Eli Lilly and Company: Cymbalta Effect on Neuropathic Pain Underscores Mechanism Important for Treating Painful Physical Symptoms of Depression

Business Wire, May 19, 2003

Business Editors/Health/Medical Writers

SAN FRANCISCO--(BUSINESS WIRE)--May 19, 2003

New data show Cymbalta(TM) (duloxetine hydrochloride) significantly reduced pain associated with diabetic neuropathy after one week of treatment and throughout the remainder of the study. The data, presented yesterday at a major psychiatric meeting, complement previous studies in which patients treated with Cymbalta experienced significant improvement on both the emotional and painful physical symptoms of depression versus patients treated with placebo.

In addition to their role in depression, serotonin and norepinephrine are believed to mediate pain perception in the brain and spinal cord pathways. An imbalance of these neurotransmitters may explain why painful physical symptoms affect up to 70 percent of patients with depression. Cymbalta is an investigational serotonin and norepinephrine reuptake inhibitor (SNRI) being studied for the treatment of Major Depressive Disorder.

"We know that both serotonin and norepinephrine are needed to reduce pain. Here, Cymbalta's effects in this pure form of pain further support the compound's balanced dual reuptake action," said Michael Detke, M.D., Ph.D., senior clinical research physician, Eli Lilly and Company. "With Cymbalta in this study, we saw clinically significant responses in more than 60 percent of patients, which is remarkable for this type of study."

"Because vague aches and pains, such as backache, shoulder pain or headaches, are so common in depression, an antidepressant with effects on pain may provide, in theory, a more complete resolution of symptoms among depressed patients," said psychiatrist Maurizio Fava, M.D., director, Depression & Clinical Research Program, Massachusetts General Hospital and Harvard Medical School.

Study highlights include:

-- 64 percent of patients administered Cymbalta 60mg once daily

reported a statistically significant improvement in pain

compared to 47 percent of patients taking the placebo on the

24-Hour Average Pain Severity on a 0-10 self-rating scale

(p=.01). Response was defined as a 30% reduction from

baseline.

-- Significant improvements in pain among patients taking

Cymbalta 60 mg once daily over placebo were seen after one

week of active therapy (p less than .001).

-- Patients on Cymbalta 60 mg once daily also showed an

improvement in secondary measures when compared with patients

administered placebo such as Average Pain Severity as measured

by the Brief Pain Inventory (p=.013), McGill Pain Total Score

(p=.001) and the Brief Pain Inventory Interference General

Activity score (p=.036).

-- Safety and tolerability of Cymbalta 60mg once daily was

favorable with a discontinuation rate due to adverse events of

13.2% versus 5.2% for placebo. Adverse events in the Cymbalta

60mg once daily arm include nausea 16.7% (versus 9.6% on

placebo), dry mouth 7% (versus 6.1% on placebo), constipation

14.9% (versus 3.5% on placebo), dizziness 9.6% (versus 7.0% on

placebo) and somnolence 20.2% (versus 7.8% on placebo).

Method

In a 12-week randomized multi-center double-blind study, patients (N=457) with diabetic neuropathy were randomly given Cymbalta at either 60 mg administered once or twice daily or 20 mg once daily or a placebo. Patients with depression were excluded from the study. Efficacy was assessed by weekly mean scores on the 24-Hour Average Pain Severity on a 0-10 self-rating scale.

Lilly, 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. Additional information about Lilly is available at www.lilly.com.

This press release contains forward-looking statements reflecting Lilly's current beliefs about the potential of the investigational compound duloxetine for the treatment of depression and related physical symptoms. However, as with any pharmaceutical under development, there are substantial risks and uncertainties in the process of development and regulatory review. There is no guarantee that the product will receive regulatory approvals, and any indication for which it is approved will be determined at the discretion of the Food and Drug Administration. There is also no guarantee that the product will prove to be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's filings with the United States Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.