Shire's Venvanse® (lisdexamfetamine dimesylate) Marketing Application accepted for review

Shire plcShire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today announced the acceptance for review of their once-daily ADHD medicinal product VENVANSE® (lisdexamfetamine dimesylate) by the Medicines Healthcare products Regulatory Agency (MHRA), UK. The MHRA have agreed to act as the Reference Member State for this Decentralised Procedure (DCP) which will initially include eight European countries. This application follows the successful completion of the European Phase 3 study of VENVANSE in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) last year.*

VENVANSE® is the first long-acting prodrug stimulant and is currently commercialized in the US, and Canada for the treatment of ADHD in children, adolescents and adults (under the tradename VYVANSE®) and in Brazil for the treatment of ADHD in children (under the trade name VENVANSE®).

"The regulatory submission of VENVANSE in Europe is an important milestone for Shire and for physicians in the EU who are seeking alternative treatments to help their patients diagnosed with ADHD," said Mike Yasick, Senior Vice President of Shire's ADHD business unit. "VENVANSE is an approved ADHD treatment in North and South America and has become an important resource for physicians when helping their patients manage their ADHD symptoms, We look forward to making this treatment available in Europe."

About lisdexamfetamine dimesylate (1,2)
VENVANSE (LDX) is available as a prescription-only medicine in the USA (brand name VYVANSE® ; approved for the treatment of ADHD in children and adolescents aged 6 to 17 and adults), Canada (brand name VYVANSE® (available for use in children and adolescents aged 6 to 17 and adults) and Brazil (VENVANSE™; approved for children aged 6-12 years).

LDX should be used as part of a total treatment program that may include counseling or other therapies.

LDX is a prodrug of dextroamfetamine. After oral administration, LDX is rapidly absorbed from the gastrointestinal tract and hydrolyzed primarily in whole blood to dextroamfetamine, which is responsible for the drug's activity.

The safety and tolerability profiles of LDX are generally consistent with those of other CNS (central nervous system) stimulant medications, the most common side effects being decreased appetite, insomnia, abdominal pain, headache, and irritability.

VYVANSE is a stimulant medication and federally controlled substance (CII) because it can be abused or lead to dependence. Keep VYVANSE in a safe place to prevent misuse and abuse. Selling or giving away VYVANSE may harm others, and is against the law. Misuse of stimulants may cause sudden death and serious cardiovascular adverse events.

About ADHD
ADHD is one of the most common psychiatric disorders in children and adolescents.(3,4) Worldwide prevalence of ADHD is estimated at 5.3 percent.(5)

ADHD is a psychiatric behavioural 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.(6,7) The exact origin of ADHD is unknown, but scientists speculate the disorder may be caused, in part, by an imbalance of two neurotransmitters, dopamine (DA) and noradrenaline (NA), which are believed to play an important role in the ability to focus and pay attention to tasks.(8) Adequate diagnosis requires the use of medical and special psychological, educational and social resources, utilising diagnostic criteria such as Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV-TR) or International Classification of Diseases 10 (ICD-10).(6,7)

Although there is no "cure" for ADHD, there are accepted treatments that specifically target its symptoms. A multimodal treatment approach that combines medication and behavioural modifications are found to be most effective in managing ADHD.(9)

ADHD-RS-IV is a standardized, validated test for assessing symptoms of ADHD and for assessing their response to treatment. The scale, which contains 18 items, is based on the ADHD diagnostic criteria as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision®, a publication of the American Psychiatric Association.(10)

CGI is a standard assessment used to rate the severity of a patient’s illness and improvement over time.(11)

CPRS-R is a comprehensive parent-rated scale that uses observer and self-report ratings to help assess ADHD and evaluate behavioral issues in children and adolescents.(12)

CHIP-CE/PRF is a 76-item questionnaire designed to measure the health of children aged 6 to 11 years from the caregiver’s perspective, and consists of five domains (Satisfaction, Comfort, Risk Avoidance, Resilience, and Achievement) that measure structurally distinct, interrelated aspects of health.(13)

The Health Utilities Index (HUI) descriptive system focuses on impairment and classifies respondents into either HUI2 or HUI3 health states. The HUI2 consists of seven attributes (sensation, mobility, emotion, cognition, selfcare, pain and fertility), with three to five levels, leading to 24,000 possible health states.(14)

WFIRS-P is a scale to be completed by the parent/guardian of a child and evaluates how an individual is able to function; questions are framed to assess how often an individual's behaviour or emotional problems have impacted various clinically-relevant domains of functioning.(15)

About 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, human genetic therapies, gastrointestinal diseases and regenerative medicine 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.

* 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 (data from this study were publicly disclosed on October 21st at the AACAP congress 2011 in Toronto)

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