18th Dec 2012 14:00
SHIRE PLC - Elvanse(R): Positive European OutcomeSHIRE PLC - Elvanse(R): Positive European Outcome
PR Newswire
London, December 18
Positive response from European regulatory procedure supportsapproval of Elvanse®(lisdexamfetamine dimesylate) for ADHD
NYON, Switzerland - 18 December 2012 - Shire plc (LSE: SHP, NASDAQ: SHPG) todayannounces a positive outcome from the European Decentralised Procedure (DCP)for Elvanse® (to be known as Tyvense® in Ireland). Elvanse is indicated as partof a comprehensive treatment programme for attention deficit/hyperactivitydisorder (ADHD) in children aged 6 years of age and over when response toprevious methylphenidate treatment is considered clinically inadequate.(1)
The UK Medicines and Healthcare products Regulatory Agency (MHRA) acted as theReference Member State on behalf of seven other European countriesparticipating in the procedure (Denmark, Finland, Germany, Ireland, Norway,Spain and Sweden). Product labelling has been agreed by these countries, whichwill now issue their national Marketing Authorisations (approvals); thistypically takes a further one to three months. In some countries, negotiationswith national pricing and reimbursement authorities will now be required beforethe medicine is made available to patients, and the timing for this processvaries between countries.
Elvanse was accepted for review by the MHRA in January 2012, with theapplication based on two European Phase 3 studies in children and adolescentswith 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 symptomsof ADHD.(2,3) Elvanse is the first of a new class of dopamine modulators approvedin 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 Brazilunder the trade name Venvanse®, for the treatment of ADHD in children aged 6 to12 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 andElvanse 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 nowimminent," said Angus Russell, CEO, Shire. "ADHD is one of the most commonpsychiatric disorders affecting children and adolescents. As all ADHD patientsare different and will vary in their responses to the available treatments, webelieve introducing Elvanse will provide physicians with a broader range ofoptions to help patients with ADHD manage their individual needseffectively. We will now work closely with the pricing and reimbursementauthorities in the respective countries to ensure that Elvanse is madeavailable to patients as soon as possible."
About Elvanse
Elvanse (lisdexamfetamine dimesylate) has not yet received national marketingauthorisation in each respective EU country involved in the DCP, and nationallicenses are expected to be issued one to three months after DCP closure. It isalready available in the USA and Canada (brand name Vyvanse) and in Brazil(brand name Venvanse), where it has been used to treat over 4 millionpatients.(4) Elvanse's efficacy and tolerability have been studied in clinicaltrials both in the USA and Europe.(2,3,5-11)
Elvanse is a single daily dose prodrug medication for the treatment of ADHD. Aprodrug is a substance that is ingested in an inactive form and then activatedwithin the body.(12)
The inactive prodrug is absorbed from the gut into the bloodstream where it isgradually converted to the active part of the medicine, d-amfetamine(d-AMF).12 The active part of Elvanse is thought to work by increasing thelevels of neurotransmitters (chemicals that are stored in nerve cells in thebrain 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 tohelp patients achieve control of their ADHD symptoms throughout the day.(14)
Indication(1)
Elvanse is indicated as part of a comprehensive treatment programme forattention deficit/hyperactivity disorder (ADHD) in children aged 6 years andover when response to previous methylphenidate treatment is consideredclinically inadequate.
Treatment must be under the supervision of a specialist in childhood and/oradolescent behavioural disorders. Diagnosis should be made according to DSM-IVcriteria or the guidelines in ICD-10 and should be based on a complete historyand evaluation of the patient. Diagnosis cannot be made solely on the presenceof one or more symptom.
The specific aetiology of this syndrome is unknown, and there is no singlediagnostic test. Adequate diagnosis requires the use of medical and specialisedpsychological, educational, and social resources.
A comprehensive treatment programme typically includes psychological,educational and social measures as well as pharmacotherapy and is aimed atstabilising children with a behavioural syndrome characterised by symptomswhich may include chronic history of short attention span, distractibility,emotional lability, impulsivity, moderate to severe hyperactivity, minorneurological 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 thedrug must be based on a very thorough assessment of the severity and chronicityof 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 interventionis generally necessary. The use of Elvanse should always be used in this wayaccording 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 336children and adolescents aged 6 to 17 years. Results of this study have beenaccepted for publication in European Neuropsychopharmacology and were alsopresented on October 21st 2011 at the American Academy of Child and AdolescentPsychiatry (AACAP) congress in Toronto.
Study 326:(3)A Phase 3, double blind, placebo-controlled, randomized withdrawal,multicentre, extension, safety and efficacy study of lisdexamfetaminedimesylate in 276 children and adolescents aged 6-17 with attention-deficit/hyperactivity disorder. Results from this study were presented on October 13th2012 at the European College of Neuropsychopharmacology (ECNP) congress inVienna.
Misuse and abuse(1)
Stimulants including Elvanse have a potential for abuse, misuse, dependence, ordiversion for non-therapeutic uses that physicians should consider whenprescribing this product. Stimulants should be prescribed cautiously topatients 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 hostilityChildren 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 lossThis is not a complete summary of safety information. For additional safetyinformation please see the Elvanse patient information leaflet or discuss withyour doctor. Please note that this safety information reflects the US labelwhich is different from the European indication.
About ADHD
Attention Deficit Hyperactivity Disorder (ADHD) is one of the most commonpsychiatric disorders in children and adolescents(16,17,18) and is recognised bythe World Health Organization (WHO).(19)
Globally, ADHD affects around 5% of children and adolescents.(20) Based on thisprevalence rate, one can estimate that 5 million young people in the EU aresuffering from ADHD.
What causes ADHD?
While the exact origin of ADHD is not known, it is thought that the disordermay be caused by an imbalance of neurotransmitters (or chemicals in thebrain).(21)
ADHD is thought to result from complex interactions between genetic andenvironmental factors,(22) with studies estimating that genetic factors explain60 to 75% of the aetiology of ADHD.(22,23)
Environmental factors which may increase the risk of developing ADHD includelow birth weight/prematurity, maternal smoking during pregnancy, and severeearly psychosocial adversity (e.g. children who have survived deprivedinstitutional care).(22)
For further information please contact:
Investor Relations Eric Rojas [email protected] +1 781 482 0999Sarah Elton-Farr [email protected] +44 1256 894157 Media Nicole Barraud [email protected] + 41 22 419 4056 Gwen Fisher [email protected] +1 484 595 9836 Notes to editorsShire enables people with life-altering conditions to lead better lives.
Through our deep understanding of patients' needs, we develop and providehealthcare in the areas of:
* Behavioral Health and Gastro Intestinal conditions * Rare Diseases * Regenerative Medicineas well as other symptomatic conditions treated by specialist physicians.
We aspire to imagine and lead the future of healthcare, creating value forpatients, 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 OF1995
Statements included herein that are not historical facts are forward-lookingstatements. Such forward-looking statements involve a number of risks anduncertainties and are subject to change at any time. In the event such risks oruncertainties materialize, the Company's results could be materially adverselyaffected. The risks and uncertainties include, but are not limited to, risksassociated with: the inherent uncertainty of research, development, approval,reimbursement, manufacturing and commercialization of the Company's SpecialtyPharmaceuticals, Human Genetic Therapies and Regenerative Medicine products, aswell as the ability to secure new products for commercialization and/ordevelopment; government regulation of the Company's products; the Company'sability to manufacture its products in sufficient quantities to meet demand;the impact of competitive therapies on the Company's products; the Company'sability to register, maintain and enforce patents and other intellectualproperty rights relating to its products; the Company's ability to obtain andmaintain government and other third-party reimbursement for its products; andother risks and uncertainties detailed from time to time in the Company'sfilings 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.
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