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

Rotarix: PMS

Dr. Shailesh MEHTA

GSKIAPCOI meeting Mumbai, 24th Dec 2011

Not a single case of Intussusception was reported in this study

PSUR Data of RotarixIndia

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 )

India

Sr No. Loc Ref No Age ( Months ) GenderDate Received

by GSK Event Text (uncoded) OCEANS Case ID

1 IN/2008/00131 5 Male 18-Sep-08 ILEOCOLICINTUSSCEPTION B0538669A

2 IN/2009/00027 N/A N/A 13-Mar-09 INTERCEPTION (INTESTINAL BLOCK) B0565009A

3 IN/2009/00038 4 Male 3-Apr-09 INTUSSUSCEPTION B0569117A

4 IN/2009/00055 5 Male 21-Apr-09 INTUSSUSPTION B0570898A

5 IN/2009/00058 7 Male 30-Apr-09 INTUSUSCCPTION B0572643A

6 IN/2009/00123 7 Male 1-Oct-09 INTUSSUSCEPTION B0595936A7 IN/2010/00011 3 Female 1-Feb-10 INTUSSUSCEPTION B0630353A

8 IN/2010/00041 5 Male 18-May-10

, USG ABDOMEN - BOWEL WALL EDEMA SUGGESTIVE OF ?AUTOREDUCTION OF

INTUSSUSCEPTION. B0653433A

9 IN/2010/00194 4 Male 29-Oct-10ILEOCAECAL- COLIC INTUSSUSN REQD RESECTN

ANASTOMOSIS FOR GANGRENOUS BOWEL. B0682689A

10 IN/2010/00196 7 Male 2-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. B0682885A

11 IN/2011/00083 4 Male 14-Mar-11 OPERATED FOR REDUCTION OF

INTUSSUCEPTION B0707294A

12 IN/2011/00136 7 Male 16-May-11 DIAGNOSED INTUSSUSCEPTION ON USG ABD .

SURGICAL REDUCN DONE B0719556A

13 IN/2011/00168 3 Female 2-Jul-11

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 . B0730358A

14 IN/2011/00170 5 Female 7-Jul-11

5 MONTH OLD BABY DEVELOPED INTUSSUSCEPTION 2 MONTHS AFTER THE 2ND

DOSE OF ROTARIX VACCINE. 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 reported2. Data Lock Points: 12 January 2006 . 11 July 2006• 13 cases of intussusception after vaccination have been reported3. Data Lock Points: 12 July 2006 –11 January 2007• 24 cases of intussusception were received4. Data Lock Points: 12 January 2007 – 11 July 2007• 97 cases of intussusception have been received.5. Data Lock Points: 12 July 2007 – 11 January 2008• 98 cases of intussusception (IS) have been received during the period of this report.6. Data Lock Points: 12 January 2008 – 11 July 2008• 85 cases 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 report11. 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

Global Expert Academy on Rotavirus ROT-2010-027 - 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

onlyIS 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 RR 1.5 (95%CI: 0.4, 3.9) 3.5 (95%CI: 1.3, 7.6)

Buttery et al. Vaccine 2011, doi: 10.1016/j.vaccine.2011.01.088 [in press]

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


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 2nd Excellence in Paediatrics conference, 2–4 Dec 2010, London, UK)

Rotarix is a trademark of the GlaxoSmithKline group of companiesRotaShield is a trademark of Wyeth


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 incidence 99% CI

1 0–31 1.752 0.997–3.080 P = 0.010

2 0–31 1.076 0.618–1.873 P = 0.734

Velazquez et al. Acta Pædiatrica 2010: 99(Suppl. 462): 47–120, PP106 (special issue: Abstracts from the 2nd Excellence in Paediatrics conference, 2–4 Dec 2010, London, UK)

Rotarix is a trademark of the GlaxoSmithKline group of companies


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, 20101

The corresponding label update is under review by the other Authorities

1.http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM133539.pdf [accessed Sept 29th 2010]


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


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

*Rotarix™ N=2,974 n (%)

PlaceboN=1,443n (%)

VE% (95% CI) p value

Severe RVGE 56 (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 cohortN = number of subjects included in each group; n = number of subjects reporting at least one event in each groupn/N (%) = percentage of subjects reporting at least one event; VE (%) = vaccine efficacy (conditional method); CI = confidence intervalsSeverity 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



0

2

4

6

8

10

12

14

South Africa and Malawi combined

Malawi South Africa Latin America

1episode

prevented

4.2episodes

prevented

6.7episodes

prevented

5episodes

prevented

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)

Seve

re R

VGE

epis

odes

per

100

in

fant

-yea

rs

PlaceboVaccine


OPV co-ad (six countries) severe RVGE4 1st year FU: 81.6% (54.4–93.5)

Three countriessevere RVGE5–7

1st FU: 100% (72.2–100)2nd FU: 96.1% (85.1–99.5)3rd FU: 100% (67.5–100.0)

Two countriessevere RVGE8

1st FU: 61.2% (44.0–73.2)

Six countriessevere RVGE3

1st FU: 95.8% (89.6–98.7)2nd FU: 90.4% (85.1–94.1)

11 countriessevere RVGE1,2

1st FU: 84.7% (71.7–92.4)2nd year FU: 80.5% (71.3–87.1)

Rotarix™ global efficacy against severe RVGE

Central andSouth America

Europe

South East Asia

Africa

References in speaker notesCo-ad, co-administration; FU, follow-up



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

Any RVGE Severe RVGE (≥11 Vesikari score)

Vacc

ine

effica

cy (%

, 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)

0102030405060708090

100

G1P[8] G3P[8] G4P[8] G9P[8] G2P[4]0

102030405060708090

100

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%



G1 G2 G3 G4 G8 G9 G12Source VE [95% CI] against severe RVGE 1-year follow-up

Ruiz-Palacios et al. 20061

LatinAmerica

90.8[70–98]

45.4[<0–86]

*86.9 [63–97]

*86.9 [63–97] - *86.9

[63–97] -

Neuzil et al. 20092 Africa 64.1

[30–82]79.2

[9–97]83.8

[10–98] - 64.4[17–85] - 51.5

[<0–78]

Vesikari et al. 20073 Europe 96.4

[86–100]74.7

[<0–100]100

[45–100]100

[65–100] - 94.7[78–99] -

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

Linhares et al. 20084

LatinAmerica

82.7[64–93]

43.8[<0–88]

**82.2[70–90]

**82.2[70–90] - **82.2

[70–90] -

Phua et al. 20095 Asia 100

[81–100]100

[<0–100]94.5

[65–100] - - 91.7[44–100] -

Vesikari et al. 20073 Europe 96.4

[90–99]85.5

[24–99]93.7

[53–100]95.4

[68–100] - 85.0[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: PMS Dr. Shailesh MEHTA GSK IAPCOI meeting Mumbai, 24 th Dec 2011.

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