FDA Approves Labeling Change for VYVANSE(R) (lisdexamfetamine dimesylate) CII to...

FDA Approves Labeling Change for VYVANSE(R) (lisdexamfetamine dimesylate) CII
to Include Supplementary Clinical Data Supporting Efficacy at 13 Hours
Postdose in Children Aged 6 to 12 with ADHD

ADHD symptom control demonstrated from the first time point measured (1.5
hours) through 13 hours postdose

PHILADELPHIA, June 1 /PRNewswire-FirstCall/ -- Shire plc (LSE: SHP, Nasdaq:
SHPGY), the global specialty biopharmaceutical company, today announced that
the US Food and Drug Administration (FDA) has approved a change to the
prescribing information for its once-daily Attention Deficit Hyperactivity
Disorder (ADHD) treatment VYVANSE(R) (lisdexamfetamine dimesylate) CII, to
include supplemental data that demonstrated significant ADHD symptom control
in children aged 6 to 12 from the first time point measured (1.5 hours)
through 13 hours postdose. VYVANSE is now the first and only oral ADHD
stimulant treatment to have 13-hour postdose efficacy data for pediatric
patients included in its product labeling.

"Children with ADHD who still exhibit symptoms into the evening might need a
treatment that provides a long duration of effect from morning, through
homework and family time," said Michael Yasick, Senior Vice President of the
ADHD Business Unit at Shire. "The FDA approval of this labeling change for
VYVANSE provides important additional information for physicians on the
duration of effect of VYVANSE and use as a once daily treatment option."

This update to the VYVANSE product labeling is based on a 13-hour analog
classroom study that demonstrated improvements in behavior, inattention, and
math test scores in children aged 6 to 12 from the first time point measured
(1.5 hours) through the last time point assessed (13 hours) postdose. This
study supports the results of a previous Phase 2 laboratory school study in
which VYVANSE demonstrated ADHD symptom control from the first time point
assessed (two hours postdose) with duration of efficacy up to 12 hours
postdose. The adverse events in the 12-hour study for patients taking VYVANSE
during the double-blind treatment period, which were greater than or equal to
2 percent, were insomnia, decreased appetite, and anorexia.

VYVANSE Demonstrated Significant Efficacy Versus Placebo at 13 Hours Postdose
The study that led to this approval of revised labeling for VYVANSE was a
randomized, double-blind, placebo-controlled, analog classroom study that
assessed the efficacy and safety of VYVANSE in 129 children aged 6 to 12 years
with ADHD. Following a four-week, open-label, dose-optimization phase with
VYVANSE at 30 mg, 50 mg, and 70 mg doses, patients entered a two-week,
double-blind, crossover phase where they were randomized into two groups. One
group received their optimal dose of VYVANSE the first week and placebo the
second week. The second group received placebo the first week and their
optimal dose of VYVANSE the second week.

The primary objective of this study was to assess the time of onset of VYVANSE
compared with placebo, as measured by the Swanson, Kotkin, Agler, M-Flynn, and
Pelham Deportment (SKAMP-D) rating scale. Secondary objectives included
assessment of the duration of efficacy of VYVANSE compared with placebo, as
measured by the SKAMP-D scale, and assessment of efficacy and time of onset of
VYVANSE compared with placebo as measured by SKAMP Attention (SKAMP-A), and
Permanent Product Measure of Performance (PERMP) scales.

In the study, VYVANSE demonstrated significant efficacy versus placebo at 1.5
hours, the first time point measured. Further, VYVANSE treatment was
associated with significant efficacy as measured by both subjective (SKAMP-D
and SKAMP-A) and objective (PERMP) assessments from the first time point (1.5
hours) through the last time point (13 hours) assessed during the classroom
day, and at all time points in between (2.5, 5.0, 7.5, 10.0 and 12.0 hours).

Safety was also evaluated during the study. The most frequently reported
adverse events (greater than or equal to 10 percent and twice placebo) in the
dose optimization phase for patients taking VYVANSE were decreased appetite,
insomnia, headache, irritability, upper abdominal pain, and affect lability
(mood swings).

VYVANSE, which was introduced in the United States in July 2007 for the
treatment of ADHD in children aged 6 to 12 years and approved in April 2008 to
treat ADHD in adults, is currently available in six dosage strengths of 20 mg,
30 mg, 40 mg, 50 mg, 60 mg, and 70 mg. To date, more than 5 million VYVANSE
prescriptions have been filled, bringing the current market share to 12
percent based on weekly branded prescription volume. Additionally, VYVANSE
formulary coverage has been positive, with 10 of 11 top managed care plans
covering the product in a preferred formulary position.

VYVANSE is a therapeutically inactive prodrug, in which d-amphetamine is
covalently bonded to l-lysine, and after oral ingestion it is converted to
pharmacologically active d-amphetamine. The conversion of VYVANSE to
d-amphetamine is not affected by gastrointestinal pH and is unlikely to be
affected by alterations in GI transit times.

Additional information about VYVANSE and Full Prescribing Information,
including Medication Guide, are available at www.vyvanse.com.

About VYVANSE
Vyvanse is indicated for the treatment of ADHD. Efficacy based on two
controlled trials in children aged 6 to 12 and one controlled trial in adults.

Tell the doctor about any heart conditions, including structural
abnormalities, that you, your child, or a family member, may have. Inform
the doctor immediately if you or your child develops symptoms that suggest
heart problems, such as chest pain or fainting.

Vyvanse should not be taken if you or your child has advanced disease of the
blood vessels (arteriosclerosis); symptomatic heart disease; moderate to
severe high blood pressure; overactive thyroid gland (hyperthyroidism); known
allergy or unusual reactions to drugs called sympathomimetic amines (for
example, pseudoephedrine); seizures; glaucoma; a history of problems with
alcohol or drugs; agitated states; taken a monoamine oxidase inhibitor (MAOI)
within the last 14 days.

Tell the doctor before taking Vyvanse if you or your child is being treated
for or has symptoms of depression (sadness, worthlessness, or hopelessness) or
bipolar disorder; has abnormal thought or visions, hears abnormal sounds, or
has been diagnosed with psychosis; has had seizures or abnormal EEGs; has or
has had high blood pressure; exhibits aggressive behavior or hostility. Tell
the doctor immediately if you or your child develops any of these conditions
or symptoms while taking Vyvanse.

Abuse of amphetamines may lead to dependence. Misuse of amphetamine may cause
sudden death and serious cardiovascular adverse events. These events have
also been reported rarely with amphetamine use.

Talk to your health care provider if your child experiences slowing of growth
(height and weight). Children should have their height and weight checked
periodically while taking Vyvanse. Your healthcare provider may stop Vyvanse
treatment if a problem is found during these check-ups.

Vyvanse was generally well tolerated in clinical studies. The most common
side effects reported in studies of Vyvanse were: children - decreased
appetite, difficulty falling asleep, stomachache, and irritability; adult -
decreased appetite, difficulty falling asleep, and dry mouth.

Aggression, new abnormal thoughts/behaviors, mania, growth suppression,
worsening of motion or verbal tics, and Tourette's syndrome have been
associated with use of drugs of this type. Tell the doctor if you or your
child has blurred vision while taking Vyvanse.

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-TR) 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

Investor Relations: Clea Rosenfeld (Shire Rest of the World) +44 1256 894 160
or Eric Rojas (Shire North America) +1-617-551-9715; or Media: Matthew Cabrey
(Shire North America) +1-484-595-8248, or Mindy Huber (Porter Novelli for
Shire) +1-212-601-8330