Data Show Lilly's Duloxetine Significantly Reduced the Frequency of Stress Urinary Incontinence Episodes


INDIANAPOLIS--(BW HealthWire)--July 17, 2002--

Potential for the first pharmaceutical treatment to reduce incontinence episode frequency and improve quality of life for stress

urinary incontinence sufferers

Women with stress urinary incontinence using duloxetine experienced significant reductions in the frequency of incontinence episodes and a significant improvement in quality of life compared to women taking placebo, according to a study published in the July issue of the American Journal of Obstetrics and Gynecology (AJOG).

Stress urinary incontinence affects one in three American women(1); it is the involuntary leakage of urine brought on by "stress" or pressure upon the bladder, as a result of laughing, coughing, sneezing, lifting, or exercise. If further studies confirm these data, and if it is approved for use by regulatory agencies, duloxetine could become the first pharmaceutical treatment indicated to reduce the frequency of stress urinary incontinence episodes.

Duloxetine 80mg, taken at 40 mg twice a day, reduced the frequency of incontinence episodes by 64 to 100 percent in half of the women in the duloxetine arm (n= 140) of the study, compared with a 41% median reduction seen in the placebo group. Duloxetine also demonstrated a similar reduction in incontinence episode frequency among a subset of 163 women with more severe incontinence (those experiencing at least 14 incontinence episodes/week). Despite the increased severity of their condition, these subjects, achieved the same reduction in incontinence episode frequency (IEF) with duloxetine as women with less severe incontinence, at the 80mg dose.

"These data are very encouraging for women and physicians alike and provide evidence for the potential of duloxetine as a future pharmaceutical treatment for stress urinary incontinence," said Dr. Peggy Norton, lead clinical trial investigator and associate professor, Department of Obstetrics and Gynecology at the University of Utah in Salt Lake City. "Current treatment options are limited to surgery, devices and pelvic muscle strengthening exercises. If eventually approved, duloxetine could be the first drug therapy indicated for the treatment of stress urinary incontinence, offering a new treatment option for millions of women with the condition."

In this study, patients on duloxetine also reported improvements on scales used to measure effects on their quality of life. Patients responded to a condition-specific questionnaire designed to measure improvement in their condition. Forty-four percent of those taking duloxetine 80mg reported feeling "very much better" or "much better," compared with 27% reporting the same on placebo.

Safety

Duloxetine was generally well tolerated. According to the study authors, none of the adverse events reported, which were related to the study drug, were considered to be clinically severe. Nausea was the most commonly experienced event, and was reported by 13% of patients taking 80mg daily of duloxetine, compared with 2% taking placebo. Only 4 percent of patients taking 80 mg daily of duloxetine stopped taking the drug, compared with 0.7% taking placebo.

About Lilly's duloxetine

Duloxetine is a selective reuptake inhibitor of the neurotransmitters serotonin and norepinephrine (SNRI). Duloxetine is believed to affect stress urinary incontinence by blocking the reuptake of serotonin and norepinephrine in the spinal cord, which in turn stimulates increased activity of the pudendal nerve. Increased activity of the pudendal nerve is believed to increase contractions of the urethral sphincter at the opening of the bladder, thereby helping to prevent accidental urine leakage.

Lilly is also studying the duloxetine compound for the treatment of depression. The company filed a New Drug Application with the Food and Drug Administration for this indication in late 2001.

Study methodology

The Phase II data are derived from a double blind, randomized, placebo-control clinical trial conducted at 48 centers in the United States, among 553 women aged 18-65. All women had a predominant symptom of stress urinary incontinence of a least four episodes per week, for up to three months. The primary measure used by researchers focused on decreases in the incontinence episode frequency that were recorded real-time by patient diaries. Additional measures included the Patient Global Impression of Improvement (PGI-I) Scale, and an Incontinence Quality of Life (I-QOL) Questionnaire.

About Stress Urinary Incontinence

Stress urinary incontinence is the most common form of urinary incontinence among women around the world. In the United States alone it affects one in three(2) women over the age of 18 years - approximately 30 million women(3). Many women who would like relief from their stress incontinence do not actively seek treatment for the condition or discuss it with their physicians due to embarrassment, stigma, a fear of surgery, or a belief that the condition is a normal part of aging.

Stress urinary incontinence is the involuntary leakage of urine brought on by "stress" or pressure upon the bladder, as a result of laughing, coughing, sneezing, lifting, or exercise. Leakage occurs because the muscles and tissues that work to hold urine in the bladder during physical activity become weak or damaged and are unable to remain closed when bladder pressure increases suddenly, as with a sneeze.

Eli Lilly and Company

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 on www.lilly.com.
This press release contains forward-looking statements about the potential of the investigational compound duloxetine in treating stress urinary incontinence that reflect management's current beliefs. However, as with any pharmaceutical under development, there are risks and uncertainties in the process of development and regulatory review. There are no guarantees that future clinical trials will confirm the preliminary results reported in this release or that the product will receive regulatory approvals or prove to be commercially successful. For further discussion of these and other risks and uncertainties, see Exhibit 99 to the most recent Form 10-Q filed with the SEC in May 2002.

(1) National Association for Continence, SUI Survey, May 2002

(2) ibid

(3) Estimated that 29.5 million women have SUI in pure or mixed

forms, based on 2000 US census bureau figures and incontinence

prevalence rate of 35% as cited in Hampel C, Wienhold D,

Benken N, Eggersmann C, Thuroff. Definition of overactive

bladder and epidemiology of urinary incontinence. Urol

1997:50(S6A):4-14

CONTACT:

Eli Lilly and Company

Anne Griffin, 317/276-3254

SOURCE: Eli Lilly and Company