SHIRE PLC: Elvanse(R): Positive European Outcome

Positive response from European regulatory procedure supports
approval of Elvanse®(lisdexamfetamine dimesylate) for ADHD 
NYON, Switzerland - 18 December 2012 - Shire plc (LSE: SHP, NASDAQ: SHPG) today
announces a positive outcome from the European Decentralised Procedure (DCP)
for Elvanse® (to be known as Tyvense® 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®,
for the treatment of ADHD in children, adolescents and adults, and in Brazil
under the trade name Venvanse®, 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.


   
  * Tell your doctor if you or your child has any heart problems, heart 


    defects, high blood pressure, or a family history of these problems. Call
    your doctor right away if you or your child has any sign of heart problems
    such as chest pain, shortness of breath, or fainting while taking Elvanse.
      * 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


   
  * Tell your doctor about any mental problems you or your child has, or about 


    a family history of suicide, bipolar illness, or depression.
      * Call your doctor right away if you or your child has any new or worsening
    mental symptoms or problems while taking Elvanse, especially:
      * seeing or hearing things that are not real
      * believing things that are not real
      * being suspicious
      * Elvanse may cause serious side effects, including:
      * slowing of growth (height and weight) in children. Your child should have
    his or her height and weight checked often while taking Elvanse. The doctor
    may stop treatment if a problem is found during these check-ups.
      * seizures, mainly in people with a history of seizures
      * eyesight changes or blurred vision
      * worsening of sudden, repeated movements or sounds (tics) and Tourette's
    syndrome in people who already have these problems
      * The most common side effects reported in studies of Elvanse were:
      * anxiety
      * decreased appetite
      * diarrhoea
      * dizziness
      * dry mouth
      * irritability
      * loss of appetite
      * nausea
      * trouble sleeping
      * upper stomach pain
      * vomiting
      * weight loss


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) 
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  
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:
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 American
    Academy Of Child And Adolescent Psychiatry (AACAP) And The Canadian Academy
    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 ® (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.


                                                                             
Registered in Jersey, No. 99854, 22 Grenville Street, St Helier, Jersey JE4 8PX 
Press Release                                      
                                              
www.shire.com                                      
END 
-0- Dec/18/2012 14:00 GMT
 
 
Press spacebar to pause and continue. Press esc to stop.