of care modestly slows the progression of the disease and previous studies with standard of care have shown an association with albuminuria reduction and a slowing of disease progression," 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 early study results suggest that atrasentan may have an additional therapeutic role for albuminuria reduction when added to the current standard of care for patients with type 2 diabetes."

"Chronic kidney disease and diabetic kidney disease are growing healthcare issues. New treatments that could potentially alter the progression of the disease are needed," said James Stolzenbach, Ph.D., divisional vice president, Dyslipidemia and Renal, Abbott. "Abbott looks forward to continued study of atrasentan in longer, outcome-driven clinical trials."

Study Objectives and Design

The study was a double-blind, dose-ranging, placebo-controlled study of 89 diabetic subjects with nephropathy on stable doses of renin-angiotensin system (RAS) inhibitors for >2 months with urinary albumin-to-creatinine ratio (UACR) of 100-3000 mg/g, eGFR >20 mL/min/1.73m2, and NT-pro-BNP <500 pg/mL.  Patients were equally randomized to placebo, atrasentan 0.25, 0.75, or 1.75 mg daily for eight weeks.  The study's primary endpoint was mean change in UACR ratio from baseline to each treatment visit compared to standard of care. The key secondary endpoint was the proportion of subjects achieving at least a 40 percent reduction in final UACR levels from baseline.

About Atrasentan

Atrasentan is an investigational compound belonging to a class of compounds known as selective endothelin-A receptor antagonists, which block the effect of endothelin–l (ET-l), a protein that constricts blood vessels and raises blood pressure that impact kidney functions.  Atrasentan is a highly selective endothelin-A receptor antagonist that is being investigated for its effects in type 2 diabetics with nephropathy.  Atrasentan was discovered and developed by Abbott scientists.

About Chronic Kidney Disease (CKD) and Diabetic Nephropathy

CKD is a highly prevalent condition worldwide, with numbers expected to rise over the next decade. CKD is often under diagnosed due to a lack of symptoms in early stages. Data from the U.S. Renal Data System (USRDS) suggest there has been a 20 percent increase in chronic kidney disease in the United States over the past decade. CKD affects an estimated 26 million Americans.  In addition, half of CKD patients also have diabetes, a percentage that is expected to grow as rates of diabetes increase.  Diabetic CKD patients account for approximately 24 percent of total Medicare diabetes costs. Current treatments modestly slow the progression of CKD, and patients ultimately progress to dialysis and end-stage disease.

Abbott in Renal Care

Abbott has decades of expertise in renal disease across its pharmaceutical, diagnostic and nutritional businesses.  In addition to atrasentan, Abbott has an exclusive collaboration agreement with Reata Pharmaceuticals to develop and commercialize bardoxolone methyl for the treatment of chronic kidney disease outside the U.S.  Abbott also markets other pharmaceuticals and Suplena® and NePro® nutritionals for patients who have CKD or who are on dialysis.  In diagnostics, Abbott offers numerous diagnostic tests for CKD diagnosis and monitoring, point-of-care testing kidney function, and, outside the U.S., a test for urine NGAL (neutrophil gelatinase-associated lipocalin), a novel biomarker that can indicate patients with, or at risk of, acute kidney injury.

About Abbott

Abbott (NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics.  The company employs nearly 90,000 people and markets its products in more than 130 countries.

Abbott's news releases and other information are available on the company's Web site at www.abbott.com.

SOURCE Abbott