SHIRE PLC - Shire Announces FDA Approval of Once-Daily INTUNIV(TM)

Shire Announces FDA Approval of Once-Daily INTUNIV(TM) (guanfacine) Extended
Release Tablets for the Treatment of ADHD in Children and Adolescents Aged 6 to
17



INTUNIV, the first nonscheduled alpha-2A receptor agonist indicated for ADHD,
demonstrated improvement in a range of ADHD symptoms that can be disruptive,
such as inattention, arguing with adults, hyperactivity, impulsivity, and
losing one's temper.

September 03, 2009 - Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty
biopharmaceutical company, today announced that it has received approval from
the US Food and Drug Administration (FDA) for INTUNIV(TM) (guanfacine) Extended
Release Tablets for the treatment of Attention-Deficit/Hyperactivity Disorder (
ADHD) in children and adolescents aged 6 to 17 years. INTUNIV, a once-daily
formulation of guanfacine, is the first selective alpha-2A adrenergic receptor
agonist approved for the treatment of ADHD. Although the mechanism of action is
unknown, INTUNIV is thought to directly engage receptors found in the
prefrontal cortex - an area of the brain that has been linked in preclinical
research to ADHD. Stimulation of the postsynaptic alpha-2A receptors is thought
to strengthen working memory, reduce susceptibility to distraction, improve
attention regulation, improve behavioral inhibition, and enhance impulse
control.

"Shire is proud to introduce INTUNIV, providing clinicians, patients, and their
families with a novel ADHD treatment option," said Mike Cola, President of
Shire Specialty Pharmaceuticals. "This is a complex disorder in which patients
may present with multiple symptoms and behaviors that can be disruptive.
INTUNIV expands the Shire ADHD portfolio with a nonscheduled medication,
allowing clinicians to optimize their overall approach toward managing ADHD and
may help provide symptom control for children and teens with ADHD who often
have difficulty responding appropriately to everyday situations and
challenges."

Once-daily INTUNIV is expected to be available in US pharmacies in November and
will come in four dosage strengths (1 mg, 2 mg, 3 mg, and 4 mg). INTUNIV will
be marketed in the United States by the existing Shire ADHD sales team of
nearly 600 representatives. INTUNIV is not a controlled substance and has no
known potential for abuse or dependence.

"Everyday situations and challenges may be difficult for children and
adolescents with ADHD as it is a disruptive disorder that includes symptoms and
behaviors such as being easily distracted, always on the go, interrupting
others, arguing with adults, or temper outbursts," said Frank A. Lopez, MD, a
neurodevelopmental pediatrician in private practice at Children's Developmental
Center in Winter Park, Florida. "In clinical trials, INTUNIV, a selective
alpha-2A receptor agonist, significantly reduced ADHD symptoms across a full
day as measured by parents at 6 pm, 8 pm, and 6 am the next morning. This is
important because children with ADHD require symptom control at home, school,
and during after school activities."

The introduction of INTUNIV is consistent with the strategy of Shire to expand
and diversify its ADHD portfolio, which now consists of four ADHD treatment
options of scheduled and nonscheduled medicines in the United States and two
ADHD medicines available outside the United States.

Additional information about INTUNIV and Full Prescribing Information are
available at http://www.intuniv.com.

INTUNIV Demonstrated Significant Reduction in ADHD Symptoms

The efficacy of INTUNIV in the treatment of ADHD was established in two,
similarly designed, placebo-controlled clinical trials in children and
adolescents aged 6 to 17 years who met Diagnostic and Statistical Manual of
Mental Disorders-IV (DSM-IV(R)) criteria for ADHD. Statistically significant
improvements were reported by investigators, parents, and teachers.

The first pivotal trial was a phase III, double-blind, parallel-group trial, in
which investigators randomized 345 children aged 6 to 17 years to either a
placebo or a fixed 2-mg, 3-mg, or 4-mg dose of INTUNIV given once daily during
an eight-week period. The second pivotal trial was a phase III, double-blind,
parallel-group trial, in which investigators randomized 324 children aged 6 to
17 years to either a placebo or a fixed 1-mg, 2-mg, 3-mg, or 4-mg dose of
INTUNIV given once daily during a nine-week period, with the 1 mg assigned only
to patients weighing less than 50 kg (110 lbs).

In both trials, doses were increased in increments of 1 mg per week, and
investigators evaluated participants' signs and symptoms of ADHD on a
once-weekly basis using the clinician administered and scored ADHD Rating
Scale-IV (ADHD-RS-IV), a scale frequently used in ADHD clinical trials that
assesses hyperactive, impulsive, and inattentive symptoms. The primary outcome
was the change in total ADHD-RS-IV scores from baseline to end point in both
studies.

Both trials demonstrated statistically significant improvements in ADHD-RS-IV
scores in patients taking INTUNIV beginning one to two weeks after patients
began receiving once-daily doses of INTUNIV. In the first pivotal trial, the
mean reduction in ADHD-RS-IV total scores at end point were -16.7 for INTUNIV
compared to -8.9 for placebo (P<.0001), the mean reduction in ADHD-RS-IV total
scores in the second pivotal trial were -19.6 for INTUNIV and -12.2 for placebo
(P=.0040). Placebo-adjusted LS mean changes from baseline were statistically
significant for all INTUNIV doses in the randomized treatment groups in both
studies.

Additional secondary efficacy outcome measures included the Conners' Parent
Rating Scale-Revised: Short Form (CPRS-R) and the Conners' Teacher Rating
Scale-Revised: Short Form (CTRS-R). CPRS-R and CTRS-R are comprehensive scales
that use parent and teacher observer and self-report ratings to help assess
ADHD and evaluate behavioral issues in children and adolescents. Among some of
the symptoms measured were: inattentiveness/being easily distracted, running
around or climbing excessively, arguing with adults, losing temper, and
interrupting or intruding on others. Significant improvements were seen on both
scales: based on the CPRS-R, parents reported significant improvement across a
full day (as measured at 6 pm, 8 pm, and 6 am the next morning); based on the
CTRS-R, which was used only in the first pivotal trial, teachers reported
significant improvement throughout the school day (as measured at 10 am and 2
pm).

Investigators also measured the efficacy of INTUNIV with the Clinical Global
Impressions-Improvement (CGI-I) scale, a standard assessment used to rate the
improvement of a patient's illness over the course of the study. The first
pivotal trial found the percentage of subjects taking INTUNIV who were rated
"much improved" or "very much improved" at end point ranged from approximately
50 to 56 percent across all doses versus approximately 26 percent for placebo
(P<.05). Subjects taking INTUNIV in the second pivotal trial who rated "much
improved" or "very much improved" at end point ranged from 54 to 56 percent
across 1-mg (P=.0070), 3-mg (P=.0060), and 4-mg (P=.0040) doses versus 30
percent for placebo; the placebo-INTUNIV difference for the 2-mg dose was not
significant (P=.1404).

Safety was also evaluated during these pivotal trials and safety data showed
that adverse events reported by participants using INTUNIV were generally mild
to moderate in severity, with the most common side effects being sedative in
nature. Sedation-related, treatment-emergent adverse events were among the most
common and were usually transient and mild to moderate in severity.
Treatment-related adverse events greater than 10 percent included somnolence
(32 percent), headache (26 percent), fatigue (18 percent), upper abdominal pain
(14 percent), and sedation (13 percent). Small to modest changes in blood
pressure, pulse rate, and ECG parameters were observed.

Important Safety Information

INTUNIV is indicated for the treatment of Attention Deficit Hyperactivity
Disorder (ADHD) in children and adolescents aged 6 to 17. Efficacy was
established in two controlled clinical trials (8 and 9 weeks in duration). The
physician electing to use INTUNIV for extended periods should periodically
reevaluate its long-term usefulness for the individual patient.

INTUNIV should not be used in patients with a history of hypersensitivity to
guanfacine or any of its inactive ingredients or by patients taking other
products containing guanfacine

Hypotension, bradycardia, and syncope were observed in clinical trials. Use
INTUNIV with caution in treating patients who have experienced hypotension,
bradycardia, heart block, or syncope, or who may have a condition that
predisposes them to syncope; are treated concomitantly with antihypertensives
or other drugs that can reduce blood pressure or heart rate or increase the
risk of syncope. Heart rate and blood pressure should be measured prior to
initiation of therapy, following dose increases, and periodically while on
therapy. Patients should be advised to avoid becoming dehydrated or overheated.

Sedation and somnolence were commonly observed in clinical trials. The
potential for additive sedative effects with CNS depressant drugs should be
considered. Patients should be cautioned against operating heavy equipment or
driving until they know how they respond to INTUNIV.

Common adverse reactions in patients taking INTUNIV that may be dose-related
over the range of 1 to 4 mg/day include somnolence, sedation, abdominal pain,
dizziness, hypotension/decreased blood pressure, dry mouth, and constipation.

About ADHD
ADHD is one of the most common psychiatric disorders in children and
adolescents.  Worldwide prevalence of ADHD is estimated at 5.3 percent (with
large variability), according to a comprehensive systematic review of this
topic published in 2007 in the American Journal of Psychiatry.  In the United
States, approximately 7.8 percent of all school-aged children, or about 4.4
million children aged 4 to 17 years, have been diagnosed with ADHD at some
point in their lives, according to the Centers for Disease Control and
Prevention (CDC).  The disorder is also estimated to affect 4.4 percent of US
adults aged 18 to 44 based on results from the National Comorbidity Survey
Replication. When this percentage is extrapolated to the full US population
aged 18 and over, approximately 9.8 million adults are believed to have ADHD.



ADHD is a psychiatric behavioral disorder that manifests as a persistent
pattern of inattention and/or hyperactivity-impulsivity that is more frequent
and severe than is typically observed in individuals at a comparable level of
development. The specific etiology of ADHD is unknown and there is no single
diagnostic test for this syndrome.  Adequate diagnosis requires the use of
medical and special psychological, educational, and social resources, utilizing
diagnostic criteria such as Diagnostic and Statistical Manual of Mental
Disorders-IV (DSM-IV(R)) or International Classification of Diseases 10 (ICD-10).

Although there is no cure for ADHD, there are accepted treatments that
specifically target its symptoms. Standard treatments include educational
approaches, psychological or behavioral modification, and medication.

For further information please contact:

Investor Relations  Clea Rosenfeld (Rest of the World)       +44 1256 894 160

                    Eric Rojas (North America)               +1 617 551 9715

Media               Jessica Mann (Rest of the World)         +44 1256 894 280

                    Matthew Cabrey (North America)           +1 484 595 8248

                    Debra Gemme (Porter Novelli for Shire)   +1 212 601 8342

Notes to editors

SHIRE PLC

Shire's strategic goal is to become the leading specialty biopharmaceutical
company that focuses on meeting the needs of the specialist physician. Shire
focuses its business on attention deficit hyperactivity disorder (ADHD), human
genetic therapies (HGT) and gastrointestinal (GI) diseases as well as
opportunities in other therapeutic areas to the extent they arise through
acquisitions. Shire's in-licensing, merger and acquisition efforts are focused
on products in specialist markets with strong intellectual property protection
and global rights. Shire believes that a carefully selected and balanced
portfolio of products with strategically aligned and relatively small-scale
sales forces will deliver strong results.

For further information on Shire, please visit the Company's website:
www.shire.com.

"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF
1995

Statements included herein that are not historical facts are forward-looking
statements. Such forward-looking statements involve a number of risks and
uncertainties and are subject to change at any time. In the event such risks or
uncertainties materialize, the Company's results could be materially adversely
affected. The risks and uncertainties include, but are not limited to, risks
associated with: the inherent uncertainty of research, development, approval,
reimbursement, manufacturing and commercialization of the Company's Specialty
Pharmaceutical and Human Genetic Therapies products, as well as the ability to
secure and integrate new products for commercialization and/or development;
government regulation of the Company's products; the Company's ability to
manufacture its products in sufficient quantities to meet demand; the impact of
competitive therapies on the Company's products; the Company's ability to
register, maintain and enforce patents and other intellectual property rights
relating to its products; the Company's ability to obtain and maintain
government and other third-party reimbursement for its products; and other
risks and uncertainties detailed from time to time in the Company's filings
with the Securities and Exchange Commission.

                                     # # #



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Press Release

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