Press Release. Registered in Jersey, No , 22 Grenville Street, St Helier, Jersey JE4 8PX

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1 Press Release Psitive Tp-line Results Shwn fr Vyvanse (lisdexamfetamine dimesylate) Capsules (CII) in Adults with Binge Eating Disrder Shire Plans t Submit a Supplemental New Drug Applicatin (snda) by Q Nvember 2013 Shire plc (LSE: SHP, NASDAQ: SHPG) annunces psitive tp-line results frm tw identically designed randmized placeb-cntrlled Phase 3 studies evaluating the efficacy and safety f Vyvanse (lisdexamfetamine dimesylate) Capsules (CII) versus placeb in adults with binge eating disrder (BED). In bth studies Vyvanse was fund t be statistically superir t placeb n the primary efficacy analysis (p-value <0.001) f the change frm baseline at weeks 11 t 12 in terms f number f binge days per week. The safety fr Vyvanse in these tw studies appears t be generally cnsistent with the knwn prfile established in studies in adults with Attentin-Deficit/Hyperactivity Disrder (ADHD). The Cmpany is reprting the data sner than riginally anticipated because f faster than expected cmpletin f bth studies. We are extremely pleased with these results, and will be wrking expeditiusly t submit an applicatin t the U.S. Fd and Drug Administratin fr a new indicatin f BED fr Vyvanse, already well established fr its efficacy and safety in ADHD, said Flemming Ornskv, M.D., Chief Executive Officer, Shire. BED is a cnditin fr which there is n currently apprved pharmaclgic treatment and yet there is significant unmet patient need, as was demnstrated with the faster than expected enrllment f participants in ur clinical trial prgram. Our develpment f Vyvanse fr BED als aligns well with Shire s grwth strategy f develping innvative treatments t address significant unmet patient needs. In additin t the psitive tp-line primary results, bth studies shwed statistically significant (p-value <0.001) and cnsistent treatment effects fr Vyvanse acrss the key secndary efficacy endpints that have been analyzed thus far in the tp-line data. These include the Clinical Glbal Impressins Glbal Imprvement (CGI-I), 4-week binge cessatin, percent change frm baseline in bdy weight, and change frm baseline in the Yale-Brwn Obsessive Cmpulsive Scale Mdified fr Binge Eating (Y-BOCS-BE). Additinal analyses cntinue fr ther secndary endpints. Shire anticipates presenting the efficacy and safety data frm bth studies at a majr scientific meeting in The cmpany plans t file fr FDA regulatry apprval f Vyvanse fr the treatment f BED in adults (ages 18 t 55) by Q Vyvanse is a prescriptin medicine currently nly apprved fr the treatment f ADHD in the United States, Canada, Australia, several Eurpean cuntries (trade name: Elvanse /Tyvense ) and Brazil (trade name: Venvanse ). Vyvanse shuld nly be used in accrdance with lcally apprved prescribing infrmatin. CNS stimulants (amphetamines and methylphenidate-cntaining prducts) have a high ptential fr abuse and dependence. Assess the risk f abuse prir t prescribing and mnitr fr signs f abuse and dependence while n therapy. BED has a lifetime prevalence f 2.8 percent in adults in the United States, and is characterized by recurring episdes f binge eating, feeling ut f cntrl while binging, and feeling guilt and shame afterward. It is frmally recgnized as a distinct psychiatric disrder in the Diagnstic and Statistical Manual f Mental Disrders (DSM-5 ). Registered in Jersey, N , 22 Grenville Street, St Helier, Jersey JE4 8PX

2 Binge eating disrder is an imprtant public health prblem that is under-recgnized, and causes great distress fr patients, said Susan L. McElry, M.D., Prfessr f Psychiatry and Behaviral Neurscience, University f Cincinnati Cllege f Medicine; and principal investigatr f bth studies. Increased awareness f binge eating disrder amng the medical cmmunity is greatly needed, as are nvel treatment strategies fr individuals suffering frm this ften secretive disrder. ABOUT THE BED STUDIES Each f the tw identically designed pivtal Phase 3, multi-center, randmized, duble-blind, parallel-grup, placeb-cntrlled, dse-ptimized studies was designed t assess the safety, efficacy, and tlerability f Vyvanse in patients aged 18 t 55 wh met DSM-IV-TR criteria fr a diagnsis f BED. Study SPD randmized 383 patients and study SPD randmized 390 patients. Patients were randmized in a 1:1 rati t Vyvanse r placeb. The primary efficacy endpint fr these studies was defined as the change frm baseline t Weeks (Visit 8) in the number f binge days per week determined by clinical interview based n participant diary data. Vyvanse was statistically superir t placeb n the primary efficacy analysis fr bth studies. Safety and tlerability evaluatins f Vyvanse included treatment-emergent adverse events (TEAEs), vital signs, weight, and electrcardigrams (ECGs). The key secndary endpints analyzed t date included CGI-I, 4-week binge cessatin, percent change frm baseline in bdy weight, and change frm baseline in Y-BOCS-BE. The CGI-I was dichtmized as imprved (including categries f very much imprved and much imprved ) r nt imprved (ther categries excluding nt assessed ). The endpint 4-week cessatin f binge eating is defined as n binge episdes fr 28 cnsecutive days prir t the last study visit. The Y-BOCS-BE is a mdified versin f Yale-Brwn Obsessive Cmpulsive Scale that measures the bsessin f binge eating thughts and cmpulsiveness f binge eating behavirs. Vyvanse was statistically superir t placeb n the key secndary efficacy endpints analyzed t date fr bth studies. Study SPD In study SPD there were 3 patients treated with Vyvanse wh reprted serius adverse events (SAEs); 2 patients treated with placeb reprted SAEs. There were 12 patients n Vyvanse wh reprted treatment-emergent adverse events (TEAEs) that led t study discntinuatin; 5 patients n placeb reprted TEAEs that led t study discntinuatin. The mst cmmnly reprted (>=5% f patients) TEAEs in patients taking Vyvanse included dry muth, insmnia, headache, decreased appetite, nausea, irritability, heart rate increased, anxiety, feeling jittery, cnstipatin, hyperhidrsis. Study SPD In study SPD there was 1 patient treated with Vyvanse wh reprted a serius adverse event (SAE); 2 patients treated with placeb-reprted SAEs. There were 7 patients n Vyvanse reprted TEAEs that led t study discntinuatin; 4 patients n placeb reprted TEAEs that led t study discntinuatin. The mst cmmnly reprted (>=5% f patients) TEAEs in patients taking Vyvanse included dry muth, headache, insmnia, fatigue, nausea, diarrhea, decreased appetite, cnstipatin, feeling jittery, bld pressure increased, and irritability. There were n deaths in either f the studies. Further evaluatin f the safety infrmatin related t vital signs, ECG, clinical labratry and ther safety assessments results is currently underway. 2

3 The safety prfile fr Vyvanse in these tw studies, based n tp-line data, appears t be generally cnsistent with the knwn prfile established in studies in adults with ADHD. The studies cnsisted f a minimum 2-week screening perid, a 12-week treatment phase (4 weeks f dse-ptimizatin and 8 weeks f maintenance), and a fllw-up visit 1 week after the last n-treatment visit. During the screening perid, eligible patients demnstrated BED f at least mderate severity, defined in the study prtcl as at least three r mre binge days per week, fr each f the 2 weeks prir t baseline, per diary entries. Patients were randmized t Vyvanse r placeb treatment grups. During the dse ptimizatin perid, all Vyvanse-treated patients were initiated at the 30-mg dse, and then titrated in 20-mg increments t their ptimal dse (either 50 r 70mg). Patients were excluded if they had a cncurrent diagnsis f bulimia nervsa, anrexia nervsa, ther psychiatric disrders, r certain medical c-mrbidities (e.g., cardivascular risk, mderate t severe hypertensin, diabetes mellitus); a Mntgmery-Åsberg Depressin Rating Scale (MADRS) ttal scre f 18 r mre at baseline visit; a lifetime histry f amphetamine, ccaine, r ther stimulant abuse and/r dependence. RESEARCH CRITERIA FOR BED DIAGNOSIS Bth clinical trials used the Diagnstic and Statistical Manual f Mental Disrders, Furth Editin, Text Revisin (DSM-IV-TR ) research criteria fr BED. DSM-IV-TR research criteria fr BED, as set frth in Appendix B (Criteria Sets and Axes Prvided fr Further Study), characterizes the disrder by recurrent episdes f eating unusually large amunts f fd in a shrt perid f time (e.g., within a 2-hur perid), a sense f lack f cntrl ver the act f eating during the episde, and marked distress. BED episdes als are assciated with at least three f the fllwing: eating mre rapidly than nrmal; eating until feeling uncmfrtably full; eating large amunts f fd when nt feeling physically hungry; ften eating alne because f embarrassment by hw much fd is being eaten; feeling disgusted with neself, depressed r guilty after vereating. Binge eating ccurs, n average, at least tw days a week fr six mnths. The episdes f binge eating d nt ccur exclusively during the curse f bulimia nervsa r anrexia nervsa. The recently published DSM-5 (May 2013) includes BED as a frmal Eating Disrder diagnsis. DSM-5 requires that binge eating ccurs n average at least nce a week fr three mnths. SHIRE PIPELINE UPDATE In light f the early availability f tp-line data fr the BED phase 3 prgram, Shire has reviewed timelines fr tw ther majr phase 3 prgrams: lifitegrast in Dry Eye Disease and Vyvanse as an adjunctive treatment in Majr Depressive Disrder (MDD). The Cmpany nw anticipates that tp-line data frm OPUS 2 fr lifitegrast culd becme available befre the end f The Snata safety study fr lifitegrast is scheduled fr cmpletin by mid The MDD prgram fr Vyvanse is als n track fr cmpletin in the first half f

4 ABOUT Vyvanse (lisdexamfetamine dimesylate) INDICATION Vyvanse is indicated fr the treatment f ADHD in patients ages 6 and abve. Efficacy was established in shrt-term cntrlled studies in children aged 6 t 17 and in adults. Vyvanse is als apprved as a maintenance treatment fr patients ages 6 and abve with ADHD based n ne maintenance study in patients aged 6 t 17 and ne maintenance study in adults. IMPORTANT SAFETY INFORMATION WARNING: ABUSE AND DEPENDENCE CNS stimulants (amphetamines and methylphenidate-cntaining prducts) have a high ptential fr abuse and dependence. Assess the risk f abuse prir t prescribing and mnitr fr signs f abuse and dependence while n therapy. Cntraindicatins: Knwn hypersensitivity t amphetamines r ther ingredients in Vyvanse. Anaphylactic reactins, Stevens - Jhnsn syndrme, angiedema, and urticaria have been bserved in pstmarketing reprts. Cncurrent administratin f mnamine xidase inhibitrs (MAOI) r administratin f Vyvanse within 14 days f the last MAOI dse. Hypertensive crisis can ccur. Educate patients abut abuse and peridically re-evaluate the need fr Vyvanse. Sudden death, strke and mycardial infarctin have been reprted in adults with CNS stimulant treatment at recmmended dses. Sudden death has been reprted in children and adlescents with structural cardiac abnrmalities and ther serius heart prblems taking CNS stimulants at recmmended dses fr ADHD. Prir t treatment assess fr the presence f cardiac disease. Avid use in patients with knwn structural cardiac abnrmalities, cardimypathy, serius heart arrhythmia, crnary artery disease, and ther serius heart prblems. Further evaluate patients wh develp exertinal chest pain, unexplained syncpe, r arrhythmias during Vyvanse treatment. CNS stimulants cause an increase in bld pressure (mean increase abut 2-4 mm Hg) and heart rate (mean increase abut 3-6 bpm). Mnitr all patients fr tachycardia and hypertensin. Use f stimulants may cause psychtic r manic symptms in patients with n prir histry, r exacerbatin f symptms in patients with preexisting psychsis. Clinical evaluatin fr biplar disrder is recmmended prir t stimulant use. CNS stimulants have been assciated with weight lss and slwing f grwth rate in pediatric patients. Mnitr weight and height in children during treatment with Vyvanse. Treatment may need t be interrupted in children nt grwing as expected. Stimulants used t treat ADHD, including Vyvanse, are assciated with peripheral vasculpathy, including Raynaud's phenmenn. Careful bservatin fr digital changes (e.g., numbness, pain, skin clr change, r sensitivity t temperature, and rarely ulceratins and/r sft tissue breakdwn) is necessary during treatment and may require further evaluatin (e.g., referral). The mst cmmn adverse reactins ( 5% and at least twice the rate f placeb) reprted in clinical trials were: Children aged 6 t 12: decreased appetite, insmnia, upper abdminal pain, irritability, vmiting, decreased weight, nausea, dry muth and dizziness; 4

5 Adlescents aged 13 t 17: decreased appetite, insmnia, and decreased weight; Adults: decreased appetite, insmnia, dry muth, diarrhea, nausea, anxiety and anrexia. Please click here fr Full Prescribing Infrmatin. Fr further infrmatin please cntact: Investr Relatins Eric Rjas erjas@shire.cm Sarah Eltn-Farr seltnfarr@shire.cm Media Jessica Mann jmann@shire.cm Gwen Fisher gfisher@shire.cm NOTES TO EDITORS Shire enables peple with life-altering cnditins t lead better lives. Our strategy is t fcus n develping and marketing innvative specialty medicines t meet significant unmet patient needs. We prvide treatments in Neurscience, Rare Diseases, Gastrintestinal, Internal Medicine and Regenerative Medicine, and we are develping treatments fr symptmatic cnditins treated by specialist physicians in ther targeted therapeutic areas. The Vyvanse, Elvanse, Tyvense, and Venvanse marks used in this release are trademarks f Shire plc r cmpanies within the Shire grup. FORWARD - LOOKING STATEMENTS - "SAFEHARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995 Statements included in this annuncement that are nt histrical facts are frward-lking statements. Frward-lking statements invlve a number f risks and uncertainties and are subject t change at any time. In the event such risks r uncertainties materialize, Shire s results culd be materially adversely affected. The risks and uncertainties include, but are nt limited t, that: Shire s prducts may nt be a cmmercial success; revenues frm ADDERALL XR are subject t generic ersin; the failure t btain and maintain reimbursement, r an adequate level f reimbursement, by third-party payrs in a timely manner fr Shire's prducts may impact future revenues and earnings; Shire relies n a single surce fr manufacture f certain f its prducts and a disruptin t the supply chain fr thse prducts may result in Shire being unable t 5

6 cntinue marketing r develping a prduct r may result in Shire being unable t d s n a cmmercially viable basis; Shire uses third party manufacturers t manufacture many f its prducts and is reliant upn third party cntractrs fr certain gds and services, and any inability f these third party manufacturers t manufacture prducts, r any failure f these third party cntractrs t prvide these gds and services, in each case in accrdance with its respective cntractual bligatins, culd adversely affect Shire s ability t manage its manufacturing prcesses r t perate its business; the develpment, apprval and manufacturing f Shire s prducts is subject t extensive versight by varius regulatry agencies and regulatry apprvals r interventins assciated with changes t manufacturing sites, ingredients r manufacturing prcesses culd lead t significant delays, increase in perating csts, lst prduct sales, an interruptin f research activities r the delay f new prduct launches; the actins f certain custmers culd affect Shire 's ability t sell r market prducts prfitably and fluctuatins in buying r distributin patterns by such custmers culd adversely impact Shire s revenues, financial cnditins r results f peratins; investigatins r enfrcement actin by regulatry authrities r law enfrcement agencies relating t Shire s activities in the highly regulated markets in which it perates may result in the distractin f senir management, significant legal csts and the payment f substantial cmpensatin r fines; adverse utcmes in legal matters and ther disputes, including Shire s ability t btain, maintain, enfrce and defend patents and ther intellectual prperty rights required fr its business, culd have a material adverse effect n Shire s revenues, financial cnditin r results f peratins; and ther risks and uncertainties detailed frm time t time in Shire s filings with the U.S. Securities and Exchange Cmmissin, including its mst recent Annual Reprt n Frm 10K. 6