Dr. Bernd Benninghoff GSK Vaccines, GML Global Medical Affairs Director

Transcription

1 ROTARIX the human rotavirus vaccine: -is applied in a 2-dose schedulecompletes 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

2 VE against severe RVGE (%) Global efficacy of HRV year follow-up Asia 1* N= Japan 4* N = Europe 2 N= Latin America 5 Latin America oral polio vaccine 5263 vaccine 498 vaccine 2572 vaccine co-admin placebo 250 placebo 1302 placebo N = N = 10,159 vaccine 4211 vaccine 10,010 placebo 2099 placebo Africa 6 N= 2974 vaccine 1443 placebo Severe RVGE: Vesikari score = 11; *follow-up over 2 years Severe RVGE: requiring hospitalization and / or rehydration therapy at medical facilities VE, vaccine efficacy 1 Phua K et al. Vaccine 2009;27: ; 2 Vesikari T et al. Lancet 2007;370: ; 3 Tregnaghi M et al. Ped Infect Dis J 2011;30:e103 8; 4 Kawamura N et al. Vaccine 2011:29: ; 5 Linhares A et al. Lancet 2008:371:1181 9; 6 Madhi S et al. N Engl J Med 2010;362:289 98

3 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: 10 6 median Cell Culture Infective Dose (CCID 50 ) 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 vaccines 1 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 days 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].

4 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): O'Ryan M,. Rotarix(R): vaccine performance 6 years postlicensure. Expert review of vaccines 2011;10(12): Paulke-Korinek M,. UMV against rotavirus gastroenteritis: The Pediatric infectious disease journal 2010;29(4): Macartney KK, et al.. J Paediatr Child Health 2011;47(5):

5 Countries with national/regional Rotarix TM immunization Countries without national RV immunization 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 Countries with rotavirus vaccination in childhood immunization calendar* More specific information in notes below Both vaccines Belgium Germany (5 Federal States 1 ) Rotarix : Luxemburg Austria Italy (Sicily) Croatia (Risk patient 2 ) RotaTeq : Finland Israel Rotarix : Morocco NorthSudan (GAVI) South Africa Ghana (GAVI) Botswana RotaTeq : Rwanda (GAVI) Countries with national/regional RotaTeq TM immunization ROTATEQ TM Iraq Rotarix : Bahrain Qatar Yemen (GAVI) Saoudi Australia, both vaccines Rotarix TM Palau Micronesia Fiji Philippines 3 *as of 18/07/ 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 GAVIeligible countries

6 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 Twelve HRV post-licensure observational studies Active surveillance in sentinel centres Belgium 1, Australia 2, Brazil 3,4 South Africa % reduction in RV GE-associated hospitalizations substantial decline in gastroenteritis associated with rotavirus infection (i.e. 67%) among South African children aged 5 years 10 Passive surveillance in Australia 5, Panama 6, Mexico 7, Brazil % reduction in GE-associated hospitalizations Reduction in GE-associated deaths 22 33% reduction in diarrhea-related mortality 3,8 1 Zeller M et al. Vaccine 2010;28: ; 2 Macartney KK et al. J Paediatr Child Health 2011;47:266 70; 3 Gurgel RG et al. Gastroenterology 2009;137:1970 5; 4 Safadi MA et al. Pediatr Infect Dis J 2010;29: ; 5 Buttery JP et al. Pediatr Infect Dis J 2011;30:S25 29; 6 Molto Y et al. Pediatr Infect Dis J 2011;30:S16 20; 7 Quintanar-Solares M et al. Pediatr Infect Dis J 2011;30:11 15; 8 do Carmo GM et al. PLoS Med 2011;8:e ; 9 Lanzieri TM et al. Int J Inf Dis 2011;15:e SeheriVaccine 30S (2012) C14 C20 11 O Ryan M et al. Expert Rev Vaccines 2011;10: T.Braeckman BMJ 2012;345:

7 Number of RV-positive tests RV positive test after universal RV vaccination in Belgium by birth cohorts (inpatient only) 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 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 0 Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May RV=rotavirus Adapted from Raes M et al. PIDJ 2011; 30: e120 5.

8 The value of Rotarix HumanRV 1 Two-dose schedule 1 UNIQUE ATTRIBUTES OF ROTARIX Full course completed by 10 weeks of age 1 convenient in two doses ADVANTAGES OF TWO-DOSE ROTARIX Full protection from a younger age Potential for greater compliance 3 Time, storage space and cost savings Fewer potential cases of RV HIGH VALUE POTENTIAL OF ROTARIX Potential reduction of disease burden Potential cost of illness reduction Reduced cost of implementing a vaccination programme 2 1. Rotarix Summary of Product Characteristics, Weycker D JE, et al. Cost of routine immunization of young children against rotavirus infection with Rotarix versus RotaTeq. Vaccine 2009; 27: Krishnarajah et al. Vaccine 2011

9 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. % seropostive (pre-dose-1 time point) Rota Rota Rota-037 Africa Rota Rota Rota-045 Asia Rota-028/029/030 Rota Rota Rota-033 Latin America Numbers on top of the bars indicate mean age with standard deviation at pre-dose-1 time point Rota Rota Rota Rota-036 Europe Rota Rota-005 North America 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.

10 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.

11 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