Updates on Rotasiil development

Transcription

1 Updates on Rotasiil development 13 th International Rotavirus Symposium Minsk, Belarus 30 August 2018 Dr Sajjad Desai MD Serum Institute of India Pvt Limited, Pune

2 Rotasiil Bovine-human reassortant strains received from NIH Sterile, pentavalent, lyophilized powder 2.5 ml antacid as diluent Rotavirus serotypes G1, G2, G3, G4 and G9 at FFU/Serotype/dose. Three doses at 6, 10 and 14 weeks of age

3 Serotypes & Severity G1, G2, G3, G4 and G9 serotypes cause over 90% of rotavirus disease worldwide G9 The emerging serotype associated with a significantly longer duration and higher diarrhea longer duration of vomiting increased hospitalization rate more-severe dehydration frequency of C. Linhares. CID 2006:43; Tarun Saluja Hum Vaccin Immunother Mar; 13(3): Linhares et al. 2011

4 Three dose Schedule Natural rotavirus infection confers protection against subsequent infection and protection increases with each new infection [Velázquez et al, NEJM, 1996]

5 Thermostable vaccine Lyophilized vaccine 36 months at 25 o C 18 months at 40 o C Reconstituted Vaccine 5 ±3 o C for six hours Assures potency during power failures and transport Recommended storage 25 o C for 30 months First heat-stable vaccine in the world 13

6

7

8

9 USPTO announced humanity award to NIH patent for rotavirus vaccine developed in partnership with SIIPL

10 Need for antacid Rotavirus is an acid labile virus To protect the attenuated vaccine in the gastric acid, the acid needs to be neutralized Rotasiil has 2.5 ml antacid as diluent Ensures survival of vaccine virus during gastric ph

11 Preclinical & Clinical Development Phase Objective Number of doses Subjects Toxicity Safety Single and repeated I Safety 1 Rabbits and Rats Adults Toddler Infant II Safety, Immunogenicity 3 Infant Safety, Immunogenicity 3 Infant III Efficacy, Safety 3 Infant (India) III Efficacy, Safety 3 Infant (Niger) III Lot-to-Lot consistency Non-interference with EPI vaccines 3 Infant (India)

12

13 Phase III efficacy clinical trials Two studies : One in India and another in Niger (MSF) Similar study designs Sample size India 7500 Niger 7770 Storage in Niger 25 C in Maradi Ambient temperature at dispatch to vaccination sites

14 Niger Clinical Trial Results Vaccine Efficacy Type of Gastroenteritis Rotasiil Placebo Vaccine Efficacy Very severe RVGE % SRVGE % The New England Journal of Medicine 376;12 : March 23, 2017 Vaccine Safety Events Placebo P Value SAE One participant had confirmed intussusception, 542 days after receiving the third dose of RotaSIIL. Vaccine 36 (2018)

15

16 Indian Clinical Trial Results Type of Gastroenteritis Vaccine efficacy (Primary Analysis) (n=3749) Placebo (n=3751) Vaccine Efficacy p-value Very severe RVGE % SRVGE % Type of Gastroenteritis Vaccine efficacy (Final Analysis) Placebo Vaccine Efficacy p-value Very severe RVGE % SRVGE % < Better efficacy even in very severe RVGE - the highest risk of dehydration, hospitalization and deaths

17

18 Comparative Efficacy SRVGE Very severe RVGE RVGE Vaccine Country ITT% 95% CI PP % CI PP % CI Africa 40.3 (20.6, 55.3) 40.7 (3.3, 64.2) 30.5 (16.7, 42.2) RotaTeq Rotarix Asia 47.8 (21.9, 65.6) 70 (31.8, 88.3) 42.5 (21.2, 58.4) Mali 1 (-431.7, 81.6) Bangladesh 42.7 (10.4, 63.9) Malawi 44.7 (19.2, 68.5) 34.7 (7.7, 53.5) Bangladesh 48 (27, 63) 45.2 (26.3, 59.3) ROTAVAC India 54.7 ( ) 54.4 (-18.3, 82.6) 36.4 (21.6, 45.3) BRV-PV India 41.7 (21.1, 57.3) 60 (17.7, 81.0) 28 (11.1, 42.2) Niger 69.1 (55.0, 78.7) 78.8 ( ) 34.5 (17.3, 48.1) Armah GE et al 2010; Zaman K et al 2010 Cunliffe et al Vaccine 2012; Armah et al Clin Infect Dis 2016 Nita Bhandari et al. Lancet Jun 21; 383(9935): Results comparable to other rotavirus vaccines

19 Phase III EPI Study 1500 infants in India Lot-to-lot consistency was demonstrated No interference with EPI vaccines was seen IgA GMCs were (95% CI ) in the combined Rotasiil group and (95% CI ) in the Rotarix group

20

21 Current Status Licensed in India in December Introduced in EPI in Jharkhand in April > 1 million doses distributed Three PSURs prepared so far; no safety concern reported Phase IV studies planned 13

22 Live, Liquid Pentavalent Rotavirus vaccine

23 Product Profile Ready-to-use liquid vaccine with same strains and manufacturing process as Rotasiil Volume 2 ml, Stored at 2-8 C

24 Preclinical & Clinical Development Phase No. of doses Vaccine recipients Status Toxicity Single and repeated Rabbits and Rats Completed I 1 Adults Completed II/III 3 Infants Completed; analysis ongoing

25

26 Summary Rotasiil is found highly safe and efficacious No safety concern reported since licensure Liquid formulation Phase II/III trial results are awaited

27 Acknowledgement Participants and Parents Investigators and site staff IAC Members DSMB Members

28