Positive Response from European Regulatory Procedure Supports Approval of Elvanse® (lisdexamfetamine dimesylate) for ADHD

Nyon, Switzerland (ots/PRNewswire) -

Shire plc today announces a positive outcome from the European
Decentralised Procedure (DCP) for Elvanse(R) (to be known as
Tyvense(R) in Ireland). Elvanse is indicated as part of a
comprehensive treatment programme for attention deficit/hyperactivity
disorder (ADHD) in children aged 6 years of age and over when
response to previous methylphenidate treatment is considered
clinically inadequate.[1]

The UK Medicines and Healthcare products Regulatory Agency (MHRA)
acted as the Reference Member State on behalf of seven other European
countries participating in the procedure (Denmark, Finland, Germany,
Ireland, Norway, Spain and Sweden). Product labelling has been agreed
by these countries, which will now issue their national Marketing
Authorisations (approvals); this typically takes a further one to
three months. In some countries, negotiations with national pricing
and reimbursement authorities will now be required before the
medicine is made available to patients, and the timing for this
process varies between countries.

Elvanse was accepted for review by the MHRA in January 2012, with
the application based on two European Phase 3 studies in children and
adolescents with ADHD and further supported by clinical data from the
USA.[2],[3]

Elvanse is a long-acting, once daily medication for the control of
the symptoms of ADHD.[2],[3] Elvanse is the first of a new class of
dopamine modulators approved in Europe that uses pro-drug technology
to release the active drug in the body. It is currently available in
the USA and Canada under the trade name Vyvanse(R), for the treatment
of ADHD in children, adolescents and adults, and in Brazil under the
trade name Venvanse(R), for the treatment of ADHD in children aged 6
to 12 years. It is currently the most prescribed branded ADHD
medicine in the USA. The efficacy and safety of Elvanse has been
studied in many clinical trials and Elvanse has been prescribed to
treat more than 4 million patients in the USA, Brazil and Canada.[4]

"We are delighted that the national approvals of Elvanse in Europe
are now imminent," said Angus Russell, CEO, Shire. "ADHD is one of
the most common psychiatric disorders affecting children and
adolescents. As all ADHD patients are different and will vary in
their responses to the available treatments, we believe introducing
Elvanse will provide physicians with a broader range of options to
help patients with ADHD manage their individual needs effectively. We
will now work closely with the pricing and reimbursement authorities
in the respective countries to ensure that Elvanse is made available
to patients as soon as possible."

About Elvanse

Elvanse (lisdexamfetamine dimesylate) has not yet received
national marketing authorisation in each respective EU country
involved in the DCP, and national licenses are expected to be issued
one to three months after DCP closure. It is already available in the
USA and Canada (brand name Vyvanse) and in Brazil (brand name
Venvanse), where it has been used to treat over 4 million
patients.[4] Elvanse's efficacy and tolerability have been studied in
clinical trials both in the USA and Europe.[2],[3],[5]-[11]

Elvanse is a single daily dose prodrug medication for the
treatment of ADHD. A prodrug is a substance that is ingested in an
inactive form and then activated within the body.[12]

The inactive prodrug is absorbed from the gut into the bloodstream
where it is gradually converted to the active part of the medicine,
d-amfetamine (d-AMF).[12] The active part of Elvanse is thought to
work by increasing the levels of neurotransmitters (chemicals that
are stored in nerve cells in the brain and nervous system, which
transmit messages between the nerve cells) responsible for activity,
attention and concentration.[ 13]

Elvanse was developed with the goal of providing a long duration
of effect to help patients achieve control of their ADHD symptoms
throughout the day.[14]

Indication[1]

Elvanse is indicated as part of a comprehensive treatment
programme for attention deficit/hyperactivity disorder (ADHD) in
children aged 6 years and over when response to previous
methylphenidate treatment is considered clinically inadequate.

Treatment must be under the supervision of a specialist in
childhood and/or adolescent behavioural disorders. Diagnosis should
be made according to DSM-IV criteria or the guidelines in ICD-10 and
should be based on a complete history and evaluation of the patient.
Diagnosis cannot be made solely on the presence of one or more
symptom.

The specific aetiology of this syndrome is unknown, and there is
no single diagnostic test. Adequate diagnosis requires the use of
medical and specialised psychological, educational, and social
resources.

A comprehensive treatment programme typically includes
psychological, educational and social measures as well as
pharmacotherapy and is aimed at stabilising children with a
behavioural syndrome characterised by symptoms which may include
chronic history of short attention span, distractibility, emotional
lability, impulsivity, moderate to severe hyperactivity, minor
neurological signs and abnormal EEG. Learning may or may not be
impaired.

Elvanse is not indicated in all children with ADHD and the
decision to use the drug must be based on a very thorough assessment
of the severity and chronicity of the child's symptoms in relation to
the child's age and potential for abuse, misuse or diversion.

Appropriate educational placement is essential, and psychosocial
intervention is generally necessary. The use of Elvanse should always
be used in this way according to the licensed indication.

About Elvanse Clinical Trials

The safety and efficacy of Elvanse was studied in two European
Phase 3 studies:

Study 325:[2]A randomised, double blind, multicentre,
parallel-group, placebo- and active-controlled, dose-optimisation,
safety and efficacy study in 336 children and adolescents aged 6 to
17 years. Results of this study have been accepted for publication in
European Neuropsychopharmacology and were also presented on October
21st 2011 at the American Academy of Child and Adolescent Psychiatry
(AACAP) congress in Toronto.

Study 326:[3]A Phase 3, double blind, placebo-controlled,
randomized withdrawal, multicentre, extension, safety and efficacy
study of lisdexamfetamine dimesylate in 276 children and adolescents
aged 6-17 with attention-deficit/hyperactivity disorder. Results from
this study were presented on October 13th 2012 at the European
College of Neuropsychopharmacology (ECNP) congress in Vienna.

Misuse and abuse[1]

Stimulants including Elvanse have a potential for abuse, misuse,
dependence, or diversion for non-therapeutic uses that physicians
should consider when prescribing this product. Stimulants should be
prescribed cautiously to patients with a history of substance abuse
or dependence.

Important Safety Information[15]

- Do not take Elvanse if you or your child:
- is taking or has taken within the past 14 days an anti-depression medicine
called a monoamine oxidase inhibitor or MAOI
- is sensitive to, allergic to, or had a reaction to other stimulant
medicines
- Some people have had the following problems when taking stimulant
medicines, such as Elvanse:
- heart-related problems including:
- sudden death in people who have heart problems or heart defects
- stroke and heart attack in adults
- increased blood pressure and heart rate.
- Mental (psychiatric) problems including:

Children, Teenagers, and Adults

- new or worse behaviour and thought problems
- new or worse bipolar illness
- new or worse aggressive behaviour or hostility

Children and Teenagers

- new psychotic symptoms such as:
- hearing voices
- believing things that are not true
- being suspicious
- new manic symptoms

This is not a complete summary of safety information. For
additional safety information please see the Elvanse patient
information leaflet or discuss with your doctor. Please note that
this safety information reflects the US label which is different from
the European indication.

About ADHD

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most
common psychiatric disorders in children and
adolescents[16],[17],[18] and is recognised by the World Health
Organization (WHO).[19]

Globally, ADHD affects around 5% of children and adolescents.[20]
Based on this prevalence rate, one can estimate that 5 million young
people in the EU are suffering from ADHD.

What causes ADHD?

While the exact origin of ADHD is not known, it is thought that
the disorder may be caused by an imbalance of neurotransmitters (or
chemicals in the brain).[21]

ADHD is thought to result from complex interactions between
genetic and environmental factors,[22] with studies estimating that
genetic factors explain 60 to 75% of the aetiology of ADHD.[22],[23]

Environmental factors which may increase the risk of developing
ADHD include low birth weight/prematurity, maternal smoking during
pregnancy, and severe early psychosocial adversity (e.g. children who
have survived deprived institutional care).[22]

Notes to editors

Shire enables people with life-altering conditions to lead better
lives.

Through our deep understanding of patients' needs, we develop and
provide healthcare in the areas of:

- Behavioral Health and Gastro Intestinal conditions
- Rare Diseases
- Regenerative Medicine

as well as other symptomatic conditions treated by specialist
physicians.

We aspire to imagine and lead the future of healthcare, creating
value for patients, physicians, policymakers, payors and our
shareholders.

For further information on Shire, please visit the Company's
website: http://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 Pharmaceuticals, Human Genetic Therapies and Regenerative
Medicine products, as well as the ability to secure 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.

References

1) Elvanse European Summary of Product Characteristics
2) Coghill D, Banaschewski T, Lecendreux M et al. Efficacy And Safety Of
Lisdexamfetamine Dimesylate In Children And Adolescents With
Attention-Deficit/Hyperactivity Disorder: A Phase III, Randomized, Double-Blind,
Multicenter, Parallel-Group, Placebo- And Active Controlled, Dose-Optimized Study In
Europe. Joint Annual Meeting Of The AmericanAcademy Of Child And Adolescent Psychiatry
(AACAP) And The CanadianAcademy Of Child And Adolescent Psychiatry, 2011.
3) Coghill D, Banaschewski T, Lecendreux M et al. Maintenance Of Efficacy Of
Lisdexamfetamine Dimesylate In Children And Adolescents With Attention
Deficit/Hyperactivity Disorder: Randomized-Withdrawal Design. Paper P7. 009. Poster
presented at the 25th ECNP conference (13-17 October 2012, Vienna)
4) Shire Data on File SPD489-016
5) Biederman J et al. Efficacy and tolerability of lisdexamfetamine dimesylate
(NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III,
multicenter, randomized, double-blind, forced-dose, parallel-group study. ClinTher
2007;29:450-463.
6) Findling RL et al. Long-term effectiveness and safety of lisdexamfetamine
dimesylate in school-aged children with attention-deficit/hyperactivity disorder. CNS
Spectr 2008;13(7):614-620.
7) Findling RL et al. Effectiveness, safety, and tolerability of
lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder:
an open-label, dose-optimization study. J Child Adolesc Psychopharmacol.
2009;19(6):649-62.
8) Wigal SB et al. A 13-hour laboratory school study of lisdexamfetamine
dimesylate in school-aged children with attention-deficit/hyperactivity disorder.
Child Adolesc Psychiatry Ment Health 2009;3(1):17
9) Coghill DR, Banaschewski T, Lecendreux ML, et al. Efficacy and Safety of
Lisdexamfetamine Dimesylate in children and adolescents with ADHD: A phase 3,
randomized, double-blind, multicenter, parallel-group, placebo and active controlled,
dose-optimized study in Europe. Poster presented at the AACAP/CACAP Joint Annual
Meeting, 18-23 October 2011, Toronto, Canada.
10) Findling RL, Childress AC, Cutler AJ, et al. Efficacy and safety of
lisdexamfetamine dimesylate in adolescents with attention-deficit/hyperactivity
disorder. J Am Acad Child Adolesc Psychiatry. 2011;50(4):395-405.
11) Childress AC et al. Long-Term Safety and Effectiveness of Lisdexamfetamine
Dimesylate in Adolescents With Attention-Deficit/Hyperactivity Disorder. Poster
presented at the 164th Annual Meeting of the APA, 14-18 May 2011, Honolulu, Hawaii.
12) Pennick M, Absorption Of Lisdexamfetamine Dimesylate And Its Enzymatic
Conversion To D-Amphetamine. Neuropsychiatric Disease and Treatment 2010;6:317-327.
13) Faraone S, Buitelaar J, Comparing the efficacy of stimulants for ADHD in
children and adolescents using meta-analysis Eur Child Adolesc Psychiatry 2009
14) Jasinski D, Krishnan S. Abuse liability and safety of oral lisdexamfetamine
dimesylate in individuals with a history of stimulant abuse. J Psychopharmacol
2009a;23:419-427.
15) VYVANSE (R) (lisdexamfetamine dimesylate) capsules, for oral use, Initial
U.S. Approval: 2007. Highlights of Prescribing Information
16) Pliszka S and the AACAP Work Group on Quality Issues. Practice Parameter For
The Assessment And Treatment Of Children And Adolescents With
Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry
2007;46(7):894-921.
17) Bloom B, Cohen RA, Freeman G. Summary health statistics for U.S. children:
National Health Interview Survey, 2010. Vital Health Stat 10. 2011;(250):1-80.
18) McCarthy S, Wilton L, Murray ML, et al. The epidemiology of
pharmacologically treated attention deficit hyperactivity disorder (ADHD) in children,
adolescents and adults in UK primary care. BMC Pediatr. 2012;12:78.
19) International Classification of Diseases, 10th ed., (ICD-10). World Health
Organization 2007:Chapter 5,F90. Accessed August 2012 at:
http://apps.who.int/classifications/icd10/browse/2010/en#/F90-F98.
20) Polanczyk G, de Lima MS, Horta BL, et al. The worldwide prevalence of ADHD:
a systematic review and metaregression analysis. Am J Psych. 2007; 164:942-948.
21) Cheon KA, Ryu YH, Kim YK et al. Dopamine transporter density in the basal
ganglia assessed with [123I]IPT SPET in children with attention deficit hyperactivity
disorder. Eur J Nucl Med Mol Imaging 2003; 30(2):306-311.
22) Cortese S, The neurobiology and genetics of Attention-Deficit/Hyperactivity
Disorder (ADHD): What every clinician should know, European Journal of Paediatric
Neurology (2012), doi:10.1016/j.ejpn.2012.01.009
23) Faraone S, Perlis R, Doyle A et al. Molecular Genetics Of Attention Deficit
Hyperactivity Disorder. Biol Psychiatry 2005; 57:1313-1323.

For further information please contact:

Investor Relations

Eric Rojas: erojas@shire.com, +1-781-482-0999

Sarah Elton-Farr: seltonfarr@shire.com, +44-1256-894157

Media

Nicole Barraud: nbarraud@shire.com, +41-22-419-4056

Gwen Fisher: gfisher@shire.com, +1-484-595-9836

ots Originaltext: Shire Pharmaceuticals Group Plc
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