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 2011 1 death 13 cases of intussusception ( of this 1 case of blood in stools , no intussusception on USG )

Sr No.

1 2 3 4 5 6 7 8

Loc Ref No

IN/2008/00131 IN/2009/00027 IN/2009/00038 IN/2009/00055 IN/2009/00058 IN/2009/00123 IN/2010/00011 IN/2010/00041 9 IN/2010/00194 10 11 12 13 IN/2010/00196 IN/2011/00083 IN/2011/00136 IN/2011/00168 14 IN/2011/00170

Age ( Months )

5 N/A 4 7 3 5 7

Gender

Male N/A Male Male Male Male Female 5 4 7 4 7 3 5 Male Male Male Male Male Female Female

India

Date Received by GSK

18-Sep-08 13-Mar-09 3-Apr-09 21-Apr-09 30-Apr-09 1-Oct-09 1-Feb-10

Event Text (uncoded)

ILEOCOLICINTUSSCEPTION INTERCEPTION (INTESTINAL BLOCK) INTUSSUSCEPTION INTUSSUSPTION INTUSUSCCPTION INTUSSUSCEPTION INTUSSUSCEPTION , USG ABDOMEN - BOWEL WALL EDEMA SUGGESTIVE OF ?AUTOREDUCTION OF INTUSSUSCEPTION. 18-May-10 29-Oct-10 2-Nov-10 14-Mar-11 16-May-11 2-Jul-11 7-Jul-11 ILEOCAECAL- COLIC INTUSSUSN REQD RESECTN ANASTOMOSIS FOR GANGRENOUS BOWEL.

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.

OPERATED FOR REDUCTION OF INTUSSUCEPTION DIAGNOSED INTUSSUSCEPTION ON USG ABD . SURGICAL REDUCN DONE 31/2 MTH OLD FCH WAS ADMINISTERED RTX 1ST DOSE AT 11.15 AM ON 1ST JUL"11 . BABY died within 12 hrs of vaccination . 5 MONTH OLD BABY DEVELOPED INTUSSUSCEPTION 2 MONTHS AFTER THE 2ND DOSE OF ROTARIX VACCINE.

OCEANS Case ID

B0538669A B0565009A B0569117A B0570898A B0572643A B0595936A B0630353A B0653433A B0682689A B0682885A B0707294A B0719556A B0730358A B0732028A

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 2006

7 cases of intussusception have been reported 2. Data Lock Points: 12 January 2006 . 11 July 2006 13 cases of intussusception after vaccination have been reported 3. Data Lock Points: 12 July 2006 –11 January 2007 24 cases of intussusception were received 4. Data Lock Points: 12 January 2007 – 11 July 2007 97 cases

5. Data Lock Points: 12 July 2007 – 11 January 2008

98 cases

6. Data Lock Points: 12 January 2008 – 11 July 2008

85 cases of intussusception have been received.

of intussusception (IS) have been received during the period of this report.

of intussusception (IS) have been received during the period of this report.

7. Data Lock Points: 12 July 2008 – 11 Jan 2009

• 98 cases of intussusception (IS) have been received during the period of this report.

8. Data Lock Points: 12 Jan 2009 – 11 Jul 2009

• 46 cases of intussusception (IS) have been received during the period of this report.

9. Data Lock Points: 12 Jul 2009 – 11 Jan 2010

• • 21 cases of intussusception (IS) have been received during the period of this report.

10. Data Lock Points: 12 Jan 2010 – 11 Jul 2010

• 61 cases of intussusception (IS) have been received during the period of this report

11. Data Lock Points: 12 Jul 2010 – 11 Jul 2011

53 cases of intussusception (IS) have been received during the period of this report

Thanks you

• • •

Rotarix™ and Rotateq® active surveillance in Australia

Rotarix is a trademark of the GlaxoSmithKline group of companies RotaTeq is a registered trademark of Merck & Co., Inc.

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] 1–21 days RR 3.5 (95%CI: 0.7, 10.1) 1.5 (95%CI: 0.4, 3.9) 5.3 (95%CI: 1.1, 15.4) 3.5 (95%CI: 1.3, 7.6) Buttery et al. Vaccine 2011, doi: 10.1016/j.vaccine.2011.01.088 [in press] Global Expert Academy on Rotavirus ROT-2010-027 - 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™) Rotarix is a trademark of the GlaxoSmithKline group of companies RotaShield is a trademark of Wyeth 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) Global Expert Academy on Rotavirus ROT-2010-027 - 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

Dose

1 2

Risk period (days)

0–31 0–31

IS relative incidence

1.752

1.076

99% CI

0.997–3.080

0.618–1.873

P = 0.010

P = 0.734

 Clustering of IS cases within 7 days of vaccination observed post-Dose 1, but not post-Dose 2 Rotarix is a trademark of the GlaxoSmithKline group of companies 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) Global Expert Academy on Rotavirus ROT-2010-027 - 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, 2010 1  The corresponding label update is under review by the other Authorities Rotarix is a trademark of the GlaxoSmithKline group of companies 1.

http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM133539.pdf

[accessed Sept 29 th 2010] Global Expert Academy on Rotavirus ROT-2010-027 - Sponsored by GlaxoSmithKline Biologicals

Rotarix™ efficacy against severe RVGE (Rota-037, Africa)

• • • Rotarix is a trademark of the GlaxoSmithKline group of companies 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

*Rotarix™ N=2,974 n (%) Placebo N=1,443 n (%) VE % (95% CI) p value

Severe RVGE 56 (1.9) 70 (4.9)

61.2

(44.0–73.2) <0.001

*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 Global Expert Academy on Rotavirus ROT-2010-026 - Sponsored by GlaxoSmithKline Biologicals

Burden of RV potentially prevented in Africa (Rota-037)

Severe RVGE episodes prevented per 100 children per year – comparison with Latin America (and Finland) study (Rota-023) 4 2 0 14 12 10 8 6 5 episodes prevented 6.7

episodes prevented 4.2

episodes prevented Placebo Vaccine 1 episode prevented South Africa and Malawi combined Malawi South Africa Latin America 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 Global Expert Academy on Rotavirus ROT-2010-026 - Sponsored by GlaxoSmithKline Biologicals

Rotarix™ global efficacy against severe RVGE

Rotarix is a trademark of the GlaxoSmithKline group of companies Central and South America 11 countries severe RVGE 1,2 1st FU: 84.7% (71.7–92.4) 2nd year FU: 80.5% (71.3–87.1) OPV co-ad (six countries) severe RVGE 4 1st year FU: 81.6% (54.4–93.5) Europe Six countries severe RVGE 3 1st FU: 95.8% (89.6–98.7) 2nd FU: 90.4% (85.1–94.1) Africa Two countries severe RVGE 8 1st FU: 61.2% (44.0–73.2) Co-ad, co-administration; FU, follow-up References in speaker notes Global Expert Academy on Rotavirus South East Asia 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) ROT-2010-026 - Sponsored by GlaxoSmithKline Biologicals

Rotarix™ protects against a broad range of RV types: integrated analysis of randomised control trials

• Rotarix is a trademark of the GlaxoSmithKline group of companies Meta-analysis of five studies: Rota-004 (Finland), 006 (Brazil, Mexico, Venezuela), 007 (Singapore), 023 (Latin America – 11 countries), 036 (Europe – 6 countries) 100 90 80 70 60 50 40 30 20 10 0 82.6% 87.7% 84.9% 60.6% 81.0% 100 90 80 70 60 50 40 30 20 10 0 87.4% 90.2% 93.4% 83.8% 71.4% G1P[8] G3P[8] G4P[8] G9P[8] G2P[4] G1P[8] G3P[8] G4P[8] G9P[8] G2P[4]

Any RVGE Severe RVGE (≥11 Vesikari score)

CI, confidence intervals De Vos B et al. Pediat Infect Dis J 2009; 28: 261–6. Figures reproduced with permission from Lippincott Williams & Wilkins.

Global Expert Academy on Rotavirus ROT-2010-026 - Sponsored by GlaxoSmithKline Biologicals

Rotarix™ protects against a broad range of RV types

Rotarix is a trademark of the GlaxoSmithKline group of companies Source Ruiz-Palacios et al. 2006 1 Neuzil et al. 2009 2 Vesikari et al. 2007 3 Source Linhares et al. 2008 4 Latin America Africa Europe Latin America

G1

90.8

[70–98] 64.1

[30–82] 96.4

[86–100] 82.7

[64–93]

G2

43.8

[<0–88]

G3

**82.2

[70–90] Phua et al. 2009 5 Asia 100 [81–100] 100 [<0–100] 94.5

[65–100] Vesikari et al. 2007 3 Europe 96.4

[90–99] 85.5

[24–99] 93.7

[53–100] *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 Global Expert Academy on Rotavirus

G4

**82.2

[70–90] 95.4

[68–100]

G8 VE [95% CI] against severe RVGE 1-year follow-up

45.4

[<0–86] 79.2

[9–97] *86.9 [63–97] 83.8

[10–98] *86.9 [63–97] 64.4

[17–85] 74.7

[<0–100] 100 [45–100] 100 [65–100] -

VE [95% CI] against severe RVGE 2-year follow-up

-

G9

*86.9 [63–97] 94.7

[78–99] **82.2

[70–90] 91.7

[44–100] 85.0

[72–93]

G12

51.5

[<0–78] ROT-2010-026 - Sponsored by GlaxoSmithKline Biologicals