Lilly and Boehringer Ingelheim Jointly Announce the Recision of U.S. FDA Application for Duloxetine for Treatment of Stress Urinary Incontinence

Companies Confident in SUI Data and Are Evaluating Options


Jan 28, 2005, 00:00 ET from Eli Lilly and Company from ,Boehringer Ingelheim Pharmaceuticals, Inc.

/PRNewswire-FirstCall/ -- Eli Lilly and Company and Boehringer Ingelheim
 Pharmaceuticals, Inc. today jointly announced that Lilly has withdrawn from
 the U.S. FDA's Division of Reproductive and Urologic Drug Products its New
 Drug Application for duloxetine hydrochloride for the treatment of stress
 urinary incontinence (SUI).  This decision was based on discussions with the
 FDA suggesting the agency is not prepared at this time to grant approval for
 duloxetine for the treatment of the SUI patient population based on the data
 package submitted.  The companies will evaluate all options for next steps
 once they have had time to fully understand the FDA's perspective. Ongoing
 clinical trials for duloxetine SUI will continue.
     This action does not affect the marketing status of duloxetine for the
 indications of depression and diabetic peripheral neuropathic pain (DPNP) in
 the United States or the SUI and depression indications outside of the United
     "Despite this decision, we continue to have confidence in duloxetine,
 which is currently available for the treatment of stress urinary incontinence
 in many other countries," said Sidney Taurel, chairman, president and chief
 executive officer, Eli Lilly and Company.
     "We are certainly disappointed with this outcome but are committed to
 exploring our options for duloxetine, as millions of American women who suffer
 from SUI do not currently have a pharmaceutical option to help manage their
 condition," stated Dr. Alessandro Banchi, chairman of the Board of Managing
 Directors of Boehringer Ingelheim.
     Duloxetine for the treatment of SUI, marketed as Yentreve(R) and
 AriClaim(R) outside of the United States, has been deemed safe and effective
 by regulatory authorities that have granted its approval in 27 countries
 throughout the world.
     Duloxetine for the treatment of major depressive disorder and DPNP has
 already been approved by the U.S. FDA as a safe and effective treatment under
 the brand name Cymbalta(R). The European Commission has approved duloxetine
 under the trade names of Cymbalta(R) and Xeristar(R) for major depressive
 episodes.  Throughout the world, the drug is approved in 30 countries for
 major depression.
     About SUI
     SUI is the accidental leakage of urine during physical activities such as
 sneezing, coughing, laughing, lifting or exercising.  It is an embarrassing
 and bothersome medical condition that affects nearly 15 million adult women in
 the United States(1,2) and can have a significant impact on quality of life.
 With nearly twice the prevalence of urge incontinence, SUI is the most common
 form of urinary incontinence among women.(3)  Although common, it is a medical
 condition that is not normal at any age; unfortunately, many women do not seek
 treatment because they are embarrassed, fear surgery, or believe that it is a
 normal part of aging and that nothing can be done about it.  The primary
 causes of SUI are weakness of the urethral sphincter and/or diminished pelvic
 support of the bladder and urethra.  Risk factors include obesity, childbirth,
 chronic coughing, and constipation.(4)
     About Duloxetine
     Based on preclinical studies, duloxetine for SUI is a dual reuptake
 inhibitor and is believed to affect SUI by blocking the reuptake of serotonin
 and norepinephrine in the spinal cord.(3)  The increase in the
 neurotransmitters in turn stimulates increased activity of the pudendal nerve
 that controls the external urethral sphincter.  This stimulation is believed
 to increase contraction of the external urethral sphincter, thereby helping
 prevent accidental urine leakage with physical activity.
     Clinical studies of duloxetine for the treatment of SUI have shown the
 most commonly reported adverse events (incidence of greater than or equal to 5
 percent and significantly more common than placebo) reported by patients
 receiving duloxetine have been nausea, dry mouth, fatigue, insomnia,
 constipation, headache, dizziness, somnolence (drowsiness) and diarrhea.(5)
     About Cymbalta
     Cymbalta (sim-BAWL'-tuh) is indicated in the United States for the
 treatment of major depression and the management of diabetic peripheral
 neuropathic pain, both in adults. As Cymbalta has not been studied in
 children, Lilly discourages its use in those under 18.
     Cymbalta should not be confused with Symbyax(TM) (pronounced SIMM-bee-ax),
 a medicine for bipolar depression also marketed by Lilly. Symbyax is a
 combination of olanzapine, the active ingredient in Zyprexa(R), and
 fluoxetine, the active ingredient in Prozac(R). Symbyax is available in
 capsules of 6 mg/25 mg (olanzapine/fluoxetine), 12 mg/25 mg, 6 mg/50 mg and 12
 mg/50 mg. Cymbalta is available in 20 mg, 30 mg and 60 mg capsules.
     Important Safety Information
     In clinical studies, antidepressants increased the risk of suicidal
 thinking and behavior in children and adolescents with depression and other
 psychiatric disorders.  Anyone considering the use of Cymbalta or any other
 antidepressant in a child or adolescent must balance the risk with the
 clinical need.  Patients who are starting therapy should be observed closely.
 Families and caregivers should discuss with the doctor any observations of
 worsening depression symptoms, suicidal thinking and behavior, or unusual
 changes in behavior.  Cymbalta is not approved for use in patients under the
 age of 18.
     Patients on antidepressants and their families or caregivers should watch
 for worsening depression symptoms, unusual changes in behavior and thoughts of
 suicide, as well as for anxiety, agitation, panic attacks, difficulty
 sleeping, irritability, hostility, aggressiveness, impulsivity, restlessness,
 or extreme hyperactivity.  Call the doctor if you have thoughts of suicide or
 if any of these are severe or occur suddenly.  Be especially observant at the
 beginning of treatment or whenever there is a change in dose.
     Prescription Cymbalta is not for everyone. People who are allergic to
 duloxetine hydrochloride or the other ingredients in Cymbalta should not take
 it.  If you have recently taken a type of antidepressant called a monoamine
 oxidase inhibitor (MAOI), are taking thioridazine or have uncontrolled narrow-
 angle glaucoma, you should not take Cymbalta. Talk with your doctor before
 taking Cymbalta if you have liver or kidney problems, glaucoma or consume
 large quantities of alcohol.  Women who are pregnant should talk with their
 doctor before taking Cymbalta.  Breast feeding while taking Cymbalta is not
     In clinical studies of Cymbalta for depression, the most common side
 effects were nausea, dry mouth, constipation, decreased appetite, fatigue,
 sleepiness, and increased sweating. Cymbalta also is approved for the
 management of neuropathic pain associated with diabetic peripheral neuropathy.
 In clinical studies of Cymbalta in these patients, the most common side
 effects were nausea, sleepiness, dizziness, constipation, dry mouth, increased
 sweating, decreased appetite, and muscle weakness.  In all clinical trials,
 most people were not bothered enough by side effects to stop taking Cymbalta.
 Your doctor may periodically check your blood pressure. Don't stop taking
 Cymbalta without talking to your doctor.
     For full prescribing information, visit
     About Lilly and Boehringer Ingelheim
     In November 2002, Eli Lilly and Company and Boehringer Ingelheim signed a
 global long-term agreement to jointly develop and commercialize duloxetine
 hydrochloride for the treatment of stress urinary incontinence (SUI),
 depression and diabetic peripheral neuropathic pain (DPNP).  This partnership
 covers most countries worldwide with few exceptions. In the U.S., the
 collaboration focuses on SUI and excludes depression and DPNP.
     Eli Lilly and Company
     Lilly, a leading innovation-driven corporation, is developing a growing
 portfolio of first-in-class and 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
     Boehringer Ingelheim Pharmaceuticals, Inc.
     Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, Conn., is
 the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield,
 Conn.) and a member of the Boehringer Ingelheim group of companies.
     The Boehringer Ingelheim group of companies is one of the world's 20
 leading pharmaceutical companies.  Headquartered in Ingelheim, Germany, it
 operates globally with 152 affiliates in 45 countries and more than 34,000
 employees.  Since it was founded in 1885, the family-owned company has been
 committed to researching, developing, manufacturing and marketing novel
 products of high therapeutic value for human and veterinary medicine.
     In 2003, Boehringer Ingelheim posted net U.S. sales of $8.37 billion (7.4
 billion euro), while spending more than one fifth of net sales in its largest
 business segment--prescription medicines--on research and development.
     For more Prescribing Information, please visit
     * Note to Editors:
     Duloxetine for major depressive episodes will be marketed by Lilly and
 Boehringer Ingelheim in all countries included in the partnership under the
 brand name Cymbalta(R), except for Greece, Italy and Spain. In Greece, Italy
 and Spain Lilly will market the product as Cymbalta and Boehringer Ingelheim
 will market the product as Xeristar(R). In the USA the collaboration does not
 include Cymbalta.  In the USA, the collaboration excludes neuroscience
     Duloxetine for stress urinary incontinence will be marketed by Lilly and
 Boehringer Ingelheim in all countries included in the partnership under the
 brand name Yentreve(R), except for Greece, Italy and Spain. In Greece, Italy
 and Spain Lilly will market the product as Yentreve and Boehringer Ingelheim
 will market the product as AriClaim(R).
     This press release contains forward-looking statements about the potential
 of duloxetine for the treatment of stress urinary incontinence and reflects
 Lilly's current beliefs. However, as with any pharmaceutical product under
 development, there are substantial risks and uncertainties in the process of
 development and/or 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
     1.  Diokno A, Burgio K, Fultz N, Kinchen K, Obenchain R, and Bump R.
 Medical and self-care practices reported by women with urinary incontinence.
 Am J Managed Care. 2004;10:69-78. The estimate of STRESS URINARY INCONTINENCE
 prevalence was derived from Diokno et al and based on STRESS URINARY
 INCONTINENCE prevalence as determined by Hampel et al and by Diokno et al.
     2.  US Census 2000 Briefs (Age & Gender), US Department of Commerce Web
     3.  Thor K, Katofiasc M. Effects of duloxetine, a combined serotonin and
 norepinephrine reuptake inhibitor, on central neural control of lower urinary
 tract function in the chloralose-anesthetized female cat. J Pharmacol Exp
 Ther. 1995; 274:1014-1024.
     4.  Fultz NH, Burgio, K, Diokno A, Kinchen K, Obenchain R, and BumpR.
 Burden of stress urinary incontinence for community-dwelling women. Am J
 Obstet Gynecol. 2003; 189: 1275-1282.
     5.  Hurley D, Turner C, Baygani S, Yalcin I, and Viktrup L. Duloxetine for
 stress urinary incontinence: A meta-analysis of safety.  Poster presented at
 the International Federation of Gynaecology and Obstetrics (FIGO) World
 Congress, Santiago, Chile. 2-7 November 2003.

SOURCE Eli Lilly and Company; Boehringer Ingelheim Pharmaceuticals, Inc.