Data Presented at International Diabetes Meeting Reveals Lilly's Ruboxistaurin Mesylate May Delay Progression of Diabetic Macular Edema.

Business Editors/Health/Medical Writers

PARIS--(BUSINESS WIRE)--Aug. 25, 2003

Diabetic macular edema is the leading cause

of reduced vision in adults

Eli Lilly & Company's (NYSE:LLY) investigational compound, ruboxistaurin (PKC Beta Inhibitor) mesylate, may delay the progression of diabetic macular edema in patients with mild to moderate nonproliferative diabetic retinopathy receiving the highest dosage of ruboxistaurin, according to results of a multicenter trial presented today during the 18th International Diabetes Federation (IDF) meeting.

Diabetic macular edema is an important complication of diabetic retinopathy, a disease of the small blood vessels in the retina of the eye. Diabetic macular edema is characterized by retinal thickening or fluid leakage near the center of the retina, and is a significant cause of vision loss in people with diabetes. Diabetic macular edema occurs in almost 30 percent of people who have had diabetes for 20 years or more.

"We are very encouraged to see that ruboxistaurin may prevent the development of center-threatening diabetic macular edema, thus delaying the progression of diabetic macular edema in these patients," commented Louis Vignati, M.D., medical director for the ruboxistaurin effort at Lilly. "Based on the trial outcome, additional phase 3 trials will further explore ruboxistaurin's effect on delaying the progression of diabetic macular edema."

Study Results

The PKC Beta Inhibitor Diabetic Macular Edema (PKC-DMES) trial was a multi-center, multi-national, double-masked, placebo-controlled trial, with patients followed for up to 52 months. The trial included 686 patients with diabetic macular edema and mild to moderate nonproliferative diabetic retinopathy. Ruboxistaurin, when given at 32mg, displayed a trend (p=0.041) towards a positive effect on the secondary outcome of occurrence of diabetic macular edema involving or imminently threatening the center of the macula. When patients with poor glycemic control at baseline were excluded (defined as a hemoglobin A1C greater than or equal to 10 percent), ruboxistaurin displayed a borderline positive effect (p=0.019) on the occurrence of diabetic macular edema involving or imminently threatening the center of the macula.

Ruboxistaurin is being studied as a possible treatment for diabetic peripheral neuropathy (damage to the nerves), diabetic retinopathy (including diabetic macular edema) and diabetic nephropathy (damage to the kidneys), the three major diabetic microvascular complications. Because type 2 diabetes is often not diagnosed until years after onset, many patients already have diabetic microvascular complications at diagnosis; 3 of 4 patients with diabetes develop at least one complication within 15 years of diagnosis.

Eli Lilly and Company, a leading innovation driven corporation, is developing a growing portfolio of best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers -- through medicines and information -- for some of the world's most urgent medical needs.

This news release contains forward-looking statements that reflect management's current beliefs about the potential for ruboxistaurin (PKC Beta Inhibitor, LY333531) mesylate in the treatment of diabetic retinopathy and diabetic macular edema. However, as with any pharmaceutical under development, there are significant risks and uncertainties in the process of development and regulatory review. The product has not yet been proven safe and effective. There are no guarantees that the product will receive necessary regulatory approvals or prove to be commercially successful. For additional information about the factors that affect the company's business, see the company's filings with the United States Securities and Exchange Commission. The company undertakes no duty to update forward-looking statements.