Rotarix : Global Efficacy against Severe RV GE due to G1 and non-g1 (G2, G3, G4, G9) RV Types

Transcription

1 Rotarix : Global Efficacy against Severe RV GE due to G1 and non-g1 (G2, G3, G4, G9) RV Types 8 th International Rotavirus Symposium Istanbul, 3 rd June 2008 Dr. Norman Begg, Vice President, Clinical Development GlaxoSmithKline Biologicals, Rixensart, Belgium

2 Challenges for the development of a global Rotavirus vaccine No increased risk of IS compared to placebo Broad protection against known and emerging strains Efficacy from an early age and peak incidence period No interference with co-administered antigens Ease of inclusion in immunisation schedules Efficacy in developing and developed countries

3 Percent Efficacy Rational for Vaccination with Human RV Strain Natural RV infection attenuates severity of subsequent infections, regardless of serotype One Previous RV infection moderate to severe diarrhea mild diarrhea asymptomatic infection 62 Two Previous RV infections 1 Velazquez et al, N Eng J Med ; 2 Bernstein DI, et al. JID. 1991; 164(2); ; 3 Velazquez et al, J Infect Dis

4 Human RV Vaccine - Rotarix Lyopholized vaccine + liquid diluent (CaCO 3 ) 1 ml per dose Each dose: 10 6 CCID 50 of live, attenuated HRV strain G1 P(8) Orally administered 2 doses 1 st dose beginning at 6 weeks of age 2 nd dose at 4 weeks after first dose; completed by 24 weeks of age GlaxoSmithKline Biologicals, Rotarix TM Summary of Product Characteristics (Dec. 2007)

5 Pivotal phase III studies in Latin America and Europe Ruiz-Palacios et al. for the Human Rotavirus Vaccine Study Group. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med 2006; 354: Vesikari et al. Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study. Lancet 2007; 370:

6 Challenges for the development of a global Rotavirus vaccine No increased risk of IS compared to placebo Broad protection against known and emerging strains Efficacy from an early age and peak incidence period No interference with co-administered antigens Ease of inclusion in immunisation schedules Efficacy in developing and developed countries

7 No increased risk of Intussusception Vaccine group Placebo group Safety cohort N=31,673 Safety cohort N=31,552 Cases of IS 0 31 days days Relative Risk = 0.85 (0.30 ; 2.42)* 9 16 Relative Risk = 0.56 (0.25 ; 1.24)* No increased risk for IS compared to placebo Ruiz-Palacios G. et al. N. Engl. J. Med. 2006; 354: ; Macias M. et al., abstract, ICAAC, 2005, Washington, USA (poster) *95% CI

8 Challenges for the development of a global Rotavirus vaccine No increased risk of IS compared to placebo Broad protection against known and emerging strains Efficacy from an early age and peak incidence period No interference with co-administered antigens Ease of inclusion in immunisation schedules Efficacy in developing and developed countries

9 Latin America: Type-specific Efficacy for Severe Rotavirus GE From 2 weeks post-dose 2 until 24 months of age (ATP cohort) Vaccine efficacy (%) * Not statistically significant G1P[8] G2P[4] G3P[8] G4P[8] G9P[8] Low Number of G2P[4] due to low circulation of strain type Linhares, A.C., et al. Lancet 2008 Apr 5;371(9619): % [65;92] 79% [25;96] 39%* [<0;84] 62% [4;87] 87% [73;94]

10 Europe: Type-specific Efficacy for Severe Rotavirus GE From 2 weeks post-dose 2 until end of the 2 nd RV season (ATP cohort) Vaccine efficacy (%) % [90;99] 86% [24;99] 94% [53;100] 95% [68;100] 85% [72;93] G1P[8] G2P[4] G3P[8] G4P[8] G9P[8] Vesikari T, et al. Lancet 2007 Nov 24;370(9601):

11 Challenges for the development of a global Rotavirus vaccine No increased risk of IS compared to placebo Broad protection against known and emerging strains Efficacy from an early age and peak incidence period No interference with co-administered antigens Ease of inclusion in immunisation schedules Efficacy in developing and developed countries

12 Latin America: Efficacy over peak incidence (2 years) From 2 weeks post-dose 2 until 12 months of age From 2 weeks post-dose 2 until 24 months of age Vaccine efficacy (%) % [71;93] 81% [71;87] Severe RV GE Vesikari 85% [70;94] RV GE hosp. 83% [73;90] Severe RV GE Vesikari RV GE Hospitalization 40% [29;53] 39% [29;48] All causes Severe GE All-cause Severe GE Linhares AC, et al. Lancet 2008 Apr 5;371(9619):1181-9

13 Europe: Efficacy lasting 2 seasons From 2 weeks post-dose 2 until end of the 1st RV season (ATP cohort) From 2 weeks post-dose 2 until end of the 2nd RV season (ATP cohort) Vaccine efficacy (%) % [80;92] 79% [73;84] 96% [90;99] 90% [85;94] 100% 96% [82;100] [84;100] 92% [84;96] 84% [77;89] Any RV GE Severe RV GE RV GE Hosp Medicallyattended RV GE Vesikari T, et al. Lancet 2007 Nov 24;370(9601): % [46;89] 72% [53;83] All-cause GE Hosp

14 Europe: Efficacy after one dose From Dose 1 up to before Dose 2 (Total Vaccinated Cohort) Vaccine efficiacy (%) % [9;100] Any RV GE 100% [-23;100] Severe RV GE Vesikari T, et al. Lancet 2007 Nov 24;370(9601): ; GlaxoSmithKline Biologicals, Rotarix Summary of Product Characteristics (Dec 2007) According to Rotarix Summary of Product characteristics 2 doses are indicated.

15 Challenges for the development of a global Rotavirus vaccine No increased risk of IS compared to placebo Broad protection against known and emerging strains Efficacy from an early age and peak incidence period No interference with co-administered antigens Ease of inclusion in immunisation schedules Efficacy in developing and developed countries

16 Co-administration with other vaccines DTPw, DTPa, HBV, Hib, IPV, OPV, Men C, PCV-7 High Rotarix immune responses maintained No impairment of immune responses to any co-administered vaccine antigens Vesikari et al. PIDJ 2004,23: Salinas B et al. PIDJ, /9: Phua K et al. JID, 2005;192(suppl 1): S6-S16 Ruiz-Palacios G. et al. N. Engl. J. Med. 2006; 354: Tejedor JC et al. ESPID, Basel, Switzerland May 3 5, 2006, Abstract 456, Schuster VT et al. ESPID, Basel, Switzerland May 3 5, 2006, Abstract 461

17 Latin America (Rota 024): Co-administration of Rotarix with Oral Polio Vaccine Infants of 6-12 weeks % [54;93] 88% [64;97] Co-administration: OPV + 2 doses RIX4414 or Placebo (n=4376) (n=2192) Vaccine efficacy (%) Efficacy follow-up: 7.4m 10 0 Severe RV GE RV GE Hospitalization No impact on the efficacy of Rotarix In line with the high efficacy against severe RVGE of 85% demonstrated in the Latin American study with staggered OPV co-administration Tregnaghi, M. et al., Abstract, 13th ICID Kuala Lumpur, Malaysia- June 19-22,

18 Challenges for the development of a global Rotavirus vaccine No increased risk of IS compared to placebo Broad protection against known and emerging strains Efficacy from an early age and peak incidence period No interference with co-administered antigens Ease of inclusion in immunisation schedules Efficacy in developing and developed countries

19 Ease of inclusion in immunisation schedules Oral presentation 2 doses Flexible schedule starting from 6 weeks of age No interference with currently co-administered vaccines Rotarix can be flexibly integrated into a variety childhood immunisation schedules: 6,10 weeks; 6,14 weeks; 10,14 weeks; 2, 3 months; 2, 4 months; 3, 4 months or 3, 5 months of age Vesikari et al. PIDJ 2004,23: Salinas B et al. PIDJ, /9: Phua K et al. JID, 2005;192(suppl 1): S6-S16 Ruiz-Palacios G. et al. N. Engl. J. Med. 2006; 354: Tejedor JC et al. ESPID, Basel, Switzerland May 3 5, 2006, Abstract 456, Schuster VT et al. ESPID, Basel, Switzerland May 3 5, 2006, Abstract 461

20 Challenges for the development of a global Rotavirus vaccine No increased risk of IS compared to placebo Broad protection against known and emerging strains Efficacy from an early age and peak incidence period No interference with co-administered antigens Ease of inclusion in immunisation schedules Efficacy in developing and developed countries

21 Variance in serotype distribution G4P[8] 3.4% G9P[8] 17.2% G3P[8] 12.1% GXP[6] 1.7% Unknown 3.4% Latin America G1P[8] 51.7% 1 st Year Europe G9P[8] 33.9% G1P[8]+G4P[8] 0.8% G1P[8] 41.5% G2P[4] 12.1% G4P[8] 12.7% G3P[8] 5.1% G2P[4] 5.9% G9P[8] 54.4% G3P[6] 1.0% G1P[8] 24.3% G4P[8] 15.6% G2P[4] 1.0% G3P[8] 5.8% 2 nd Year Mixed 2.3% G12P[8] 1.2% G9P[8] 39.2% G4P[8] 4.7% Linhares AC, et al. Lancet 2008 Apr 5;371(9619): ; Vesikari T, et al. Lancet 2007 Nov 24;370(9601): Unknown 4.1% G3P[8] 4.1% G1P[8] 31.6% G2P[4] 12.9%

22 Efficacy in all Regions Rota-023 (11 countries) Severe RV GE 1 year 85% (71-93) 2 years 81% (71-87) Hospitalization for RV GE 1 year 85% (70-94) 2 years 83% (73-90) Linhares AC, et al. Lancet 2008 Apr 5;371(9619): Rota-036 (6 countries) Severe RV GE1 season 96% (90-99) 2 seasons 90% (85-94) Hospitalization for RV GE 1 season 100% (82-100) 2 seasons 96.0% (84-100) Any RV GE 1 season 87% (80-92) 2 seasons 79% (73-84) Vesikari T, et al. Lancet 2007 Nov 24;370(9601): Rota-024 OPV co-ad (6 countries) Severe RV GE 1st year 82% (54-93) Hospitalization for RV GE 1st year 88% (64-97) Lopez, P. et al., Abstract, 13th ICID Kuala Lumpur, Malaysia- June 19-22, Rota-028/029/030 (3 countries) Severe RV GE 1 year 100% (72-100) 2 years 96% (86-100) Hospitalization for RV GE 1 year 100% (67-100) 2 years 94% (81-99) Phua, K.B. et al., Abstract, 13th ICID Kuala Lumpur, Malaysia- June 19-22, Rota-037 Interim analysis to be presented at 8 th International RV symposium Madhi, S., Oral presentation, 8th international Rotavirus Symposium, Istambul, Turkey, June 3-4,

23 Summary: Rotarix No increased risk of IS compared to placebo Broad protection against known and emerging strains Efficacy from an early age, lasting 2 years No interference with co-administered antigens Ease of inclusion in immunisation schedules Efficacy in developing and developed countries