BOTOX® (onabotulinumtoxinA) Receives U.S. Food and Drug Administration Approval for the Treatment of Overactive Bladder for Adults Who Have an Inadequate Response to or Are Intolerant of an Anticholinergic Medication

Fri Jan 18, 2013 5:00pm EST

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BOTOX Demonstrates Efficacy in Reducing Urinary Leakage Episodes
IRVINE, Calif.--(Business Wire)--
Allergan, Inc. (NYSE:AGN) announced today that the U.S. Food and Drug
Administration (FDA) has approved BOTOX® (onabotulinumtoxinA) for the treatment
of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency
and frequency in adults who have had an inadequate response to or are intolerant
of an anticholinergic medication. In two double-blind, randomized, multi-center,
placebo-controlled 24-week clinical trials among adults with overactive bladder
who had not been adequately managed with anticholinergic treatments, BOTOX®
reduced daily urinary incontinence (leakage) episodes as compared to placebo by
50 percent or more by week 12 (reduction of 2.5 episodes from baseline of 5.5
episodes in one study and reduction of 3 episodes from baseline of 5.5 episodes
in the second study for those treated with BOTOX vs. a reduction of 0.9 episodes
from a baseline of 5.1 episodes in one study and a reduction of 1.1 episodes
from a baseline of 5.7 episodes in the second study for those treated with
placebo).1

"Allergan has a long-standing commitment to study the potential of BOTOX to
treat a number of different medical conditions," said Scott Whitcup, M.D.,
Allergan`s Executive Vice President, Research and Development, Chief Scientific
Officer. "With today`s approval, BOTOX is now approved for 26 different
indications in more than 85 countries. Most importantly, today`s FDA approval is
a milestone in the treatment of this burdensome condition and will provide a
novel option for urologists and their OAB patients." 

While the exact cause is often unknown, OAB is a medical condition that results
in an uncontrolled urge to urinate, frequent urination and, in many patients,
uncontrollable leakage of urine. In the United States, an estimated 14.7 million
adults experience symptoms of OAB with urinary incontinence (unexpected leakage
of urine).2 Anticholinergics, which are often prescribed as pills, are used by
approximately 3.3 million Americans with OAB, with or without urinary
incontinence, to manage their condition.3 It is estimated, however, that greater
than 50 percent of these patients stop taking at least one oral medication
within 12 months, likely due to an inadequate response to, or intolerance of,
the medication.4

"Overactive bladder can be a difficult condition to treat as there have been
limited options for patients when currently available medications have failed to
provide them with adequate relief," said Dr. Victor Nitti*, Vice Chairman,
Department of Urology and Director of Female Pelvic Medicine and Reconstructive
Surgery at NYU Langone Medical Center. "With the approval of BOTOX, we have a
new treatment option to offer these patients that has demonstrated efficacy in
reducing urinary leakage and other symptoms of OAB with the effect lasting up to
six months." 

The median duration for efficacy with BOTOX at reducing urinary leakage and
other symptoms of OAB in the two clinical studies was 135-168 days compared to
88-92 days with placebo based on qualification for retreatment. To qualify for
retreatment, at least 12 weeks must have passed since the prior treatment,
post-void residual urine volume must have been less than 200 mL and patients
must have reported at least two urinary incontinence episodes over three days.
BOTOX treatment relieves OAB symptoms by temporarily calming muscle contractions
by blocking the transmission of nerve impulses to the bladder muscle. 

OAB Clinical Development Program
The FDA approval of BOTOX was based on safety and efficacy data from two
double-blind, randomized, multi-center, placebo-controlled 24-week clinical
studies of 1,105 adult patients whose OAB symptoms had not been adequately
managed with anticholinergic therapy, either due to lack of efficacy or
intolerance of the medication. To qualify for the study, patients had to have
symptoms of OAB with symptoms of urge urinary incontinence, urgency and
frequency, and experience a minimum of three urinary urgency leakage
(incontinence) episodes and at least 24 urination episodes (micturitions) over a
three-day timeframe. Patients in the studies were randomized to receive
physician-administered treatment with 100 units of BOTOX neurotoxin (n=557) or
placebo (n=548) injected directly into the detrusor (bladder) muscle. Patients
were treated in the physician`s office and received a local anesthetic, with or
without sedation, to numb the bladder prior to treatment with BOTOX or placebo. 

In both clinical trials, patients treated with BOTOX experienced a reduction of
50% or more in the frequency of daily urinary incontinence episodes from
baseline compared to placebo at week 12 (reduction of 2.5 episodes from baseline
of 5.5 episodes in one study and reduction of 3 episodes from baseline of 5.5
episodes in the second study for those treated with BOTOX vs. a reduction of 0.9
episodes from a baseline of 5.1 episodes in one study and a reduction of 1.1
episodes from a baseline of 5.7 episodes in the second study for those treated
with placebo).1 In addition, approximately three times as many patients treated
with BOTOX in the clinical studies achieved a complete elimination of their
leakage episodes as compared to placebo (22.9% and 31.4% achieved complete
continence with BOTOX vs. 6.5% and 10.3% with placebo at week 12 in the two
clinical trials).5 Improvements in other symptoms of overactive bladder,
including urge to urinate, frequency of urination and the amount of urine voided
also occurred with BOTOX treatment compared to placebo at week 12. 

In the clinical studies, the most frequently reported adverse reactions within
12 weeks of receiving BOTOX injections included urinary tract infection (18% vs.
6% with placebo), dysuria (9% vs. 7% with placebo), which means painful or
difficult urination; and urinary retention (6.5% vs. 0.4% with placebo), which
is a temporary inability to fully empty the bladder requiring the use of a
disposable self-catheter. 

About BOTOX (onabotulinumtoxinA)
BOTOX is a prescription-only medical product that contains tiny amounts of a
highly purified botulinum toxin protein refined from the bacterium, Clostridium
botulinum. The BOTOX formula contains auxiliary proteins that stabilize the core
toxin in BOTOX from degradation. When injected at doses approved by the FDA into
a specific muscle or gland, BOTOX neurotoxin is expected to act locally to
produce a safe and effective result, usually lasting between three to ten months
depending on the approved indication and on the individual patient. 

BOTOX was first approved by the FDA more than 22 years ago for the treatment of
strabismus and blepharospasm, two eye muscle disorders, making it the first
botulinum toxin type A product approved in the world. Today, BOTOX neurotoxin is
approved to treat a total of eight medical conditions in the United States,
including the abnormal head position and neck pain that happens with cervical
dystonia (CD) in adults; symptoms of severe underarm sweating (severe primary
axillary hyperhidrosis) when medicines used on the skin (topical) do not work
well enough; for the treatment of increased muscle stiffness in elbow, wrist,
and finger muscles in adult patients with upper limb spasticity; for the
prophylactic treatment of headaches in adults with Chronic Migraine, a distinct
and severe neurological disorder characterized by patients who have a history of
migraine and suffer from headaches on 15 or more days per month with headaches
lasting four hours a day or longer; for the treatment of urinary incontinence
due to detrusor overactivity associated with a neurologic condition (e.g. spinal
cord injury [SCI], multiple sclerosis [MS]) in adults who have an inadequate
response to or are intolerant of an anticholinergic medication; and for the
treatment of overactive bladder (OAB) with symptoms of urge urinary
incontinence, urgency and frequency in adults who have had an inadequate
response to or are intolerant of an anticholinergic medication. 

In addition to its therapeutic uses, the same formulation of BOTOX with dosing
specific to moderate to severe glabellar lines was approved by the FDA in 2002
under the trade name BOTOX Cosmetic (onabotulinumtoxinA). BOTOX Cosmetic is
indicated for the temporary improvement in the appearance of moderate to severe
glabellar lines (frown lines between the eyebrows) associated with corrugators
and/or procerus muscle activity in adult patients up to 65 years of age. 

Since its first approval in 1989, BOTOX has been recognized by regulatory
authorities worldwide as an effective treatment for 26 different indications in
approximately 85 countries, benefiting millions of patients worldwide. 

In addition to the more than 22 years of clinical experience, the safety and
efficacy of BOTOX have been well-established in approximately 65 randomized,
placebo-controlled clinical trials and in approximately 15,000 patients treated
with BOTOX and BOTOX Cosmetic in Allergan`s clinical trials.6 Worldwide,
approximately 35 million vials of BOTOX and BOTOX Cosmetic have been distributed
over the past 21 years (1990-2011).7

With approximately 2,500 articles on BOTOX and BOTOX Cosmetic in scientific and
medical journals,8 BOTOX neurotoxin is one of the most widely researched
medicines in the world. 

BOTOX (onabotulinumtoxinA) & BOTOX Cosmetic (onabotulinumtoxinA) Important
Information

Indications
BOTOX is a prescription medicine that is injected into muscles and used:

* to treat overactive bladder symptoms such as a strong need to urinate with
leaking or wetting accidents (urge urinary incontinence), a strong need to
urinate right away (urgency), and urinating often (frequency) in adults 18 years
and older when another type of medicine (anticholinergic) does not work well
enough or cannot be taken. 
* to treat leakage of urine (incontinence) in adults 18 years and older with
overactive bladder due to neurologic disease who still have leakage or cannot
tolerate the side effects after trying an anticholinergic medication 
* to prevent headaches in adults with chronic migraine who have 15 or more days
each month with headache lasting 4 or more hours each day in people 18 years or
older 
* to treat increased muscle stiffness in elbow, wrist, and finger muscles in
people 18 years and older with upper limb spasticity 
* to treat the abnormal head position and neck pain that happens with cervical
dystonia (CD) in people 16 years and older 
* to treat certain types of eye muscle problems (strabismus) or abnormal spasm
of the eyelids (blepharospasm) in people 12 years and older

BOTOX is also injected into the skin to treat the symptoms of severe underarm
sweating (severe primary axillary hyperhidrosis) when medicines used on the skin
(topical) do not work well enough in people 18 years and older. 

BOTOX Cosmeticis a prescription medicine that is injected into muscles and used
to improve the look of moderate to severe frown lines between the eyebrows
(glabellar lines) in people 18 to 65 years of age for a short period of time
(temporary). 

It is not known whether BOTOXand BOTOX Cosmetic is safe or effective to prevent
headaches in patients with migraine who have 14 or fewer headache days each
month (episodic migraine). 

It is not known whether BOTOXand BOTOX Cosmetic is safe or effective to treat
increased stiffness in upper-limb muscles other than those in the elbow, wrist,
and fingers, or to treat increased stiffness in lower-limb muscles. BOTOX has
not been shown to help people perform task-specific functions with their upper
limbs or increase movement in joints that are permanently fixed in position by
stiff muscles. Treatment with BOTOX is not meant to replace your existing
physical therapy or other rehabilitation that your doctor may have prescribed. 

It is not known whether BOTOXand BOTOX Cosmetic are safe or effective for severe
sweating anywhere other than your armpits. 

IMPORTANT SAFETY INFORMATION
BOTOX and BOTOX Cosmeticmay cause serious side effects that can be life
threatening. Call your doctor or get medical help right away if you have any of
these problems any time (hours to weeks) after injection of BOTOX or BOTOX
Cosmetic:

* Problems swallowing, speaking, or breathing, due to weakening ofassociated
muscles, can be severe and result in loss of life. You are at the highest risk
if these problems are pre-existing before injection. Swallowing problems may
last for several months 
* Spread of toxin effects. The effect of botulinum toxin may affect areas away
from the injection site and cause serious symptoms including: loss of strength
and all-over muscle weakness, double vision, blurred vision and drooping
eyelids, hoarseness or change or loss of voice (dysphonia), trouble saying words
clearly (dysarthria), loss of bladder control, trouble breathing, trouble
swallowing. If this happens, do not drive a car, operate machinery, or do other
dangerous activities

There has not been a confirmed serious case of spread of toxin effect away from
the injection site when BOTOX has been used at the recommended dose to treat
chronic migraine, severe underarm sweating, blepharospasm, strabismus, or when
BOTOX Cosmetic has been used at the recommended dose to treat frown lines. 

Do not take BOTOX or BOTOX Cosmetic if you: are allergic to any of the
ingredients in BOTOX (see Medication Guide for ingredients); had an allergic
reaction to any other botulinum toxin product such as Myobloc
(rimabotulinumtoxinB), Dysport(abobotulinumtoxinA), or
Xeomin(incobotulinumtoxinA); have a skin infection at the planned injection
site. 

Do not take BOTOX for the treatment of urinary incontinence if you: have a
urinary tract infection (UTI) or cannot empty your bladder on your own and are
not routinely catheterizing. 

Due to the risk of urinary retention (not being able to empty the bladder), only
patients who are willing and able to initiate catheterization post-treatment, if
required, should be considered for treatment. 

Patients treated for overactive bladder
In clinical trials, 6.5% of patients (36/552) initiated clean intermittent
catheterization for urinary retention following treatment with BOTOX 100 Units
as compared to 0.4% of patients (2/542) treated with placebo. The median
duration of catheterization for these patients treated with BOTOX 100 Units was
63 days (minimum 1 day to maximum 214 days) as compared to a median duration 11
days (minimum 3 days to maximum 18 days) for patients receiving placebo. 

Patients with diabetes mellitus treated with BOTOX were more likely to develop
urinary retention than non-diabetics. 

Patients treated for overactive bladder due to neurologic disease
In clinical trials, 30.6% of patients (33/108) who were not using clean
intermittent catheterization (CIC) prior to injection, required catheterization
for urinary retention following treatment with BOTOX 200 Units as compared to
6.7% of patients (7/104) treated with placebo. The median duration of
post-injection catheterization for these patients treated with BOTOX 200 Units
(n=33) was 289 days (minimum 1 day to maximum 530 days) as compared to a median
duration 358 days (minimum 2 days to maximum 379 days) for patients receiving
placebo (n=7). 

Among patients not using CIC at baseline, those with MS were more likely to
require CIC post-injection than those with SCI. 

The dose of BOTOX and BOTOX Cosmetic is not the same as, or comparable to,
another botulinum toxin product.

Serious and/or immediate allergic reactions have been reported. These reactions
include itching, rash, red itchy welts, wheezing, asthma symptoms, or dizziness
or feeling faint. Tell your doctor or get medical help right away if you
experience any such symptoms; further injection of BOTOX or BOTOX Cosmeticshould
be discontinued. 

Tell your doctor about all your muscle or nerve conditions suchas amyotrophic
lateral sclerosis (ALS or LouGehrig`s disease), myasthenia gravis, or
Lambert-Eatonsyndrome, as you may be at increased risk of serious side effects
including severe dysphagia (difficulty swallowing) and respiratory compromise
(difficulty breathing) from typical doses of BOTOX or BOTOX Cosmetic. 

Tell your doctor if you have any breathing-related problems. Your doctor will
want to monitor you for any breathing problems during your treatment with BOTOX
for upper limb spasticity or for detrusor overactivity associated with a
neurologic condition. The risk of pulmonary effects in patients with compromised
respiratory status is increased in patients receiving BOTOX. 

Cornea problems have been reported. Cornea (surface of the eye) problems have
been reported in some people receiving BOTOX for their blepharospasm, especially
in people with certain nerve disorders. BOTOX may cause the eyelids to blink
less, which could lead to the surface of the eye being exposed to air more than
is usual. Tell your doctor if you experience any problems with your eyes while
receiving BOTOX. Your doctor may treat your eyes with drops, ointments, contact
lenses, or with an eye patch. 

Bleeding behind the eye has been reported. Bleeding behind the eyeball has been
reported in some people receiving BOTOX for their strabismus. Tell your doctor
if you notice any new visual problems while receiving BOTOX. 

Bronchitis and upper respiratory tract infections (common colds) have been
reported. Bronchitis was reported more frequently in people receiving BOTOX for
their upper limb spasticity. Upper respiratory infections (common colds) were
also reported more frequently in people with prior breathing-related problems. 

Autonomic Dysreflexia in Patients Treated for Detrusor Overactivity Associated
With a Neurologic Condition
Autonomic dysreflexia associated with intradetrusor injections of BOTOX could
occur in patients treated for detrusor overactivity associated with a neurologic
condition and may require prompt medical therapy. In clinical trials, the
incidence of autonomic dysreflexia was greater in patients treated with BOTOX
200 Units compared with placebo (1.5% versus 0.4%, respectively). 

Human albumin and spread of viral diseases. BOTOX and BOTOX Cosmetic contains
albumin, a protein component of human blood. The potential risk of spreading
viral diseases (eg, Creutzfeldt-Jakob disease [CJD]) via human serum albumin is
extremely rare. No cases of viral diseases or CJD have ever been reported in
association with human serum albumin. 

Tell your doctor about all your medical conditions, including if you: have or
have had bleeding problems; have plans to have surgery; had surgery on your
face; weakness of forehead muscles, such as trouble raising your eyebrows;
drooping eyelids; any other abnormal facial change; have symptoms of a urinary
tract infection (UTI) and are being treated for urinary incontinence. Symptoms
of a urinary tract infection may include pain or burning with urination,
frequent urination, or fever; have problems emptying your bladder on your own
and are being treated for urinary incontinence; are pregnant or plan to become
pregnant (it is not known if BOTOX or BOTOX Cosmetic can harm your unborn baby);
are breastfeeding or plan to breastfeed (it is not known if BOTOX or BOTOX
Cosmetic passes into breast milk). 

Tell your doctor about all the medicines you take, including prescription and
nonprescriptionmedicines, vitamins, and herbal products. Using BOTOX or BOTOX
Cosmetic with certain other medicines may cause serious side effects. Do not
start any new medicines until you have told your doctor that you have received
BOTOX or BOTOX Cosmetic in the past.

Especially tell your doctor if you: have received any other botulinum toxin
product in the last 4 months; have received injections of botulinum toxin such
as Myobloc, Dysport, or Xeominin the past (be sure your doctor knows exactly
which product you received); have recently received an antibiotic by injection;
take muscle relaxants; take an allergy or cold medicine; take a sleep medicine;
take anti-platelets (aspirin-like products) or anti-coagulants (blood thinners).


Other side effects of BOTOX andBOTOX Cosmetic include: dry mouth, discomfort or
painat the injection site, tiredness, headache, neck pain,and eye problems:
double vision, blurred vision,decreased eyesight, drooping eyelids, swelling
ofyour eyelids, and dry eyes. In people being treated for urinary incontinence,
other side effects include: urinary tract infection, painful urination, and/or
inability to empty your bladder on your own. If you have difficulty fully
emptying your bladder after receiving BOTOX, you may need to use disposable
self-catheters to empty your bladder up to a few times each day until your
bladder is able to start emptying again. 

For more information refer to the Medication Guide or talk with your doctor. 

You are encouraged to report negative side effects of prescription drugs to the
FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. 

Please see BOTOX full Product Information including Boxed Warning and Medication
Guide.

Please see BOTOX Cosmetic full Product Information including Boxed Warning and
Medication Guide.

About Allergan, Inc.
Allergan is a multi-specialty health care company established more than 60 years
ago with a commitment to uncover the best of science and develop and deliver
innovative and meaningful treatments to help people reach their life`s
potential. Today, we have approximately 10,500 highly dedicated and talented
employees, global marketing and sales capabilities with a presence in more than
100 countries, a rich and ever-evolving portfolio of pharmaceuticals, biologics,
medical devices and over-the-counter consumer products, and state-of-the-art
resources in R&D, manufacturing and safety surveillance that help millions of
patients see more clearly, move more freely and express themselves more fully.
From our beginnings as an eye care company to our focus today on several medical
specialties, including eye care, neurosciences, medical aesthetics, medical
dermatology, breast aesthetics, obesity intervention and urologics, Allergan is
proud to celebrate more than 60 years of medical advances and proud to support
the patients and physicians who rely on our products and the employees and
communities in which we live and work. For more information regarding Allergan,
go to: www.allergan.com. 

Forward-Looking Statements
This press release contains "forward-looking statements," including the
statements by Dr. Whitcup, Dr. Nitti and other statements regarding research and
development and regulatory outcomes, efficacy, adverse reactions, market and
product potential, product availability and other statements regarding BOTOX®.
These statements are based on current expectations of future events. If
underlying assumptions prove inaccurate or unknown risks or uncertainties
materialize, actual results could vary materially from Allergan's expectations
and projections. Risks and uncertainties include, among other things, general
industry, biologic and pharmaceutical market conditions; technological advances
and patents attained by competitors; challenges inherent in the research and
development and regulatory processes; challenges related to new product
marketing, such as the unpredictability of market acceptance for new
pharmaceutical and biologics products and/or the acceptance of new indications
for such products; inconsistency of treatment results among patients; potential
difficulties in manufacturing a new product; and governmental laws and
regulations affecting domestic and foreign operations. Allergan expressly
disclaims any intent or obligation to update these forward-looking statements
except as required by law. Additional information concerning these risks and
other risk factors can be found in press releases issued by Allergan, as well as
Allergan's public filings with the Securities and Exchange Commission, including
the discussion under the heading "Risk Factors" in Allergan's most recent Form
10-K and any subsequent Quarterly Reports on Form 10-Q. 

© 2013 Allergan, Inc. Irvine, CA 92612. ® marks owned by Allergan, Inc. All
rights reserved.
Myobloc® is a registered trademark of Solstice Neurosciences, Inc.
Dysport® is a registered trademark of Ipsen Biopharm, Ltd.
Xeomin®is a registered trademark of Merz Pharma Gmbh & Co. 

*Dr. Nitti received research support for conducting BOTOX clinical trials at NYU
Langone and is a member of an advisory board for Allergan, Inc.

1 BOTOX Prescribing Information, updated January 2013
2 Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of
overactive bladder in the United States. World J Urol 2003:20:327-336; based on
2010 U.S. Census data and U.S. adult population [as of Jan. 10, 2013]
3 National Patient Count, IMS Total Patient Tracker, USC 24100, MAT 11/12
4 D`Souza et al. Persistence, Adherence, and Switch Rates Among Extended-Release
and Immediate-Release Overactive Bladder Medications in a Regional Managed Care
Plan. J. Managed Care Pharm. 2008;14(3):291-301
5 Allergan data on file
6 Allergan data on file; Global Medical Affairs
7 Allergan data on file; Global Safety and Epidemiology
8 Allergan data on file; Global Literature & Information Services and Global
Regulatory Affairs

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Allergan Contacts
Bonnie Jacobs (856) 912-9965 (media), jacobs_bonnie@allergan.com
Heather Katt (714) 697-2981 (media), katt_heather@allergan.com
Jim Hindman (714) 246-4636 (investors)
Joann Bradley (714) 246-4766 (investors)
David Nakasone (714) 246-4474 (investors) 

Copyright Business Wire 2013

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