Review of the evidence: vaccine safety and co- administra5on. Dr. Heidi Meyer

Transcription

1 Review of the evidence: vaccine safety and co- administra5on Dr. Heidi Meyer 1

2 Outline Safety profiles and key data* Inac5vated Vero cell vaccines (IXIARO) Live ajenuated vaccines (CD.JEVAX) Chimeric vaccine (IMOJEV) Summary Co- administra5on with measles containing vaccines *Focus on children and serious AEs 2

3 IXIARO INACTIVATED VERO CELL VACCINES 3

4 Inac>vated Vero cell vaccine - IXIARO Safety: 14 publica5ons including 1 regulatory report Primary and booster immunisa>on Adults in 7 RCT / Pooled safety analysis from 3558 IXIARO vaccinees compared to control groups (Dubischar- Kastner et al 2010; EPAR 2012) Adults in 10 RCT / Pooled safety analysis of 4043 vaccinees and 1 year post- marke5ng surveillance data (Schuller et al 2011) Primary immunisa>on in children in 2 RCT (Kaltenboeck et al 2010; EPAR 2013) 4

5 data in children Open- label, randomized, ac>ve- controlled Phase III study in the Philippines Rates of SAEs or medically ahended AEs up to day 56 (stra>fied by dose and age) Age group IXIARO 0.25 ml IXIARO 0.5 ml Prevnar HAVRIX months to < 1 year 1 year to < 3 years 3 years to < 12 years (N=131) 38.2% (N=640) 26.7% (N=100) 7.0% - (N=64) 42.2% - - (N=213) 22.1% (N=301) 8.0% 12 years to < 18 years - (N=240) 1.7% - (N=100) 5.9% - (N=80) 3.8%. - Between Day 56 and Month 7, 1 fatal SAE of disseminated intravascular coagula5on was reported for a 12- year- old subject (IXIARO 0.5ml); the event was considered not related to study vaccine by the inves5gator. EPAR,

6 safety 12 months post-marketing data ( ) on 246,687 doses distributed in Europe, USA and Australia: 25 adverse drug reac5ons (ADR ) reported; Overall repor5ng Most frequently affected system organ class (SOC) skin and subcutaneous 5ssue disorders 24% mainly rash general disorders and administra5on site condi5ons 20% mainly fever nervous system disorders 20% mainly headache gastrointes5nal disorders 10% doses JE- VAX: 8.4/100,000 doses Adverse events of special interest (AESI): 10 cases considered possible hypersensi5vity reac5ons including rash (4 cases) Schuller et al

7 Summary Safety : In children and adolescents from 2 months to <18 years: as regards profile frequency comparable and severity with of licensed local and vaccines systemic (pneumococcal AE. and Hep A vaccines) below Systemic No vaccine 1 year, AEs related fever were was mostly SAE the or most death mild to common reported moderate, reac5on in RCTs they up occurred to 7 months more frequently in children Adults: No vaccine related SAE or death reported in RCTs up to 7 months Adults: vaccine Comparable except tolerability for local reac5ons. and reactogenicity Significantly with placebo (adjuvant alone) and MBDV JE reac5ons reported lower frequency of severe local for IXIARO than MBDV vaccine. No Poten5al vaccine related SAE or death reported in RCTs up to 7 months risk of rare AE including hypersensi5vity/allergic reac5ons Pregnancy : Very limited informa5on, but pregnancy is not a contraindica5on 7

8 CD.JEVAX

9 Live ahenuated vaccine CD.JEVAX Safety: 18 publica5ons including 1 poster presenta5on Safety Primary : 18 publica5ons vaccina5onincluding 1 poster presenta5on Primary (Feroldi et al. 2014, Kim et al ( Booster poster), vaccina5on Liu et al. 1997) (Choi et al. 2013) Co- administra5on Post marke5ng surveillance with Measles data vaccine (Liu et al. in 12014) RCT (Gatchalian et al. 2008) Case reports (Jia et al 2011) 9

10 Live ahenuated Comparison of IMOJEV and CD.JEVAX in 2 observer - blind RCTs Children aged 9-18 months or months Approximately 280 children randomized per vaccine group 2 cases of pyrexia reported in the CD.JEVAX group as SAE were judged vaccine related slightly moderate Frequency higher in of the common CD.JEVAX injec5on group site compared and systemic to IMOJEV; vaccine mostly reac5ons mild were to RCT in 26,239 children in 180 health 10

11 reported rate in one year olds 59.1% of 44.4% vaccine alone Concomitant administra5on in 41.3% subjects: thereof 47.9% with Measles Rubella, 13% with - AE reported AE SAEs ( 38.6 C) Liu et al

12 Summary Safety Children from 9 months to 6 years: Moderately higher frequency of : CD.JEVAX than local and systemic AEs aker 2 vaccine- related IMOJEV. SAE reported in 1 recent RCT (pyrexia Huge ) post marke5ng experience, however underrepor5ng is to be Poten5al expected risk hypersensi5vity/allergic of rare adverse and neurologic reac5ons reac5ons including No published informa5on

13 IMOJEV CHIMERIC VACCINE 13

14 Chimeric vaccine - IMOJEV and 1 poster Primary and booster immunisa>on in children Unvaccinated children in 3 RCTs (Feroldi et al 2012, 2014; Kim et al 2013/Poster) Unvaccinated and MBDV- primed children in 1 RCT (Chokephaibulkit et al 2010) IMOJEV- primed children in 1 RCT (Feroldi et al 2013) Primary and booster immunisa>on in adults Adults in 3 RCTs (Nasfeld et al 2010, Torresi et al 2010) 14

15 IMOJEV safety data in children HepA vaccine in 2 RCTs (Thailand, Philippines) VZV vaccine in 1 RCT (Philippines) Children aged between 9-24 months Approximately 1600 children vaccinated with IMOJEV No vaccine- related SAE reported for IMOJEV Common vaccine reac5ons were comparable between IMOJEV and licensed Hep A and VZV vaccine groups and across studies, mostly mild to moderate 15

16 Summary Safety - IMOJEV from 12 months vaccines (Hep A and VZV vaccines) frequency No vaccine profile and related severity SAE of local or death and systemic reported AE. in RCTs (up to 7 months) as regards Adults: Comparable tolerability and reactogenicity with placebo and MBDV JE Adults : vaccine for local Significantly reac5ons. lower of local with placebo except reac5ons reported for IMOJEV reported in RCTs (up to 7 than No Poten5al risk of neurologic months) in pregnant women and immunocompromised data Poten5al Acceptable safety contraindicated pregnant women profile and immunocompromised contraindicated Acceptable safety profile 16

17 Poten>al risk of neurologic events Neurologic events including cases of encephali5s with temporal assessment not illness that occurs in temporal associa5on with JE vaccina5on to rule out this possibility. Coincidental cases of encephali5s should be expected (and have been reported), especially during mass campaigns. An appropriate inves5ga5on will help maintain confidence in the vaccina5on program. 17

18 Inactivated JE-VAX adsorbed IXIARO CD.JEVAX attenuated CD.JEVAX Substrate Mouse brain Vero cells Primary hamster kidney cells known Excipients effects / residuals with known effects urticaria, angiooedema or urticaria, angiooedema or respiratory distress encephalitis, encephalopathy, convulsions myelitis, residual mouse brain protein /100,000 (US, mostly adults) /100,000 (US, mostly adults) children) 0.0 (US, mostly adults) Protamine sulphate as residual adults) meningism, headache (2x), migrane, only migrane, only neuritis one of serious) considered serious) IMOJEV Chimeric IMOJEV Vero cells Gelatine Glutamic acids (?) Antibiotics (?) 2.8/100,000 (mostly children) 1.3/1,000,000? No postmarketing data yet? 18

19 Co- Administra5on MMR *Data on co- administra5on with available travellers vaccines 19

20 MEASLES VACCINE 20

21 Concomitant use of CD.JEVAX with measles vaccine in children 8-10 months Safety: No vaccine related SAEs observed (Follow- Up 4 weeks) Co- administra5on with MV raised no specific safety concerns Safety: No Limita>ons vaccine related of the study SAEs observed (Follow- Up 4 weeks) reac5ons Vaccine- related systemic reac5ons : Follow- expected up only 7days for systemic reac5ons to peak between 5-14 days both Immunogenicity: Co- administra5on are live ajenuated of CD.JEVAX vaccines in children 8-10 months CD.JEVAX of age as acceptable SP rates and GMTs Gatchalian Victor et al 2014 et al

22 CHIMERIC VACCINE AND MMR 22

23 IMOJEV co- administra>on with MMR RCT in children aged months in Taiwan; (Huang et al 2014) Safety: No vaccine- related SAEs, no immediate AEs or AEs leading to withdrawal In general, the frequency of systemic reac5ons was comparable in the coadministra5on group and the group receiving MMR alone. Rash was reported more frequently in the co- administra5on group Safety Co- administra>on with MMR vaccine in children raised no safety concern Immunogenicity : coadministra5on No In Rash general, vaccine- related was reported the group frequency demonstrated more SAEs, and frequently the no of systemic immediate group receiving in reac5ons the AEs co- administra5on or MMR AEs was leading alone. comparable to group withdrawal in the Co- administra>on with MMR vaccine in children raised no safety Persistence demonstratedagainst for SP JEV rates observed and GMT/GMC Lower aker 1 year: seroprotec>on rates 23

24 Conclusions Given current scope of use, schedules, and primary concerns of live vaccines co- administered together, of most relevance is co- administra5on CD.JEVAX and IMOJEV with live measles- containing vaccines Further assessment, par5cularly with MR, is warranted Available data on CD.JEVAX/MV and IMOJEV/MMR suggest co- administra5on with these vaccines is acceptable. 24

25 Back- up slides 25

26 IMOJEV safety data in children No vaccine related SAEs reported for IMOJEV Common vaccine reac5ons were generally comparable between IMOJEV and HepA Study No 2: vaccine children related aged SAEs reported months for IMOJEV Common No vaccine (primed vaccine related IMOJEV reac5ons SAEs reported N=345; were generally naïve primed comparable IMOJEV and N=46, unprimed between naïve IMOJEV with VZV IMOJEV and N=59) HepA Common vaccine reac5ons were generally comparable between IMOJEV and VZV naïve vaccine groups. Fever occurred rate in primed more children frequently was in comparable IMOJEV primed with children VZV immunized than in naïve children. and 1 was headache, all resolved with medica5on Common vaccine reac5ons were generally comparable between IMOJEV and VZV naïve vaccine groups. Fever occurred more frequently in IMOJEV primed children than in naïve children. Fever rate in primed children was comparable with VZV immunized naïve children Severe (Grade 3) reac5ons were reported for 8/391 children in the IMOJEV groups, 7 were fever and 1 was headache, all resolved with medica5on 26