Rotarix: PMS Dr. Shailesh MEHTA GSK IAPCOI meeting Mumbai, 24 th Dec 2011

Not a single case of Intussusception was reported in this study

PSUR Data of Rotarix India

India Yr of Launch 2008 till Dec death 13 cases of intussusception ( of this 1 case of blood in stools, no intussusception on USG )

India Sr No. Loc Ref NoAge ( Months )Gender Date Received by GSKEvent Text (uncoded)OCEANS Case ID 1 IN/2008/001315Male18-Sep-08ILEOCOLICINTUSSCEPTIONB A 2 IN/2009/00027N/A 13-Mar-09INTERCEPTION (INTESTINAL BLOCK)B A 3 IN/2009/000384Male3-Apr-09INTUSSUSCEPTIONB A 4 IN/2009/000555Male21-Apr-09INTUSSUSPTIONB A 5 IN/2009/000587Male30-Apr-09INTUSUSCCPTIONB A 6 IN/2009/001237Male1-Oct-09INTUSSUSCEPTIONB A 7 IN/2010/000113Female1-Feb-10INTUSSUSCEPTIONB A 8 IN/2010/000415Male18-May-10, USG ABDOMEN - BOWEL WALL EDEMA SUGGESTIVE OF ?AUTOREDUCTION OF INTUSSUSCEPTION.B A 9 IN/2010/001944Male29-Oct-10 ILEOCAECAL- COLIC INTUSSUSN REQD RESECTN ANASTOMOSIS FOR GANGRENOUS BOWEL.B A 10 IN/2010/001967Male2-Nov-10 BLOOD IN STOOLS (OVER 24 HRS ) 7-8 HRS AFTER BEING ADMINISTERED THE 2ND DOSE OF ROTARIX 6 MONTHS OF AGE.USG ABD DONE - NO INTUSSUSPTN.B A 11 IN/2011/000834Male14-Mar-11 OPERATED FOR REDUCTION OF INTUSSUCEPTIONB A 12 IN/2011/001367Male16-May-11 DIAGNOSED INTUSSUSCEPTION ON USG ABD. SURGICAL REDUCN DONEB A 13 IN/2011/001683Female2-Jul-11 31/2 MTH OLD FCH WAS ADMINISTERED RTX 1ST DOSE AT AM ON 1ST JUL"11. BABY died within 12 hrs of vaccination.B A 14 IN/2011/001705Female7-Jul-11 5 MONTH OLD BABY DEVELOPED INTUSSUSCEPTION 2 MONTHS AFTER THE 2ND DOSE OF ROTARIX VACCINE.B A

PSUR Data of Rotarix Global

PSUR Data: Worldwide (July 2004-July 2011) International Birth Date: 12 July 2004 (Mexico) 1. Data Lock Points: 12 July 2004 to 11 January cases of intussusception have been reported 2. Data Lock Points: 12 January July cases of intussusception after vaccination have been reported 3. Data Lock Points: 12 July 2006 –11 January cases of intussusception were received 4. Data Lock Points: 12 January 2007 – 11 July cases of intussusception have been received. 5. Data Lock Points: 12 July 2007 – 11 January cases of intussusception (IS) have been received during the period of this report. 6. Data Lock Points: 12 January 2008 – 11 July cases of intussusception (IS) have been received during the period of this report. 7. Data Lock Points: 12 July 2008 – 11 Jan cases of intussusception (IS) have been received during the period of this report. 8. Data Lock Points: 12 Jan 2009 – 11 Jul cases of intussusception (IS) have been received during the period of this report. 9. Data Lock Points: 12 Jul 2009 – 11 Jan cases of intussusception (IS) have been received during the period of this report. 10. Data Lock Points: 12 Jan 2010 – 11 Jul cases of intussusception (IS) have been received during the period of this report 11. Data Lock Points: 12 Jul 2010 – 11 Jul cases of intussusception (IS) have been received during the period of this report

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Global Expert Academy on Rotavirus ROT Sponsored by GlaxoSmithKline Biologicals Rotarix™ and Rotateq® active surveillance in Australia Active surveillance for IS  Two active surveillance mechanisms:  Hospital-based case findings (the Paediatric Enhanced Disease Surveillance [PAEDS] hospital-based network)  Monthly reports from paediatricians (the Australian Paediatric Surveillance Unit [APSU]) No overall increase in IS following rotavirus vaccination Evidence suggestive of an elevated risk within 21 days following the first dose only IS cases following Dose 1 in infants 1 to ≤3 months Rotarix ™RotaTeq® 1–7 days relative risk [RR]3.5 (95%CI: 0.7, 10.1)5.3 (95%CI: 1.1, 15.4) 1–21 days RR1.5 (95%CI: 0.4, 3.9)3.5 (95%CI: 1.3, 7.6) Buttery et al. Vaccine 2011, doi: /j.vaccine [in press] Rotarix is a trademark of the GlaxoSmithKline group of companies RotaTeq is a registered trademark of Merck & Co., Inc.

Global Expert Academy on Rotavirus ROT Sponsored by GlaxoSmithKline Biologicals Mexican PASS study on IS with Rotarix™: interim analysis (January 2008 – December 2009) Methods  Prospective, hospital-based active surveillance for definite IS  Conducted in 66 hospitals (Instituto Mexicano del Seguro Social) across Mexico, covering a birth cohort of approximately 500,000 infants  Assessment of temporal association between vaccination and onset of IS by self-controlled case-series analysis  Primary interim safety objective was considered met if the upper limit of the 99%CI of the relative incidence of IS within 31 days of vaccination was <4.33 for Dose 1 and <2.18 for Dose 2, corresponding to an additional risk of 2/10,000 based on experience with a previous RV vaccine (RotaShield™) Velazquez et al. Acta Pædiatrica 2010: 99(Suppl. 462): 47–120, PP106 (special issue: Abstracts from the 2 nd Excellence in Paediatrics conference, 2 – 4 Dec 2010, London, UK) Rotarix is a trademark of the GlaxoSmithKline group of companies RotaShield is a trademark of Wyeth

Global Expert Academy on Rotavirus ROT Sponsored by GlaxoSmithKline Biologicals Mexican PASS study on IS with Rotarix™: interim analysis (January 2008 – December 2009) Results  461 episodes of IS reported in 459 subjects  Clustering of IS cases within 7 days of vaccination observed post-Dose 1, but not post-Dose 2 Dose Risk period (days) IS relative incidence99% CI 10– –3.080P = – –1.873P = Velazquez et al. Acta Pædiatrica 2010: 99(Suppl. 462): 47–120, PP106 (special issue: Abstracts from the 2 nd Excellence in Paediatrics conference, 2 – 4 Dec 2010, London, UK) Rotarix is a trademark of the GlaxoSmithKline group of companies

Global Expert Academy on Rotavirus ROT Sponsored by GlaxoSmithKline Biologicals Mexican PASS study on IS with Rotarix™: Summary on the interim analysis  Based on these data, GSK concludes that the benefit/risk profile for Rotarix™ continues to be clinically acceptable  As a risk minimisation measure, the current Rotarix™ prescribing information and patient leaflets alert HCP and parents to monitor vaccinated infants for signs and symptoms of IS  Data have been shared with regulatory and supranational authorities around the world, including the EMA, the FDA, TGA, WHO and PAHO:  USA label for Rotarix™ was the first to be updated on September 17,  The corresponding label update is under review by the other Authorities 1. [accessed Sept 29 th 2010] Rotarix is a trademark of the GlaxoSmithKline group of companies

Global Expert Academy on Rotavirus ROT Sponsored by GlaxoSmithKline Biologicals Rotarix™ efficacy against severe RVGE (Rota-037, Africa) *Rotarix™ N=2,974 n (%) Placebo N=1,443 n (%) VE % (95% CI) p value Severe RVGE56 (1.9)70 (4.9)61.2 (44.0–73.2)<0.001 Infants randomly assigned into three groups (1:1:1) to receive two doses of Rotarix™ at 10 and 14 weeks of age; three doses of Rotarix™ at 6, 10, and 14 weeks of age; or three doses of placebo to test the hypothesis that infants may require three doses of vaccine in this setting HIV positive subjects not excluded Efficacy calculated from 2 weeks post-last dose of Rotarix™ /placebo until 1 year of age: according-to-protocol (ATP) cohort for efficacy *Pooled (2 doses and 3 doses) vaccine cohort N = number of subjects included in each group; n = number of subjects reporting at least one event in each group n/N (%) = percentage of subjects reporting at least one event; VE (%) = vaccine efficacy (conditional method); CI = confidence intervals Severity of RVGE was assessed using the 20-point Vesikari scale (severe RVGE ≥11) p value = two-sided Fisher’s exact test Madhi SA et al. N Engl J Med 2010; 362: 289–98 Rotarix is a trademark of the GlaxoSmithKline group of companies

Global Expert Academy on Rotavirus ROT Sponsored by GlaxoSmithKline Biologicals Burden of RV potentially prevented in Africa (Rota-037) Ruiz-Palacios GM et al. N Engl J Med 2006; 354: 11–22; Madhi SA et al. N Engl J Med 2010; 362: 289 – 98 Severe RVGE episodes prevented per 100 children per year – comparison with Latin America (and Finland) study (Rota-023) Severe RVGE episodes per 100 infant-years Placebo Vaccine

Global Expert Academy on Rotavirus ROT Sponsored by GlaxoSmithKline Biologicals OPV co-ad (six countries) severe RVGE 4 1st year FU: 81.6% (54.4–93.5) Three countries severe RVGE 5–7 1st FU: 100% (72.2–100) 2nd FU: 96.1% (85.1–99.5) 3rd FU: 100% (67.5–100.0) Two countries severe RVGE 8 1st FU: 61.2% (44.0–73.2) Six countries severe RVGE 3 1st FU: 95.8% (89.6–98.7) 2nd FU: 90.4% (85.1–94.1) 11 countries severe RVGE 1,2 1st FU: 84.7% (71.7–92.4) 2nd year FU: 80.5% (71.3–87.1) Rotarix™ global efficacy against severe RVGE Central and South America Europe South East Asia Africa References in speaker notes Co-ad, co-administration; FU, follow-up Rotarix is a trademark of the GlaxoSmithKline group of companies

Global Expert Academy on Rotavirus ROT Sponsored by GlaxoSmithKline Biologicals Rotarix™ protects against a broad range of RV types: integrated analysis of randomised control trials Any RVGESevere RVGE (≥11 Vesikari score) Vaccine efficacy (%, 95% CI) De Vos B et al. Pediat Infect Dis J 2009; 28: 261–6. Figures reproduced with permission from Lippincott Williams & Wilkins. CI, confidence intervals Meta-analysis of five studies: Rota-004 (Finland), 006 (Brazil, Mexico, Venezuela), 007 (Singapore), 023 (Latin America – 11 countries), 036 (Europe – 6 countries) G1P[8]G3P[8]G4P[8]G9P[8]G2P[4] G1P[8]G3P[8]G4P[8]G9P[8]G2P[4] 82.6% 87.7% 87.4% 90.2% 84.9% 60.6% 93.4% 83.8% 81.0% 71.4% Rotarix is a trademark of the GlaxoSmithKline group of companies

Global Expert Academy on Rotavirus ROT Sponsored by GlaxoSmithKline Biologicals G1G2G3G4G8G9G12 SourceVE [95% CI] against severe RVGE 1-year follow-up Ruiz-Palacios et al Latin America 90.8 [70–98] 45.4 [<0–86] *86.9 [63–97] *86.9 [63–97] - *86.9 [63–97] - Neuzil et al Africa 64.1 [30–82] 79.2 [9–97] 83.8 [10–98] [17–85] [<0–78] Vesikari et al Europe 96.4 [86–100] 74.7 [<0–100] 100 [45–100] 100 [65–100] [78–99] - SourceVE [95% CI] against severe RVGE 2-year follow-up Linhares et al Latin America 82.7 [64–93] 43.8 [<0–88] **82.2 [70–90] **82.2 [70–90] - **82.2 [70–90] - Phua et al Asia 100 [81–100] 100 [<0–100] 94.5 [65–100] [44–100] - Vesikari et al Europe 96.4 [90–99] 85.5 [24–99] 93.7 [53–100] 95.4 [68–100] [72–93] - *Pooled data for G3, G4 and G9. **Pooled data for P[8] non-G1 (G3, G4, G9) References in speaker notes. VE, vaccine efficacy; CI, confidence intervals Rotarix™ protects against a broad range of RV types Rotarix is a trademark of the GlaxoSmithKline group of companies