Abbott Announces Positive Results from Phase 2 Study of Low Dose Atrasentan for Treatment of Diabetic Kidney Disease

Abbott (NYSE: ABT) today 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.”

Study Objectives and Design

The study was a double-blind, dose-ranging, placebo-controlled study of 89 subjects with diabetic 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/1.73m squared, 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. The secondary endpoint was measured as 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 shows promise in targeting the effect of endothelin in diabetic 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 30 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(R) and NePro(R) 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 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 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.