Shire Reports Positive Phase 2 Study Met Primary End Point for Investigative Use of Vyvanse® (lisdexamfetamine dimesylate) Capsules, (CII) in Adults with Binge Eating Disorder

PHILADELPHIA, April 26, 2012 /PRNewswire/ --

Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today announced positive top-line results from a Phase 2 study to evaluate the safety and efficacy of Vyvanse^® (lisdexamfetamine dimesylate) Capsules, (CII) in adults with binge eating disorder. Following discussions with the US Food and Drug Administration (FDA), Shire plans to conduct additional larger studies to confirm the validity of the findings.

The primary objective of the study was to evaluate the efficacy of 30, 50 or 70 mg of Vyvanse compared to placebo in the treatment of binge eating disorder at Week 11 as measured by the number of binge days per week as assessed by clinical interview based on patient diary. A binge day was defined as a day during which at least one binge episode occurred. The primary study end point was the change from baseline to Week 11 in log transformed (number of binge days per week + 1). Vyvanse 50 mg and 70 mg were statistically superior to placebo on the primary end point. Vyvanse 30 mg was not statistically superior to placebo on the primary end point, clarifying the dose range for future trials in this patient population.

Vyvanse is a prescription medicine currently approved in the US and Canada, as well as in Brazil under the name Venvanse, for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). Vyvanse should only be used to treat ADHD.

Vyvanse is a Schedule II controlled substance. Stimulants, such as amphetamines and methylphenidates, are subject to misuse, abuse, addiction, and criminal diversion. Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events.

The Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition,Text Revision (DSM-IV-TR^®) research criteria for binge eating disorder, as set forth in Appendix B (Criteria Sets and Axes Provided for Further Study), characterizes the disorder by recurrent episodes of eating unusually large amounts of food in a short period of time (eg, within a 2-hour period), and a sense of lack of control over the act of eating during the episode. Binge eating disorder episodes also are associated with at least three of the following: eating more rapidly than normal; eating until feeling uncomfortably full; eating large amounts of food when not feeling physically hungry; often eating alone because of embarrassment by how much food is being eaten; feeling disgusted with oneself, depressed or feeling guilty after overeating. Binge eating occurs, on average, at least two days a week for six months. In addition, marked distress regarding binge eating is present. The episodes of binge eating do not occur exclusively during the course of bulimia nervosa or anorexia nervosa.

"Binge eating disorder is a serious condition for which there is no FDA-approved pharmacologic treatment," said Jeffrey Jonas, M.D., Senior Vice President of Research and Development for Shire's Specialty Pharmaceuticals and Regenerative Medicine Businesses. "We plan to use these results to work with regulatory agencies to determine our path forward for completing a clinical development program for Vyvanse as a treatment for patients suffering with binge eating disorder. After reviewing our data we will also explore opportunities for identifying biomarkers to aid in the diagnosis and treatment of patients with binge eating disorder."

Susan McElroy, MD, Chief Research Officer, Lindner Center of HOPE and Professor of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine said, "Binge eating disorder is a common and serious condition. Given the lack of any approved pharmacologic treatment, physicians often find it difficult to design effective treatment plans for patients suffering from binge eating disorder. Shire's commitment to research with Vyvanse in this area is encouraging for those afflicted with binge eating disorder."

ABOUT THE STUDY

This Phase 2, multi-center, randomized, double-blind, parallel-group, placebo-controlled, forced-dose titration study assessed the efficacy, safety and tolerability of Vyvanse in 270 adults aged 18 to 55 who met DSM-IV-TR^® criteria for a diagnosis of binge eating disorder. The study consisted of a two-week screening period, an 11-week double-blind treatment phase and a one-week follow-up phase.

During the two-week screening period, patients recorded their binge eating episodes in a diary for at least 14 days. Eligible patients who had binge eating disorder of at least moderate severity, defined as at least three or more binge days/week for two weeks prior to their baseline visit, entered the double-blind treatment phase which consisted of a three-week forced-dose titration period and an eight-week dose-maintenance period. Patients were randomized to one of four treatment groups: Vyvanse 30, 50, or 70 mg/day or placebo. During the forced-dose titration period, all Vyvanse-treated patients initiated the study at the 30 mg dosage, and those assigned to the 50 mg and 70 mg doses had their dose titrated in 20 mg increments over a one or two week period, respectively.

Patients were excluded from the study if they had concurrent symptoms of bulimia nervosa or anorexia nervosa, other current comorbid psychiatric disorders, Montgomery-Åsberg Depression Rating Scale (MADRS) total score of 18 or more at baseline visit, a lifetime history of amphetamine, cocaine, or other stimulant abuse and/or dependence. In addition, certain medical comorbidities were excluded (eg, cardiovascular risk, moderate to severe hypertension, diabetes mellitus, etc.).

Vyvanse 50 mg and 70 mg were statistically superior to placebo on the primary end point. Vyvanse 30 mg was not statistically superior to placebo on the primary end point.

The study also evaluated the safety and tolerability of Vyvanse 30, 50 and 70 mg doses based on occurrence of treatment-emergent adverse events (TEAEs), vital signs, weight, clinical laboratory results, electrocardiogram (ECG) results, and the Columbia-Suicide Severity Rating Scale (C-SSRS).

The safety profile based on currently available data seen in this study was generally consistent with the known profile of studies of Vyvanse in adults with ADHD. Most commonly (>5%) reported TEAEs in subjects taking Vyvanse included dry mouth, decreased appetite, insomnia, headache, nausea, constipation, nasopharyngitis, decreased weight, and irritability. There were three serious adverse events (SAEs), including one with the outcome of death, in patients treated with Vyvanse. None were judged by the investigator to be related to the study drug. No SAEs were reported in patients taking placebo. Seven patients on Vyvanse had TEAEs that led to study discontinuation; none on placebo. No new safety trends were observed in regards to early discontinuation due to TEAEs. Shire is still evaluating the safety information related to discontinuation rates, vital signs, ECG and clinical laboratory results.

ABOUT VYVANSE (lisdexamfetamine dimesylate)

INDICATION

Vyvanse is a prescription medicine for the treatment of ADHD in children ages 6 to 17 and adults. Vyvanse should be used as part of a total treatment program that may include counseling or other therapies.

IMPORTANT SAFETY INFORMATION

Vyvanse has a risk of abuse or dependence. Keep in a safe place to prevent misuse and abuse. Selling or sharing Vyvanse may harm others and is illegal. Vyvanse is a stimulant. Misuse of stimulants may cause sudden death and serious heart problems.

• Do not take Vyvanse 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 Vyvanse:

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 Vyvanse.

Mental (psychiatric) problems including:

Children, Teenagers, and Adults

• new or worse behavior and thought problems
• new or worse bipolar illness
• new or worse aggressive behavior 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 Vyvanse, especially:

• seeing or hearing things that are not real
  • believing things that are not real
  • being suspicious
• Vyvanse 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 Vyvanse. 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 Vyvanse were:
  • anxiety
  • decreased appetite
  • diarrhea
  • 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 click here forFull Prescribing Information and Medication Guide, including Warning about Potential for Abuse, and discuss with your doctor.

Notes to editors

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.

For further information on Shire, please visit the Company's website: http://www.shire.com.

Vyvanse^® is a registered trademark of Shire LLC.

Venvanse is a deposited trademark in Brazil.

"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.

For further information please contact:

Investor Relations
Eric Rojas, [email protected], +1-781-482-0999
Sarah Elton-Farr, [email protected], +44-1256-894157

Media
Jessica Mann (Corporate), [email protected], +44-1256-894-280
Gwen Fisher (Specialty Pharma), [email protected], +1-484-595-9836

SOURCE Shire plc