Dr. Gaurav Gupta RV 5 Patiala CME 18 feb 2018

Comparing the 4 available Rotavirus vaccines in the Indian context, Rotateq (RV5), Rotavac/ Rotasure (116E), Rotarix (RV1), and Rotasiil (BRV-PV), with special reference to Rotateq.

1. Rotavirus Vaccines: What’s New? RV5/116E/RV1/BRV-PV Dr. Gaurav Gupta, Charak Clinics, Mohali

2. Conflict of Interest

3. Scope Indian RV seroprevalence Indian data of vaccines Comparing RV vaccines Strengths of RV5

4. Rotavirus Serotypes Changing Rotavirus serotype patterns.

5. RV Serotypes change as per time, region and setting Natural Infection Study: Gladstone et al 1 (2002-2006) Indian Rotavirus Strain Surveillance Network 2 (2005-2009) RVGE Outpatient Burden study 3 (2011-2012) * All values expressed as % Gladstone B P et al. N Engl J Med 2011;365 (4):337-46. 2. Kang G et al. Vaccine 31 (2013) 2879-2883. 3. Gajanan S. Namjoshi et al. Rotavirus gastroenteritis among children less than 5 years of age in private outpatient setting in urban India. Vaccines 32S (2014) A36-A44. G1P(8), 15.9 G2P(4), 13.6 G10P(11), 8.7 Others, 61.8 G1, 25 G2, 21 G9, 13 Others, 41 G1P(8), 32.1 G2P(4), 27.5 G2P(6), 7.33 Others, 33.1

6. Rotavirus Serotype distribution in India – IRSN (2012-2014) 1 Major genotypes: G1P[8] (62.7%), G2P[4] (7.6%), G9P[4] (4.2%), G12P[6] (3.7%). Sample size: N = 10,207. RV positive = 4042 (39.6%) 1. CP Girish Kumar et al. Rotavirus genotypes in India. Data from Indian Rotavirus Strain Surveillance Network (2012-2014). Poster presented at ds RNA conference in Oct 2015. (P1-40).

7. Rotavirus Vaccines in India: RV5/RV1/116E/BRV-PV

8. Rotavirus Vaccines in India Vaccine Valency Rotavirus strains Country of Manufacture No. of doses Dosing schedule Regulatory approval RotaTeq Pentavalent vaccine G1-G4,P8 Pennsylvania, USA 3 6, 10, 14 weeks Yes 116E Monovalent vaccine G9P11 India 3 6, 10, 14 weeks Yes BRV-PV Pentavalent vaccine G1-G4, G9 India 3 6, 10, 14 weeks Yes 3 Dose Rotavirus Vaccines: 2 Dose Rotavirus Vaccines: Company Valency Rotavirus strains Country No. of doses Dosing schedule Regulatory approval RV1 Monovalentvaccine G1 Belgium,UK 2 10, 14 weeks Yes

9. Rotavirus Vaccines: RV5/RV1/116E/BRV-PV Indian Immunogenicity Data

10. Rotavirus Vaccines: Indian Immunogenicity Data* (*Not head to Head comparisons) Vaccine Design Schedule Results RV1 2 (n = 363) V-182/P-181 MONOVALENT VACCINE Immunogenicity & Safety Routine pediatric vaccines including OPV restricted to 14 days prior to each dose of RV1. 56 out of 182 infants (31%) in the vaccine group received OPV through the Pulse Polio Program within 14 days of vaccine. 2 dose schedule. Starting at 8 - 10 weeks. 2 nd dose 1 month post dose 1. Overall seroconversion * – 58.3% post dose 2. * Seropositivity defined as anti-rotavirus IgA concentration ≥ 20 U/ml. Lokeshwar et al. Immunogenicity and safety of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine (PRV) in Indian infants. Human Vaccines & Immunotherapeutics 9:1, 178–182; January 2013; c 2013 . Narang et al. Immunogenicity, reactogenicity and safety of human rotavirus vaccine (RIX4414 ) in Indian infants. Human Vaccines 5:6, 414-419; June 2009. Vipin Vashistha et al. Indian Academy of Pediatrics (IAP) Recommended Immunization Schedule for Children Aged 0 through 18 years – India, 2016 and Updates on Immunization. Indian Pediatrics. Aug 26 2016 [E-pub. Ahead of print]. P. 35. Bhandari N et al. Efficacy of a Monovalent Human-Bovine (116E) Rotavirus Vaccine in Indian Infants: A Randomized Double Blind Placebo Controlled Trial. Lancet. 2014; 383 (9935): 2136–43. Vaccine Design Schedule Results RV5 1 (n = 110) V-110 PENTAVALENT VACCINE (MERCK) Immunogenicity & Safety With concomitant administration of OPV (no restrictions on additional doses that may have been administered during the Pulse Polio Program) . No restrictions on breast feeding & other routine pediatric vaccines . 3 dose schedule. Starting at 6 weeks Overall seroconversion * - 83% post dose 3. G1 - 77.3%,G2 - 71.4% G3 - 55.6%,G4 - 93.3%,P1 - 90.0% * Seropositivity defined as anti-rotavirus IgA concentration ≥ 20 IU/ml. As per IAP 2016 recommendations, RV1 administered at 6 & 10 weeks is less immunogenic than RV1 given at 10 & 14 weeks 3 . Hence, IAP-ACVIP recommends RV1 at 10 & 14 weeks in order to achieve a better immune response 3 . Vaccine Design Schedule Results 116 E 4 ( Phase 3 trial) (n = 6799) V-4532/P- 2267 MONOVALENT VACCINE Efficacy, Immunogenicity & Safety. With Concomitant OPV, DTPw , Hib , Hep B . No restriction on breast feeding. Storage of vaccine (-20 degrees C ) & administration of citrate bicarbonate buffer 5-10 mins prior to vaccine. 3 dose schedule ( 1x10 5 FFU) . 6-10-14 weeks. Overall seroconversion * - 39.9% post dose 3. * Seroconversion defined as a 4-fold rise in titre from paired serum samples.

11. Rotavirus Vaccines: Indian Immunogenicity Data (Contd.): Pentavalent RV Vaccines ( Not head to head comparison trials) Lokeshwar et al. Immunogenicity and safety of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine (PRV) in Indian infants. Human Vaccines & Immunotherapeutics 9:1, 178–182; January 2013; c 2013 . Prasad Kulkarni et al. A randomized Phase III clinical trial to assess the efficacy of a bovine human reassortant pentavalent rotavirus vaccine in Indian infants. Vaccine (2017). https:// doi.org/10.1016/j.vaccine.2017.09.014. Vaccine Design Schedule Results RV5 1 (n = 110) V-110 PENTAVALENT VACCINE (MERCK) Immunogenicity & Safety With concomitant administration of OPV (no restrictions on additional doses that may have been administered during the Pulse Polio Program) . No restrictions on breast feeding & other routine pediatric vaccines . 3 dose schedule. Starting at 6 weeks Overall seroconversion * - 83% post dose 3. G1 - 77.3%,G2 - 71.4% G3 - 55.6%,G4 - 93.3%,P1 - 90.0% * Seropositivity defined as anti-rotavirus IgA concentration ≥ 20 IU/ml. Vaccine Design Schedule Results BRV-PV 2 (n = 219) V-116/P-103 PENTAVALENT VACCINE Efficacy, Safety & Immunogenicity & With concomitant administration of routine DTP-HB-Hib & OPV. No restrictions on breast feeding. 3 dose schedule. 6-10-14 weeks schedule. Overall seroconversion * - 33.6% post dose 3. * Seroresponse defined as ≥ 3 fold rise of anti-rotavirus IgA at Day 28 (+/- 7 Days) post-dose 3 when compared to baseline titres.

12. Rotavirus Efficacy and Safety Trial (REST) 1 Multicentre, in 11 countries on 3 continents (Europe, US, Latin America/Caribbean), from 2001 to 2004 Randomised , double-blind controlled, RotaTeq vs placebo 70,301 infants enrolled/68,038 received at least 1 dose of RotaTeq or placebo Age at enrollment: children 6 to 12 weeks Oral, 3-dose regimen, every 4–10 weeks Vesikari T, et al. N Engl J Med. 2006;354:23 – 33.

13. RotaTeq ® Proven Efficacy & Effectiveness Across Serotypes Vesikari T et al. Safety and Efficacy of a Pentavalent Human– Bovine (WC3) Reassortant Rotavirus VaccineN Engl J Med. 2006;354:23–33. Payne DC et al. Clin Infect Dis. 2013;57:13–20 Rest trial: Efficacy of RotaTeq on reduction of hospitalizations and emergency visits due to different serotypes (N=68,038: RotaTeq=34,035; placebo=34,003) 1 G1 G2 G3 G4 G9 95% 88% 93% 89% 100% (92-97) (0<99) NS (49-99) (52-98) (67-100) Effectiveness of RotaTeq by Genotype Among Children <5 Years of Age: New Vaccine Surveillance Network, US : 2010-2011 2 89% 87% 87% 83% G1P[8] G2P[4] G3P[8] G12P[8] Vaccine Effectiveness (%) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 0% 20% 40% 60% 80% 100%

14. Rotavirus Vaccine 116E

15. 116E Vaccine: Indian Immunogenicity Data Vaccine Setting Results 116 E 1 n= 1 X 10 4 FFU* 93(V) & 94 (P) 1 X 10 5 FFU* 92(V) & 90 (P) Phase 1b/ IIa : Safety and Immunogenicity, Dose Escalation study (3 dose schedule) Vaccine or placebo received at 8-12-16 weeks. Limitations: Risk of intussusception would become evident only during larger trials or PM surveillance. No concomitant administration of other childhood vaccines, including OPV. Breast feeding was restricted 30 mins prior to & post dosing. Stringent exclusion criteria. Storage of vaccine (-70 degrees C) & administration of citrate bicarbonate buffer prior to vaccine. Seroconversion 2 doses (% of infants with >=4 fold increase in IgA titres ) 3 doses (% of infants with >=4 fold increase in IgA titres ) 1 X 10 4 FFU* 116E 62.9% 62.1% 1 X 10 5 FFU* 116E *FFU=Focus forming Units. 67.7% 89.7% Safety No significant difference in clinical adverse events or lab toxicity between vaccine & placebo recipients 116 E 2 n= 4532(V) & 2267(P) 116 E 3 n= 4532(V) & 2267(P) Phase III study: Efficacy (3 dose schedule/1x10 5 FFU) Vaccine or placebo received at 6-10-14 weeks. Concomitant OPV, DTPw , Hib , Hep B. Cases of intussusception: 6/4532 (V) & 2/2267 (P) A thorough evaluation of risk of intussusception will await phase IV surveillance studies. Extension of Phase III study: Efficacy & Additional Safety upto 2 years of age. 39.9% Seroconversion in the vaccine & 18.4% in the placebo groups. Reasons cited for decreased immunogenicity: Study cohort healthier. No concomitant administration of OPV. Age of 1st dose earlier (6 vs 8 wks)-Possible interference by maternal anti RV IgG . Possible Breast feeding interference with “TAKE” of RV vaccine (controlled in 1b/ IIa ). Variability in Anti RV IgA response in different populations Bhandari N et al. A Dose-Escalation Safety and Immunogenicity Study of Live Attenuated Oral Rotavirus Vaccine 116E in Infants: A Randomized, Double-Blind, Placebo-Controlled Trial. The Journal of Infectious Diseases 2009; 200:421–9. Bhandari N et al. Efficacy of a Monovalent Human-Bovine (116E) Rotavirus Vaccine in Indian Infants: A Randomized Double Blind Placebo Controlled Trial. Lancet. 2014; 383 (9935): 2136–43. Bhandari N et al. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life . Vaccines 32S (2014) A110-A116.

16. First 1 and Second 2 Year Safety data – 116E 1.Bhandari N et al. Efficacy of a Monovalent Human-Bovine (116E) Rotavirus Vaccine in Indian Infants: A Randomized Double Blind Placebo Controlled Trial. Lancet. 2014; 383 (9935): 2136–43. 2. Bhandari N et al. Efficacy of a monovalent human-bovine (116E) rotavirus vaccinei n Indian children in the second year of life . Vaccines 32S (2014) A110-A116. Year Adverse Events Intussusception Remarks 1 st year Safety data 1 20.3% (V) n=925 22% (P) n=499 6/4532 (V) 2/2267 (P * A thorough evaluation of risk of intussusception will await phase IV surveillance studies. 2 nd year Safety data 2 20.9% (V) n=947 22.7% (P) n=515 8/4532 (V) 3/2267 (P) None occurred within 30 days of a vaccine dose and all were reported only after the third dose. The intussuception events following the third dose occurred between 112 and 587 days post vaccination in the vaccine group and between 36 and 605 days in the placebo group. 20 cases of G9P[11] GE seen after dose 1 & 2 cases post dose 2 of II6E RV vaccine . All cases were mild or moderate by VS 1

17. Rotavirus Vaccine BRV-PV

18. Formulations : BRV-PV & RotaTeq BRV-PV RotaTeq Lyophilized. Reconstitution required. Ready to use liquid formulation in a l atex – free dosing tube stable at 2-8 degrees 1 1. RotaTeq PI. MSDIN 11/16.

19. BRV-PV Thermostability Facts: (Data from Naik et al 2017 1 ) V accine is stable for 1 ( 2017 paper) < 25 C for 36 months. 18 months at 37◦ C, and 40◦C, 55+/- 2 C for 72 hrs. -20 C for 48 hrs & 42+/-2 C (Stable even after 2 freeze thaw cycles) Summary: Heat stable vaccine which can be stored below 25 C & does not need refrigeration. Was developed to reduce cold storage space for RV vaccines supplied for NIPs 2 . Reconstituted vaccine must be used immediately. If not used immediately, it can be held for a period of maximum 6 hours provided a syringe is used to cap the opening of the vial adapter & the entire assembly is stored at 2-8 C 2 . Important if Multi dose (5 ml) packs are supplied. Sameer P. Naik et al. Stability of heat stable, live attenuated Rotavirus vaccine (ROTASIIL). Vaccine 35 (2017) 2962-2969. Rotasiil PI Multidose pack. 20014546/1. RotaTeq PI. MSDIN 11/16. RotaTeq storage conditions (from PI) 3 To be stored & transported at 2-8 C. When out of refrigeration or <= 25 C, administration may be delayed for up to 48 hours.

20. BRV-PV Phase 3 Efficacy & Safety Trial in India 1 Phase 3 Efficacy data-India 1 (Kulkarni et al_2017) 1 : * Vaccine transported & stored at 2-8 C ** . BRV-PV Phase 3 study in India. Total 7500 infants (V=3749 & P=3751). No restrictions on OPV, DTP-HB-Hib, Breastfeeding. Vaccine Efficacy- Pr. Analysis (PPP): Min. no. of cases needed for analysis. VSRVGE = 60.5% (VS>16). SRVGE = 36% (VS>11). Vaccine Efficacy- Sec. Analysis (PPP ): End of 2 years. VSRVGE = 54.7% ( VS>16). SRVGE = 39.5% (VS>11). IgA seroresponse (>= 3 fold rise): 33.6% (BRV-PV group). Safety Profile : Similar in both vaccine & placebo groups. SAE: 12 cases of GE 7 days post vaccination (V=7, P=5). Only 1 tested positive for RV antigen in stool by ELISA. Genotype did not reveal any vaccine strain. Authors’ note (Verbatim): “Since this was a pivotal trial to support licensure, the study vaccine was transported & stored at 2-8 C out of caution”. Kulkarni et al. A randomized Phase III clinical trial to assess the efficacy of a bovine human reassortant pentavalent rotavirus vaccine in Indian infants. Vaccine (2017). https:// doi.org/10.1016/j.vaccine.2017.09.014 .

21. BRV-PV & 116E Phase 3 Efficacy, Immunogenicity & Safety Trials [ Snapshot] (Not head to head comparison trials) Isanka et al. Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger. N Engl J Med 2017;376:1121-30. Kulkarni et al. A randomized Phase III clinical trial to assess the efficacy of a bovine human reassortant pentavalent rotavirus vaccine in Indian infants. Vaccine (2017). https:// doi.org/10.1016/j.vaccine.2017.09.014 . Zade et al. Bovine Rotavirus Pentavalent Vaccine Development in India. Vaccine 32S (2014) A124-A128. Bhandari N et al. A Dose-Escalation Safety and Immunogenicity Study of Live Attenuated Oral Rotavirus Vaccine 116E in Infants: A Randomized, Double-Blind, Placebo-Controlled Trial. The Journal of Infectious Diseases 2009; 200:421–9. Bhandari N et al. Efficacy of a Monovalent Human-Bovine (116E) Rotavirus Vaccine in Indian Infants: A Randomized Double Blind Placebo Controlled Trial. Lancet. 2014; 383 (9935): 2136–43 . Lokeshwar et al. Immunogenicity and safety of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine (PRV) in Indian infants. Human Vaccines & Immunotherapeutics 9:1, 178–182; January 2013; c 2013. Narang et al. Immunogenicity, reactogenicity and safety of human rotavirus vaccine (RIX4414) in Indian infants. Human Vaccines 5:6, 414-419; June 2009 Bhandari N et al. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life . Vaccines 32S (2014) A110-A116 . BRV-PV (Niger data) BRV-PV (India data) 116E (India data) RV5 (India data) RV1 (India data) Efficacy (< 2 years) SRVGE (VS>11) 66.7% [PPP] 1 1 year Efficacy data not published 56.4% [PPP] 5 No study in India No study in India VSRVGE (VS>15) 78.8% [PPP] 1 1 year Efficacy data not published 49.8% [PPP] 5 Efficacy (at 2 years) SRVGE (VS>11) Not published 39.5% [PPP] 2 55.1% [PPP] 8 No study in India No study in India VSRVGE (VS>16) Not published 54.7% [PPP] 2 57.2% [PPP] 8 Immunogenicity Not published 60% - Phase 2b 3 33.6% - Phase 3 2 89.7% - Phase 2a 4 39.9% - Phase 3 5 83% [India] 6 58% [India] 7 Serotype specific Efficacy Not published Overall efficacy against G1,G2,G3,G9,G12 = 38.9% 1 [ -ve CI G3,G9,G12] Negative CI values for G1P[8], G12P[8] & G9P[4] 5,8 55.6-93.3% [G1,G2,G3,G4,P[1] 6 Safety Tolerable safety profile 1 12 cases of GE 7 days post vaccination (V=7, P=5) 2 20 cases of G9P[11] GE seen after dose 1 & 2 cases post dose 2 of II6E RV vaccine . All cases were mild or moderate by VS 5 Tolerable safety profile 6 Tolerable safety profile 7

22. Introduction of RotaTeq in GAVI-Eligible Countries Rwanda May 2012 Nicaragua Oct 2006 The Gambia Aug 2013 Burkina Faso Oct 2013 Mali Jan 2014 Cote d’Ivoire Sao Tome 2016 In same year as US licensure (2006) Merck-Nicaragua MoH partnership implemented 1.3 million doses donated over 3 yrs 3 dose vaccine effectiveness after 2 years of follow-up (2007-9) against severe rota (≥11) was 85% (66,93) in those <1 year Hospitalizations for diarrhea in <1 year olds decreased by 51% in 2014 Diarrhea hospitalizations declined among older children not vaccinated, suggesting indirect protection Lancet Global Health 2016 PIDJ 2011 3 dose vaccine effectiveness in those < 2 years (2007-8) 46% (18,64) against rota –related hospitalization and IV fluid 58% (30,74) against severe rota disease (≥11) 77% (39,92) against very severe rota disease ( ≥15) JAMA 2009

23. RotaTeq in NIP in Rwanda (Effectiveness of RV5)_2016 1 1. Jacqueline E. Tate , Fidele Ngabo et al. Effectiveness of Pentavalent Rotavirus Vaccine Under Conditions of Routine Use in Rwanda. Clinical Infectious Diseases® 2016;62(S2): S208–12. Overall VE = 75%

24. RotaTeq: – Data on G9 & G12 (Ref: RotaTeq Product Insert MSDIN 11/16)

25. RotaTeq Updated PI (Information on G9) – [G1-G4 & G9 Efficacy at 1 year-REST] 1 1. RotaTeq PI. MSDIN 11/16. The vaccine was specifically designed to prevent rotavirus gastroenteritis caused by the individual G-serotypes included in the vaccine (G1, G2, G3, and G4); P1A[8 ] was included in the vaccine to potentially provide cross-protection against nonvaccine G-serotypes that may contain P1A[8]. Based on limited data, the efficacy against any severity of gastroenteritis caused by the non-vaccine G serotype (G9) was 74.1%.

26. RotaTeq Updated PI (Information on G12) [Effectiveness against G12 & protection until 7 th year of Life] 1 1. RotaTeq PI. MSDIN 11/16

27. ACIP – Grading for RV5

28. ACIP: Moving from Evidence to Recommendation Pentavalent Rotavirus Vaccine gets Category A recommendation Overall evidence type Overall evidence type across all critical outcomes 1 Values and preferences (assume a set of values for each outcome considered) OUTCOME VALUES AND PREFERENCES Rotavirus diarrhea Relatively lower value Severe rotavirus diarrhea High value Hospitalization for rotavirus diarrhea High value Intussusception High value Other serious adverse events High value Cost effectiveness Relatively lower value Draft recommendation We recommend vaccination of infants with three doses of rotavirus vaccine. Recommendation category Category A Ahmed F. U.S. Advisory Committee on Immunization Practices Handbook for Developing Evidence-based Recommendations. Version 1.2. Atlanta, GA: Centers for Disease Control and Prevention (CDC); 2013. Available from http://www.cdc.gov/vaccines/acip/recs/GRADE/about-grade.html#resources RotaTeq: Type 1 GRADE A recommendation

29. WHO – Grading of Scientific Evidence

30. WHO Grading of Scientific Evidence: Higher score for RV5 in preventing severe rotavirus diarhhoea in High Mortality Countries What is the effect of RV1 compared to placebo for preventing severe rotavirus diarrhoea in high-mortality countries? What is the effect of RV5 compared to placebo for preventing severe rotavirus diarrhoea in high-mortality countries? What is the effect of RV1 compared to placebo for preventing severe all cause diarrhoea in high-mortality countries? What is the effect of RV5 compared to placebo for preventing severe all cause diarrhoea in high-mortality countries? Final numerical rating of quality of evidence 3* 4 3* 4 Statement on quality of evidence Further research is likely to change the estimate of effect Further research is very unlikely to change our confidence in the estimate of effect Further research is likely to change the estimate of effect. Further research is very unlikely to change our confidence in the estimate of effect Conclusion We are moderately confident that use of RV1 in high mortality countries reduces the rate of severe rotavirus diarrhoea We are confident that use of RV5 in high mortality countries reduces the rate of severe rotavirus diarrhoea We are moderately confident that use of RV1 in high mortality countries reduces the rate of severe all-cause diarrhoea We are confident that use of RV5 in high mortality countries reduces the rate of severe all-cause diarrhoea * Downgraded due to indirectness as trials were conducted in Malawi and South Africa: generalization to high--‐mortality countries is difficult. http://www.who.int/immunization/documents/positionpapers/en/ . Accessed 7th Jan 2018.

31. RotaTeq Product Strengths

32. Product Highlights - RotaTeq Regulatory attributes: More than 10 years post US licensure 1 . 222 million doses distributed worldwide 1 . Registered in approximately 120 countries 1 . Extensive drug discovery & development process spanning 13 years 1 . Quality attributes: Highest grading by the Advisory Committee on Immunization Practices to CDC , USA for quality of evidence across major clinical outcomes for Rotavirus diarrhea (graded as a Type 1 GRADE A product ) 2 . Higher rating compared to RV1 for quality of evidence by World Health Organization for preventing severe Rotavirus diarrhea in high mortality countries 3 . Scientific attributes : Only formulation with 5 Rotavirus strains which account for 88% of infections worldwide 4 . Proven real world effectiveness of 70-95% in approximately 3 lakh subjects across the globe 5-8 . Large scale safety data in 70,000 subjects spanning 11 countries across 3 continents with no increased risk of intussusception in vaccine vs. placebo 9 . High & consistent efficacy with 3 doses across all vaccine serotypes – 94% reduction up to 3.1 years in the combined incidence of hospitalizations/Emergency Department visits for RGE 9,10 . Commercial formulation attributes : Ready to use liquid formulation stable at 2-8 degrees 11 . ( as on Q4 2017)

33. Awards - RotaTeq RotaTeq has been recognized externally 12 : The Lancet Paper of the Year - (2006). Vaccine Industry Excellence Award for Best Prophylactic Vaccine - (2009). Prix Galien – (US , 2010). References: RotaTeq Product highlights. MSD data on file. Internal global communication dated 3 rd Feb 2016 & 2 nd Feb 2018. Ahmed F. U.S. Advisory Committee on Immunization Practices Handbook for Developing Evidence-based Recommendations. Version 1.2. Atlanta, GA: Centers for Disease Control and Prevention (CDC); 2013. Available from http://www.cdc.gov/vaccines/acip/recs/GRADE/about-grade.html#resources http://www.who.int/immunization/documents/positionpapers/en/ . Accessed 7th Jan 2016 . Santos et al. Global distribution of rotavirus serotypes/ genotypes and its implication for the development and implementation of an effective rotavirus vaccine. Rev. Med. Virol . 2005; 15: 29–56. Patel M et al. Duration of protection of Pentavalent Rotavirus vaccination in Nicaragua. Pediatrics 2012;130:e365–e372. Clark MF et al. Direct & Indirect impact on RV positive & all cause GE hospitalizations in South Australian children following the impact of RV vaccination. Vaccine 29 (2011) 4663-4667. Vesikari , Uhari et al. Impact & Effectiveness of Rotateq vaccine based on 3 yrs surveillance following introduction of a Rotavirus Immunization Programme in Finland. Pediatr Infect Dis J 2013;32:1365–1373. Wan-Chi Chang et al. Effectiveness of 2 Rotavirus vaccines against Rotavirus disease in Taiwanese infants. Pediatr Infect Dis J 2014;33:e81–e86 . Vesikari T, et al. N Engl J Med. 2006;354:23 – 33 . Vesikari et al. Efficacy of the pentavalent rotavirus vaccine, RotaTeq®, in Finnish infants up to 3 years of age: the Finnish Extension Study. European Journal of Pediatrics, 2010, 169:1379–1386. RotaTeq PI. MSDIN 07/14 . MSD Data on File. RotaTeq Global Strategy & Scientific Positioning 2016 MAP ppt.

34. THANK YOU !! Contact me for any queries / suggestions at [email protected] Acknowledgements: Dr Puneet Kalra , Medical Advisor, MSD