ZUG, Switzerland – Shire plc (LSE: SHP, NASDAQ: SHPG) today announced that the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of the once-daily, non-stimulant INTUNIV® (guanfacine hydrochloride extended release; GXR) for the treatment of attention deficit/hyperactivity disorder (ADHD) in children and adolescents.
The CHMP’s positive opinion is based on results from three Phase 3 pivotal studies investigating the short- and long-term safety and efficacy of INTUNIV® in children and adolescents with ADHD.1-3
“This positive opinion from the CHMP is an important step towards providing physicians with a new therapeutic option for children and adolescents with ADHD,” said Philip J. Vickers, Ph.D., Head of Research and Development, Shire. “Due to the varying needs of patients and the different manifestations of ADHD, non-stimulant medications are an important treatment option for some patients in Europe.”
The European Commission will now consider the CHMP positive opinion in its decision of whether to grant marketing authorisation for INTUNIV® in Europe.
About ADHD in children and adolescents
ADHD is a common psychiatric disorder in children and adolescents4,5 and is recognised by the World Health Organization (WHO).6 The core symptoms are inattention, hyperactivity and impulsivity.6-8 In Europe, the prevalence of ADHD is estimated to be approximately 5% for children and adolescents (<18 years).4,5 While the exact origin of ADHD is not known, studies have indicated that ADHD could be associated with certain structural and functional brain abnormalities.9-21
If approved in Europe, INTUNIV® will be indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents 6 to 17 years old for whom stimulants are not suitable, not tolerated or have been shown to be ineffective.
If approved, INTUNIV® must be used as a part of a comprehensive ADHD treatment programme, typically including psychological, educational and social measures.
INTUNIV® contains the active substance guanfacine, a selective alpha-2A adrenergic receptor agonist.22 Studies have suggested that guanfacine may exert physiological effects by stimulating the alpha-2A adrenergic receptor in the prefrontal cortex.23,24 This region is known to control several cognitive functions including attention and social behaviours,25-27 and has been associated with some structural and functional abnormalities in individuals with ADHD.10-12
Summary of the safety outcomes of the three Phase 3 pivotal studies
Hervas et al.1
The majority of treatment-emergent adverse events (TEAEs) reported across all treatment groups were mild-to-moderate in intensity. The most common TEAEs in the GXR group included somnolence, headache and fatigue. The most common TEAEs reported in the placebo group were headache, fatigue and somnolence. TEAEs leading to study discontinuation were reported in 7.9% and 0.9% of subjects in the GXR and placebo groups, respectively. There were no clinically meaningful changes in ECG and QTc events detected, and the impact on blood pressure and pulse were consistent with known effects and were unremarkable.1
Wilens et al.2,28
The majority of adverse events (AEs) were mild-to-moderate in severity, with the most common TEAEs among those receiving GXR being somnolence, headache, fatigue and dizziness. TEAEs that led to study discontinuation were reported by 9 patients receiving GXR and 3 patients receiving placebo. There were no clinically meaningful differences between GXR and placebo on the impact on blood pressure, pulse, ECG results or QTc-related parameters. With GXR, non-significant improvements were observed in child-rated daytime sleepiness on the PDSS and non-significant child-rated improvements in behavioural and emotional symptoms on the BPRS-C scale at endpoint.2,28
Newcorn et al.3,29
TEAEs in the open-label phase led to discontinuation in 8.0% of patients. Sedative events (somnolence, sedation and hypersomnia) were reported by 53.6% of the patients. 8.7% of sedative events led to dose reduction, and 2.7% of sedative events led to study discontinuation. At the end of the randomised double-blind treatment period, the majority of reported TEAEs were mild-to-moderate in intensity. The most common TEAEs included headache and somnolence. TEAEs that led to study discontinuation were reported by 3 (1.9%) patients receiving GXR (grand mal convulsion, sedation and somnolence) and 2 (1.3%) patients receiving placebo. Blood pressure and pulse observed in this study were consistent with the known profile of GXR and GXR was not associated with any clinically significant changes in ECG parameters, height or weight.3
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NOTES TO EDITORS
Shire enables people with life-altering conditions to lead better lives.
Our strategy is to focus on developing and marketing innovative specialty medicines to meet significant unmet patient needs.
We focus on providing treatments in Rare Diseases, Neuroscience, Gastrointestinal and Internal Medicine and we are developing treatments for symptomatic conditions treated by specialist physicians in other targeted therapeutic areas, such as Ophthalmics.
THE “SAFE HARBOR” STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
Statements included in this announcement 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, Shire’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, that:
- Shire’s products may not be a commercial success;
- product sales from ADDERALL XR® and INTUNIV® are subject to generic competition;
- the failure to obtain and maintain reimbursement, or an adequate level of reimbursement, by third-party payers in a timely manner for Shire's products may affect future revenues, financial condition and results of operations;
- Shire conducts its own manufacturing operations for certain of its products and is reliant on third-party contract manufacturers to manufacture other products and to provide goods and services. Some of Shire’s products or ingredients are only available from a single approved source for manufacture. Any disruption to the supply chain for any of Shire’s products may result in Shire being unable to continue marketing or developing a product or may result in Shire being unable to do so on a commercially viable basis for some period of time;
- the manufacture of Shire’s products is subject to extensive oversight by various regulatory agencies. Regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
- Shire has a portfolio of products in various stages of research and development. The successful development of these products is highly uncertain and requires significant expenditures and time, and there is no guarantee that these products will receive regulatory approval;
- the actions of certain customers could affect Shire's ability to sell or market products profitably. Fluctuations in buying or distribution patterns by such customers can adversely affect Shire’s revenues, financial condition or results of operations;
- investigations or enforcement action by regulatory authorities or law enforcement agencies relating to Shire’s activities in the highly regulated markets in which it operates may result in significant legal costs and the payment of substantial compensation or fines;
- adverse outcomes in legal matters and other disputes, including Shire’s ability to enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on Shire’s revenues, financial condition or results of operations;
- Shire faces intense competition for highly qualified personnel from other companies and organizations. Shire is undergoing a corporate reorganization and was the subject of an unsuccessful acquisition proposal and the consequent uncertainty could adversely affect Shire’s ability to attract and/or retain the highly skilled personnel needed for Shire to meet its strategic objectives;
- failure to achieve Shire’s strategic objectives with respect to the acquisition of NPS Pharmaceuticals Inc. may adversely affect Shire’s financial condition and results of operations;
- and other risks and uncertainties detailed from time to time in Shire’s filings with the U.S. Securities and Exchange Commission, including its most recent Annual Report on Form 10-K.
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29. DoF INT/SPD503-020/v2, Shire Pharmaceuticals, July 2015