Positive Top-line Results for Vyvanse in Adults with BED

Positive Top-line Results Shown for Vyvanse® (lisdexamfetamine dimesylate)Capsules (CII) in Adults with Binge Eating Disorder Shire Plans to Submit a Supplemental New Drug Application (sNDA) by Q3 2014 05 November 2013 - Shire plc (LSE: SHP, NASDAQ: SHPG) announces positivetop-line results from two identically designed randomized placebo-controlledPhase 3 studies evaluating the efficacy and safety of Vyvanse®(lisdexamfetamine dimesylate) Capsules (CII) versus placebo in adults withbinge eating disorder (BED). In both studies Vyvanse was found to bestatistically superior to placebo on the primary efficacy analysis (p-value=5% of patients) TEAEs in patients taking Vyvanse included dry mouth, insomnia,headache, decreased appetite, nausea, irritability, heart rate increased,anxiety, feeling jittery, constipation, hyperhidrosis. Study SPD489-344 In study SPD489-344 there was 1 patient treated with Vyvanse who reported aserious adverse event (SAE); 2 patients treated with placebo-reported SAEs.There were 7 patients on Vyvanse reported TEAEs that led to studydiscontinuation; 4 patients on placebo reported TEAEs that led to studydiscontinuation. The most commonly reported (>=5% of patients) TEAEs inpatients taking Vyvanse included dry mouth, headache, insomnia, fatigue,nausea, diarrhoea, decreased appetite, constipation, feeling jittery, bloodpressure increased, and irritability. There were no deaths in either of the studies. Further evaluation of the safety information related to vital signs, ECG,clinical laboratory and other safety assessments results is currently underway. The safety profile for Vyvanse in these two studies, based on top-line data,appears to be generally consistent with the known profile established instudies in adults with ADHD. The studies consisted of a minimum 2-week screening period, a 12-week treatmentphase (4 weeks of dose-optimization and 8 weeks of maintenance), and afollow-up visit 1 week after the last on-treatment visit. During the screeningperiod, eligible patients demonstrated BED of at least moderate severity,defined in the study protocol as at least three or more binge days per week,for each of the 2 weeks prior to baseline, per diary entries. Patients wererandomized to Vyvanse or placebo treatment groups. During the dose optimizationperiod, all Vyvanse-treated patients were initiated at the 30-mg dose, and thentitrated in 20-mg increments to their optimal dose (either 50 or 70mg). Patients were excluded if they had a concurrent diagnosis of bulimia nervosa,anorexia nervosa, other psychiatric disorders, or certain medicalco-morbidities (e.g., cardiovascular risk, moderate to severe hypertension,diabetes mellitus); a Montgomery-Åsberg Depression Rating Scale (MADRS) totalscore of 18 or more at baseline visit; a lifetime history of amphetamine,cocaine, or other stimulant abuse and/or dependence. RESEARCH CRITERIA FOR BED DIAGNOSIS Both clinical trials used the Diagnostic and Statistical Manual of MentalDisorders, Fourth Edition, Text Revision (DSM-IV-TR®) research criteria forBED. DSM-IV-TR® research criteria for BED, as set forth in Appendix B (CriteriaSets and Axes Provided for Further Study), characterizes the disorder byrecurrent episodes of eating unusually large amounts of food in a short periodof time (e.g., within a 2-hour period), a sense of lack of control over the actof eating during the episode, and marked distress. BED episodes also areassociated with at least three of the following: eating more rapidly thannormal; eating until feeling uncomfortably full; eating large amounts of foodwhen not feeling physically hungry; often eating alone because of embarrassmentby how much food is being eaten; feeling disgusted with oneself, depressed orguilty after overeating. Binge eating occurs, on average, at least two days aweek for six months. The episodes of binge eating do not occur exclusivelyduring the course of bulimia nervosa or anorexia nervosa. The recently published DSM-5™ (May 2013) includes BED as a formal EatingDisorder diagnosis. DSM-5™requires that binge eating occurs on average at leastonce a week for three months. SHIRE PIPELINE UPDATE In light of the early availability of top-line data for the BED phase 3program, Shire has reviewed timelines for two other major phase 3 programs:lifitegrast in Dry Eye Disease and Vyvanse as an adjunctive treatment in MajorDepressive Disorder (MDD). The Company now anticipates that top-line data fromOPUS 2 for lifitegrast could become available before the end of 2013. TheSonata safety study for lifitegrast is scheduled for completion by mid-2014.The MDD program for Vyvanse is also on track for completion in the first halfof 2014. ABOUT Vyvanse® (lisdexamfetamine dimesylate) INDICATION Vyvanse is indicated for the treatment of ADHD in patients ages 6 and above.Efficacy was established in short-term controlled studies in children aged 6 to17 and in adults. Vyvanse is also approved as a maintenance treatment forpatients ages 6 and above with ADHD based on one maintenance study in patientsaged 6 to 17 and one maintenance study in adults. IMPORTANT SAFETY INFORMATION WARNING: ABUSE AND DEPENDENCE CNS stimulants (amphetamines and methylphenidate-containing products) have ahigh potential for abuse and dependence. Assess the risk of abuse prior to prescribing and monitor for signs of abuseand dependence while on therapy. * Contraindications: * + Known hypersensitivity to amphetamines or other ingredients in Vyvanse. Anaphylactic reactions, Stevens - Johnson syndrome, angioedema, and urticaria have been observed in postmarketing reports. + Concurrent administration of monoamine oxidase inhibitors (MAOI) or administration of Vyvanse within 14 days of the last MAOI dose. Hypertensive crisis can occur. * Educate patients about abuse and periodically re-evaluate the need for Vyvanse. * Sudden death, stroke and myocardial infarction have been reported in adults with CNS stimulant treatment at recommended doses. Sudden death has been reported in children and adolescents with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Prior to treatment assess for the presence of cardiac disease. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during Vyvanse treatment. * CNS stimulants cause an increase in blood pressure (mean increase about 2-4 mm Hg) and heart rate (mean increase about 3-6 bpm). Monitor all patients for tachycardia and hypertension. * Use of stimulants may cause psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with preexisting psychosis. Clinical evaluation for bipolar disorder is recommended prior to stimulant use. * CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Monitor weight and height in children during treatment with Vyvanse. Treatment may need to be interrupted in children not growing as expected. * Stimulants used to treat ADHD, including Vyvanse, are associated with peripheral vasculopathy, including Raynaud's phenomenon. Careful observation for digital changes (e.g., numbness, pain, skin color change, or sensitivity to temperature, and rarely ulcerations and/or soft tissue breakdown) is necessary during treatment and may require further evaluation (e.g., referral). * The most common adverse reactions (≥5% and at least twice the rate of placebo) reported in clinical trials were: * + Children aged 6 to 12: decreased appetite, insomnia, upper abdominal pain, irritability, vomiting, decreased weight, nausea, dry mouth and dizziness; + Adolescents aged 13 to 17: decreased appetite, insomnia, and decreased weight; + Adults: decreased appetite, insomnia, dry mouth, diarrhea, nausea, anxiety and anorexia. Please click here for Full Prescribing Information. 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 [email protected] +44 1256 894 280 Gwen Fisher [email protected] +1 484 595 9836 NOTES TO EDITORS Shire enables people with life-altering conditions to lead better lives. Our strategy is to focus on developing and marketing innovative specialtymedicines to meet significant unmet patient needs. We provide treatments in Neuroscience, Rare Diseases, Gastrointestinal,Internal Medicine and Regenerative Medicine, and we are developing treatmentsfor symptomatic conditions treated by specialist physicians in other targetedtherapeutic areas. www.shire.com The Vyvanse®, Elvanse®, Tyvense®, and Venvanse™ marks used in this release aretrademarks of Shire plc or companies within the Shire group. FORWARD - LOOKING STATEMENTS - "SAFEHARBOR" STATEMENT UNDER THE PRIVATESECURITIES LITIGATION REFORM ACT OF 1995 Statements included in this announcement that are not historical facts areforward-looking statements. Forward-looking statements involve a number ofrisks and uncertainties and are subject to change at any time. In the eventsuch risks or uncertainties materialize, Shire's results could be materiallyadversely affected. The risks and uncertainties include, but are not limitedto, that: * Shire's products may not be a commercial success; * revenues from ADDERALL XR are subject to generic erosion; * the failure to obtain and maintain reimbursement, or an adequate level of reimbursement, by third-party payors in a timely manner for Shire's products may impact future revenues and earnings; * Shire relies on a single source for manufacture of certain of its products and a disruption to the supply chain for those 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; * Shire uses third party manufacturers to manufacture many of its products and is reliant upon third party contractors for certain goods and services, and any inability of these third party manufacturers to manufacture products, or any failure of these third party contractors to provide these goods and services, in each case in accordance with its respective contractual obligations, could adversely affect Shire's ability to manage its manufacturing processes or to operate its business; * the development, approval and manufacturing of Shire's products is subject to extensive oversight by various regulatory agencies and regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to significant delays, increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches; * the actions of certain customers could affect Shire 's ability to sell or market products profitably and fluctuations in buying or distribution patterns by such customers could adversely impact Shire's revenues, financial conditions 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 the distraction of senior management, significant legal costs and the payment of substantial compensation or fines; * adverse outcomes in legal matters and other disputes, including Shire's ability to obtain, maintain, 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; and other risks and uncertainties detailed from time to time in Shire's filingswith the U.S. Securities and Exchange Commission, including its most recentAnnual Report on Form 10K. 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