Shire Announces Study Results of the Effects of INTUNIV(TM) (Guanfacine) Extended...

Shire Announces Study Results of the Effects of INTUNIV(TM) (Guanfacine)
Extended Release on Secondary Measures in Children with ADHD and Oppositional
Symptoms

SAN FRANCISCO, May 18 /PRNewswire-FirstCall/ -- Shire plc (LSE: SHP, Nasdaq:
SHPGY), the global specialty biopharmaceutical company, today announced new
findings on INTUNIV (guanfacine) extended release, a selective
alpha-2A-agonist, at a major psychiatric meeting. This randomized placebo
controlled trial met its primary objective, which was to evaluate the effects
of INTUNIV on oppositional symptoms in children aged 6 to 12 years with a
diagnosis of ADHD and the presence of oppositional symptoms. The data
presented today on this investigational compound reviewed secondary efficacy
measures from three different rating scales.

"A significant number of pediatric ADHD patients present with behaviors such
as anger, resentfulness, defiance, and arguing with adults. It can be
complicated for physicians and caregivers to find the right medication to
control symptoms for children with ADHD exhibiting these behaviors," said
Daniel Connor, MD, professor and division chief of child and adolescent
psychiatry at the University of Connecticut Medical School. "When considered
with the primary efficacy results of the current study, these data provide
additional support for the clinical efficacy of INTUNIV for treating ADHD in
this patient population."

On January 26, 2009, Shire filed a resubmission to the US Food and Drug
Administration (FDA) of the New Drug Application to support approval for the
treatment of ADHD in children and adolescents. Once available, INTUNIV will
be the first selective alpha-2A receptor agonist approved for the treatment of
ADHD.

INTUNIV Demonstrated Significant Efficacy in Secondary Endpoints
In this randomized, placebo-controlled, flexible-dose study, INTUNIV
demonstrated significant ADHD symptom improvement in patients with
oppositional symptoms as measured by the ADHD Rating Scale-IV (ADHD-RS-IV), a
scale frequently used in ADHD clinical trials. In results from this study
presented today, INTUNIV also demonstrated symptom improvement as measured by
three different rating scales: the Clinical Global Impressions-Improvement
(CGI-I), the Conduct Problem Subscale of the New York Parent Rating
Scale-School-Aged (NYPRS-S), and the Parent Stress Index-Short Form (PSI/SF)
questionnaire.

When using the CGI-I scale, investigators rated 7 out of 10 patients as "very
much improved" or "much improved" compared with placebo (71.5 percent vs 32.0
percent; P<.001). The CGI-I scale is a standard assessment used to rate the
severity of a patient's illness and improvement over the course of the study.

Significantly greater symptom reductions were also seen on the Conduct Problem
Subscale of the NYPRS-S in the INTUNIV group compared to placebo (-16.0 vs
-9.6; P<.001). In this parent-rated scale, numerous symptoms including anger,
defiance, arguing with adults, and loss of temper were assessed in children on
a four-point scale and a higher score indicated greater problems. Additional
improvement was demonstrated on the PSI/SF, a parent rated 36-item
questionnaire that measured stressful areas in parent-child interactions. On
the PSI/SF scale, the INTUNIV group reduced its score by 17.0 compared to 7.7
for the placebo group (P=.002).

"These data are testament to Shire's commitment to furthering ADHD research,
and finding new treatment options for the multiple symptoms of ADHD, many of
which are very disruptive at home and at school," said Michael Yasick, Senior
Vice President of Shire's ADHD Business Unit.

In this study, the most commonly reported treatment emergent adverse events
(greater than or equal to 10 percent) were somnolence, headache, sedation,
upper abdominal pain, fatigue and irritability. The majority of treatment
emergent adverse events were mild to moderate in severity. There were no
serious adverse events.

About INTUNIV
INTUNIV is currently being studied as a once-daily, extended release
formulation of guanfacine designed to provide steady delivery of drug
throughout the day. INTUNIV is pending FDA approval for the treatment of ADHD
in children and adolescents. In clinical trials, INTUNIV demonstrated
significant reduction in ADHD symptoms. INTUNIV is not a controlled substance
and has no known mechanism for abuse or dependence.

Guanfacine, the active ingredient in INTUNIV, is thought to work directly by
binding selectively to alpha-2A adrenergic receptors located in the prefrontal
cortex. The prefrontal cortex is an area of the brain associated with working
memory, behavioral inhibition, regulation of attention, distractibility, and
impulsivity. Although the mechanism of action of guanfacine in the treatment
of ADHD is not fully understood, preclinical research suggests this selective
alpha-2A agonist strengthens working memory and prefrontal cortex neuronal
firing. This research supports the use of guanfacine for the treatment of
ADHD.

In pivotal clinical trials, 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 or 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). Syncope occurred in approximately 1 percent of pediatric
patients in the clinical program. The majority of these cases occurred in the
long-term, open label studies. Small to modest changes in blood pressure,
pulse rate, and ECG parameters were observed.

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 US 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).

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(TM)-IV (DSM-IV) 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.

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.

THE "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.

SOURCE Shire plc

Debra Gemme, +1-212-601-8342, +1-703-298-4030 (mobile),
debra.gemme@porternovelli.com; or Alana Brier, +1-212-601-8432,
+1-203-565-3980 (mobile), alana.brier@porternovelli.com, both of Porter
Novelli for Shire