Rotarix

Beatrice De Vos, MD, BCPMDirector, Worldwide Medical Affairs

119

Rotavirus:a global

market for aglobal need

Rotarix

Rotarixhigh value potential

Rotarixproductprofile

120

Rotavirus: A Highly Contagious Virus Leading to Severe Dehydration in Children

• Transmission fecal-oral • Infectious for several days

• First infection is most severe Hospital

FamiliesDay care

Transmission

• Fever, watery diarrhea and vomiting à dehydration

Velazquez FR et al. N Engl. J Med, 1996;335(14):1022-1028

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Rotavirus: Leading Cause of Hospitalizationfor Diarrhea in Children Under 5

• Source of Winter Chaos in Hospitals • Cause of Prolonged Stay in Hospital

Community acquired RV hospitalizations - children < 5 y (Germany)

X 11

Noah, N. and Henderson, B.(2002). Surveillance of bacterial meningitis in Europe 1999/2000. European Bacterial Meningitis Surveillance Project. PHLS Communicable Disease Surveillance Centre.

Verstraeten T et al. Proc 23rd Ann Meeting Eur Soc Paediatric. Infect Dis (ESPID) May 18-21, 2005, Spain

0

2000

4000

6000

8000

10000

12000

Rotavirus Meningitis (any)

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Rotavirus: A Variety of Serotypes with Global Distribution

• Rotavirus comes in many serotypes, however, rotavirus diarrhea is most commonly associated with 4 key serotypes:

– G1P[8], G2P[4], G3P[8] and G4P[8]

Adapted from Parashar et al, Emerg Infect Dis 1998 4(4) 561–570; Gentsch et al, J Infect Dis 1996 174(1) S30–S36. Reproduced with permission from The University of Chicago Press.

53%

11%

5%

14%

3%

14%Global distribution of RV strains G1P[8]

G2P[4]

G3P[8]

G4P[8]

Mixed

Others: NT

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Rotavirus: A Quick-Changing Artist

• Prevalence of the RV serotypes changes yearly

• Newly emerging strain = G9

% UK rotavirus diarrhea caused by RV serotypes over time (1995-2003)

Itturiza-Gómara M et al. Journal of Clinical Microbiology 2000 38(12) 4394-4401

0

25

50

75

100

1995-96 1996-97 1997-98 2000-01 2001-02 2002-03

G1

G2

G3

G4

G9

Other

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Rotavirus Burden is Extensive

Each child will be infected at least once before his 5th birthday, wherever they live and whether they are rich or poor1

Each child will be infected at least once before his 5th birthday, wherever they live and whether they are rich or poor1

1 in 6 will require a physician visit11 in 6 will require a physician visit1

1 in 45 will require hospitalisation11 in 45 will require hospitalisation1

1 Parashar T et al. Emerg Infect Dis 2003 9(5) 565-5722 Verstraeten T et al. Proc 23rd Ann Meeting Eur Soc Paediatr. Infect Dis (ESPID) May 18-21, 2005, Spain

1 in 40,000

1 in 1,000

1 in 500

US1 Middle IncomeCountries Int'l1

Low IncomeCountries1,2

And significant mortality risk varies across the world1:And significant mortality risk varies across the world1:

Ris

k of

mor

taili

tyin

ch

ildre

n un

der

5

1 in 55,000

Europe1

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Lesson from Nature:

Two natural rotavirus infections confer ~ 100% protection against moderate/severe diarrhea and vomiting, regardless

of serotype

Velazquez et al, N Eng J Med 1996 335 1022–1028; Velazquez et al, J Infect Dis 2000 182 1602–1609;

RV Vaccine should mimic the immune response to a natural rotavirus infection in order to:

• Protect against moderate/severe disease

• Prevent hospitalization and death

• Reduce morbidity and socioeconomic burden

Goal of Rotavirus Vaccination

126

Rotavirus:a global

market for aglobal need

Rotarix

Rotarixhigh value potential

Rotarixproductprofile

127

Striking temporal association

Murphy et al, N Engl J Med 2001 344 564–72. Copyright © 200x [2001] Massachusetts Medical Society. (All rights reserved)

Rotavirus Vaccines: A Bit of History…. Rotashield

• Rhesus-based 4-valent vaccine by Wyeth• Licensed by FDA in August 1998 • Recommended for Universal Use by ACIP/AAP in 1998• Withdrawn in October 1999 due to link with Intussusception

(IS = bowel obstruction)

VaccinationFirst Dose

128

GSK’s Rotarix: based on an attenuated single human RV strain to mimic natural protection

- based on most prevalent circulating strain globally- present more relevant antigens- safe as no link between human rotavirus natural infection and IS

Two vaccines – Two different development strategies

Merck’s vaccine: based on an attenuated 5-valent animal (bovine) human reassortant RV strain

- combined with human proteins to increase breadth of protection

Rotavirus Vaccines:Newly Licensed or Late Stage RV vaccines

129

Rotarix: Outstanding Efficacy

*Statistically significant**Meta-analysis of studies 004-006-023G4: no data available

Any RV-GE*1

73%

G1*

92%

G9*

91%

G3*

88%

G2**

67%

All G-types2

severe RV-GE*85%

Hosp RV-GE2*

85%

EU studiesEU studies Latin-America studiesLatin-America studies

1 Vesikari T et al, Pediatr Infect Dis J 2004; 23(10):937-9432 Velazquez FR et al, Proc 23rd Annual Meet Soc Paediatr

Infect Dis (ESPID), 2005, abstr 5

130

• More than 100,000 doses of Rotarix administered

• No fever, diarrhea or vomiting increase vs placebo

Rotarix: Safe and Evidence of No Increased Intussusception Risk after Vaccination

Treatment Group

IS cases within 30-day

window

IS casesoutside 30-day

window

Total

Rotarixn ~ 31,000

6 3 9

Placebon ~ 31,000

7 9 16

O'RyanM et al Proc 44th ICAAC Washington 2004:14

131

Product Profiles: GSK’s Rotarix and Merck’s Bovine based vaccine candidate

Rotarix Merck

üü• Safety

Results show no increased risk for IS

protective

No data communicatedü üü

• ProtectionAny - Severe RV GE:Cross-protection: Oral Polio Virus co-admin:

protective

5• Manufacture

Number of strains 1

Bitter

2 doses, 1 ml 3 doses, 2 ml

Sweet

• ConvenienceNumber of doses, volume Taste

132

Rotavirus:a global

market for aglobal need

Rotarix

Rotarixhigh value potential

Rotarixproductprofile

133

Precedent For Medical Need and Market Potential

Before withdrawn, Rotashield was: Recommended by ACIP / AAP and was put on Vaccines For Children formulary

• On the market for 10 months • with roughly 1.1 million doses • administered to 600,000 infants • out of 4m birth cohort

• Priced at $38 per dose, 3 per course ($114)

Source: http://www.cdc.gov/nis/pdfs/miscellaneous/khare2003c.pdf

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Rotavirus Market Potential 2010 by Region

Estimated Global Market 2010: £1.0-1.3 billion

GAVI15%

US25%

International

40%

Europe20%

135

Rotarix: Dynamic Market Building

US - Europe - International

Low Income Countries

• Market build-up (disease awareness)• Product differentiation

• Manufacture Capacity build-up• Partnership with Public Sector

WHO Recommendation WHO Recommendation

ACIP - Country Recommendation ACIP - Country

Recommendation

One Objective: Universal Mass VaccinationOne Objective: Universal Mass Vaccination

136

20062005

LaunchMexico

Q2 06

Rotarix: Key Milestones

Jan Q3-Q4

2007

4Q07

20082004

FileEU

LaunchLatin-America

LaunchEU

Dec Q1 06

• Ongoing FDA Discussion

LaunchAsia Pacific

137

Rotarix: Conclusion

ü High medical need demonstrated

ü Rotarix: Broad protection

ü Rotarix: Early protection with 2 doses

ü Rotarix: Excellent safety profile;No increased risk for IS