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 INDIANAPOLIS, Ind. and RIDGEFIELD, Conn., Jan. 28
/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has withdrawn from the U.S. FDA's Division of Reproductive and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
States. "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 recommended.
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
http://www.cymbalta.com/. 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 http://www.lilly.com/. 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
http://www.boehringer-ingelheim.com/. * 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
indications. 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). P-LLY 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 statements. REFERENCES
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 site. 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. (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO
http://www.newscom.com/cgi-bin/prnh/20040122/BILOGO )
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO
http://www.newscom.com/cgi-bin/prnh/20040122/BILOGO DATASOURCE: Eli
Lilly and Company; Boehringer Ingelheim Pharmaceuticals, Inc.
CONTACT: Tammy Hull of Lilly, +1-317-651-9116, ; or Marybeth
McGuire of Boehringer Ingelheim, +1-203-798-4801,
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