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

By Abbott, PRNE
Sunday, November 21, 2010

ABBOTT PARK, Illinois, November 22, 2010 - 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

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

Media, Tracy Sorrentino, +1-847-937-8712; or Financial, Larry Peepo, +1-847-935-6722, both of Abbott

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