ROTARIX™ the human rotavirus vaccine: -is applied in a 2-dose schedule-

completes the course at the earliest possible age,

prevents morbidity and mortality from RV GE

regardless of the circulating strains

Dr. Bernd Benninghoff

GSK Vaccines, GML

Global Medical Affairs Director

0

20

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60

80

100

Severe RVGE: Vesikari score = ≥11; *follow-up over 2 years Severe RVGE: requiring hospitalization and / or rehydration therapy at medical facilities VE, vaccine efficacy

VE

agai

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sev

ere

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E (%

)

Asia1* Europe2 Latin America oral polio vaccine

co-admin3

Latin America5¶

Africa6 N=

5263 vaccine 5256 placebo

N= 2572 vaccine 1302 placebo N =

4211 vaccine 2099 placebo

N= 2974 vaccine 1443 placebo

1-2 year follow-up

N = 10,159 vaccine 10,010 placebo

Japan4*

N = 498 vaccine 250 placebo

1Phua K et al. Vaccine 2009;27:5936–41; 2Vesikari T et al. Lancet 2007;370:1757–63; 3Tregnaghi M et al. Ped Infect Dis J 2011;30:e103–8; 4Kawamura N et al. Vaccine 2011:29:6335–41; 5Linhares A et al. Lancet

2008:371:1181–9; 6Madhi S et al. N Engl J Med 2010;362:289–98

Global efficacy of HRV

Rotarix™ – product profile • Live-attenuated human virus, G1P[8] strain (RIX4414)1,2

• Launched in more than 130 countries, more than 130 mill of doses have

been administrated since 2004

• Oral vaccine: either lyophilized (1 mL), or liquid (1.5 mL)1

• Vaccine concentration: 106 median Cell Culture Infective Dose (CCID50)1

• Two doses:1

– First dose as early as 6 weeks of age

– Second dose completed by 24 weeks

(preferably before 16 weeks)

– Minimum interval between doses:

4 weeks

• Co-administration with other vaccines1–3

– Diphtheria-tetanus-whole cell pertussis (DTPw), diphtheria-tetanus-acellular

cell pertussis (DTPa), hepatitis B vaccine (HBV), Haemophilus influenzae type

B (Hib), inactivated polio vaccine (IPV), oral polio vaccine (OPV), meningitis C,

Streptococcus pneumoniae

• 3 year shelf life

– the vaccine is stable at high temperatures of 37°C for up to 7 days1 3 1. Rotarix™. Summary of Product Characteristics, 2012; 2. Dennehy PH et al. Pediatrics 2008; 122: e1062–6; 3. Steele AD et al. Vaccine 2008;

Sep 8 [Epub].

Key clinical features • Rotarix has demonstrated efficacy against several fully heterotypic strains,

providing evidence of broad protection against rotavirus currently

circulating. 1

• Rotarix has demonstrated sustained high levels of protection for 3 years,

with evidence of minimal waning immunity.2

• There is increasing evidence that widespread vaccination with Rotarix can

result in herd protection, thereby enhancing the benefits of vaccination

beyond the expected population based on trial data alone.3

• Rotarix vaccination has a substantial impact on all cause gastroenteritis,

reducing hospitalisation for gastroenteritis by 72% over a 2-year period in

a European study. This highlights the significance of rotavirus as a

causative agent.4

• Rates of nosocomial rotavirus infection have substantially decreased by

~67% and ~87% in Austria and urban Australia respectively after rotavirus

universal mass vaccination.5,6

1 Rotarix™. Summary of Product Characteristics, 2012; 2 Phua KB, et al. Rotavirus vaccine RIX4414 efficacy sustained during the third year of life.

Vaccine 2012;epub 3. Safadi MA,. Hospital-based surveillance to evaluate the impact of rotavirus vaccination in Sao Paulo, Brazil. The Pediatric

infectious disease journal 2010;29(11):1019-22. 4 O'Ryan M,. Rotarix(R): vaccine performance 6 years postlicensure. Expert review of vaccines

2011;10(12):1645-59. 5 Paulke-Korinek M,. UMV against rotavirus gastroenteritis: The Pediatric infectious disease journal 2010;29(4):319-23.

6. Macartney KK, et al.. J Paediatr Child Health 2011;47(5):266-70.

Both vaccines

USA,

Mexico.

Rotarix™ :

Canada (Ontario +

Quebec 11/2011)

Brazil,

El Salvador,

Panama,

Venezuela,

Ecuador,

Peru,

Colombia

Bolivia (GAVI)

Honduras (GAVI)

Paraguay (2010)

Guatemala

Dominican Rep.

RotaTeq ™ :

Nicaragua (GAVI)

Guyana (GAVI)

Cayman Islands

Australia,

both vaccines

Both vaccines

Belgium

Germany (5 Federal

States1)

Rotarix™ :

Luxemburg

Austria

Italy (Sicily)

Croatia (Risk patient2)

RotaTeq™:

Finland

Israel

Countries with national/regional RotarixTM immunization Countries with national/regional RotaTeq TM immunization

Countries without national RV immunization

ROTATEQTM

Iraq

Rotarix™ :

Bahrain

Qatar

Yemen (GAVI)

Saoudi Rotarix™:

Morocco

NorthSudan (GAVI)

South Africa

Ghana (GAVI)

Botswana

RotaTeq™:

Rwanda (GAVI)

Countries with rotavirus vaccination in childhood immunization calendar*

RotarixTM

Palau

Micronesia

Fiji

Philippines3

More specific information in notes below

*as of 18/07/2011

1. Saxony, Mecklenburg-vorpommen, Thuringia, Branbenbrug, Schleswig-Holstein

2. Pre-terms before 33wk of age, Children with congenital heart disorder , with congenital metabolic diseases , with liver and kidney diseases, with severe CNS

impairment

Coming soon: • Several GAVI-

eligible countries

Twelve HRV post-licensure observational studies

• Active surveillance in sentinel centres

• Belgium1, Australia2, Brazil3,4 South Africa10

• 35–93% reduction in RV GE-associated hospitalizations

• substantial decline in gastroenteritis associated with rotavirus infection

(i.e. 67%) among South African children aged 5 years10

• Passive surveillance in Australia5, Panama6, Mexico7, Brazil8

• 11–40% reduction in GE-associated hospitalizations

• Reduction in GE-associated deaths

• 22–33% reduction in diarrhea-related mortality3,8

1Zeller M et al. Vaccine 2010;28:7507–13; 2Macartney KK et al. J Paediatr Child Health 2011;47:266–70; 3Gurgel RG et al. Gastroenterology 2009;137:1970–5; 4Safadi MA et al. Pediatr Infect Dis J 2010;29:1019–22; 5Buttery JP et al. Pediatr Infect Dis J 2011;30:S25–29; 6Molto Y et al. Pediatr Infect Dis J 2011;30:S16–20; 7Quintanar-Solares M et al. Pediatr Infect Dis J 2011;30:11–15; 8do Carmo GM et al. PLoS Med 2011;8:e1001024; 9Lanzieri TM et al. Int J Inf Dis 2011;15:e206–10 10 SeheriVaccine 30S (2012) C14– C20 11 O’Ryan M et al. Expert Rev Vaccines 2011;10:1645–59 12 T.Braeckman BMJ 2012;345:

Six HRV post-licensure controlled effectiveness studies

• Significant protection against rotavirus-associated hospitalization was observed

in four of these studies ranging from 76 to 85% 11.

• The effectiveness study in Belgium has shown that two doses of Rotarix offer

vaccine effectiveness (overall), 91% (75% to 97%) 12

• RV vaccination reimbursed in Belgium since November 2006

• Using 1 September 2006 as the birth date to categorise

children with or without opportunity to receive RV vaccination,

data show a decline in the number of RV-positive samples

across successive birth cohorts

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600

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Adapted from Raes M et al. PIDJ 2011; 30: e120–5.

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ests

RV positive test after universal RV vaccination

in Belgium by birth cohorts (inpatient only)

Birth cohort 0 (° before Sep 06)

Birth cohort 1 (° Sep 07–Aug. 08)

Birth cohort 2 (° Sep 08–Aug 09*)

Birth cohort 3 (° Sep 09–May 10*) * end of observation period

RV=rotavirus

The value of Rotarix™

HumanRV 1

Two-dose schedule1

UNIQUE ATTRIBUTES

OF ROTARIX™

ADVANTAGES OF

TWO-DOSE ROTARIX™

Potential for greater

compliance3

HIGH VALUE POTENTIAL

OF ROTARIX™

Reduced cost of

implementing

a vaccination programme2

1. Rotarix™ Summary of Product Characteristics, 2008. 2. Weycker D JE, et al. Cost of routine immunization of young children against rotavirus infection with Rotarix versus RotaTeq. Vaccine

2009; 27: 4930-7. 3. Krishnarajah et al. Vaccine 2011

Full protection from a younger age Time, storage space and

cost savings

• Potential reduction of disease burden

• Potential cost of illness reduction

Full course completed

by 10 weeks of age1

convenient in two

doses

Fewer potential cases of

RV

Seropositivity rates at pre-dose-1 from 46,398 infants

analyzed from 16 GSK sponsored studies, of which

20,099 infants had received at least one dose of

placebo. R

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0

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10

15

20

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30

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6.9+

1.02

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0.69

12.2

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7

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2.37

8.6+

2.20

8.2+

1.80

9.3+

2.04 11

.4+1

.84

8.5+

1.78

Africa Asia LatinAmerica

Europe

8.6+

1.98

7.6+

1.75

North America

8.6+

1.31

Numbers on top of the bars indicate mean age with standard deviation at pre-dose-1 time point

The estimates for Vaccine Efficacy seem to be different in various regions of the world; probably due to the high level of exposure early during the first months in developing countries

Early protection in UMV is important to help reduce the number of infections

Htay Htay Han, PV Suryakiran, Serge Debrus, Bernd Benninghoff WSPID - November 18-22, 2009, Buenos Aires, Argentina.

Rotarix 2 dose schedule can complete the

course as early as possible

• To be optimally effective and cost-effective, a

vaccination schedule should aim to induce

immunity with the fewest number of doses

before a sizeable proportion of the target

population acquires natural infection. In

countries, where natural infection occurs

early, completion of the immunization

schedule early in infancy is desirable.

Conclusions

• Pre-licensure trials with HRV showed high efficacy rates against

clinically significant RVGE

• Post-licensure: HRV has had significant impact in reducing

severe RVGE, reduced the number of deaths due to RVGE and

demonstrate cost savings linked to the routine implementation of

rotavirus vaccination

• Rotarix is cost effective and reduces hospitalisations/mortality

and resource utilisation; in some countries Rotarix is cost-saving

from a societal perspective

• Real life data continues to confirm that Rotarix results in good

compliance and earlier completion with a two does schedule

• The main challenge is to increase RV vaccine use in National

Vaccine Programs, especially in less developed countries –

where early protection should be most impactful