This document summarizes a presentation on hexavalent vaccines given by Dr. Gaurav Gupta. It discusses the efficacy, safety, and immunogenicity data from clinical trials of hexavalent vaccines compared to whole-cell and other combination vaccines. Indian data is presented from a clinical trial of a hexavalent vaccine administered at 6, 10, and 14 weeks of age showing high rates of seroprotection and a favorable safety profile. Schedules using hexavalent vaccines that include vaccination at birth allow for a simplified 0, 3, +/-1 year immunization schedule for hepatitis B.

1. The new kid on the block
Hexavalent Vaccines!
Dr Gaurav Gupta,
Pediatrician,
Mohali (Chandigarh)
RajPedicon - Nov, 2016

2. Conflict of Interest
• Received grants from various vaccine
manufacturers including
– Sanofi Pasteur
– GSK
– Abbott
– Novartis

3. WIIFY
• Need for Combination Vaccines
• Safety, efficacy of Hexavalent Vaccines
• Indian Data
• Scheduling
• Some Unique Features

4. What I won’t be talking about?
• aP versus wP
• Components
• Pricing

5. Combination Vaccines – Why?
• Simplified Immunization Schedule
• Less injections – Complications
• Better Compliance
• Lesser administration time/ costs

6. Combination vaccines – Why not?
• Technically difficult
• Expensive

7. Hexavalent Vaccines across the World
• Hexavac – discontinued
• Infanrix Hexa – GSK – with lyophilised Hib
• Hexaxim – Fully liquid 6 in 1 with DPT + Hep B
+ Hib + IPV

8. Hexavalent Vaccines across the World
• Hexavac – discontinued
• Infanrix Hexa – GSK – with lyophilised Hib
• Hexaxim – Fully liquid 6 in 1 with DPT + Hep B
+ Hib + IPV

9. Efficacy
• As compared to other aP vaccines
• As compared to wP vaccines, specifically
against Pertussis

10. HEXAXIM® immunogenicity assessment - Overview
● 8 primary series studies
● 3 primary schedules (6, 10 & 14 weeks; 2, 3 & 4 and 2, 4 & 6 months)
● With or without hepatitis B vaccination at birth
● versus different control vaccines:
• wP-based combination vaccines
• PENTAXIM® + standalone hepatitis B vaccine
• INFANRIX-HEXA (DTaP-IPV-HBV//Hib***)
• Concomitantly with other routine pediatric vaccines
*Tritanrix®-HepB/Hib **CombAct-HIB® *** Infanrix Hexa®

11. 0
20
40
60
80
100
D T PT FHA PV1 PV2 PV3 HBsAg Hib
Immunogenicity v/s whole cell-based vaccines
HEXAXIM® induces high immune responses similar
to those of wP-based combination vaccines
Seroprotection/seroconversion rates after the 3rd dose of HEXA or a wP-based combination
vaccine in infants vaccinated at 6,10 &14 weeks of age
(South Africa)1 (No HepB vaccine at birth, no concomitant vaccine)
Seroprotection/
Seroconversionrates(%)
D T PT FHA PV1,2,3 HBsAg Hib
 0.01 IU/mL 4-fold increase
(pertussis antigens)
1/dil  8  10 mIU/mL  0.15 µg/mL
98 96 100 100
94
83
93
58
100
93
99 100 100 98 96 95 95
100
HEXAXIM® 1
n=220
DTwP//Hib* + OPV + Hep B vaccine 1
n=212
* CombAct-HIB® [1] Madhi et al. PIDJ, 2011;30(4)

12. 0
20
40
60
80
100
D T PT FHA PV1 PV2 PV3 HBsAg Hib
The immune response to all HEXAXIM® antigens is high and similar
to that of PENTAXIM® co-administered with standalone hepatitis B vaccine
Seroprotection/
Seroconversionrates(%)
D T PT FHA PV1,2,3 HBsAg Hib
 0.01 IU/mL 4-fold increase
(pertussis antigens)
1/dil  8  10 mIU/mL  0.15 µg/mL
100 100 100 100
92 93 93 90
100 100 100 100 100 100 99 100
95 97
HEXAXIM®
n=260
PENTAXIM® + Hep B vaccine
n=271
[5] Tregnagui et al. PIDJ, 2011;30(6)
Seroprotection/Seroconversion rates after the 3rd dose of HEXA or PENTA
in infants vaccinated at 2, 4 & 6 months of age
(Argentina)5 (No Hep B vaccine at birth, no concomitant vaccine)
Immunogenicity Vs PENTAXIM®

13. Completion of a 3-dose primary series and a booster administration in the first 2 years of life with the investigational
DTaP-IPV-HB-Hib vaccine in toddlers induced strong Ab responses towards the antigens included in the
investigational vaccine which persisted in significant percentages of children at 3.5 years of age

14. Safety
• Safety as compared to wP vaccines

15. HEXAXIM® safety assessment - Overview
Evaluated in 20 clinical trials in more than 6000 infants and toddlers
● 18,000 doses administered to > 6000 infants in 20 clinical trials
● With or without hepatitis B vaccination at birth
● versus different control vaccines:
• wP-based combination vaccines
• PENTAXIM® + standalone hepatitis B vaccine
• INFANRIX-HEXA (DTaP-IPV-HBV//Hib***)
• Concomitantly with other routine pediatric vaccines
[19] Sanofi Pasteur. Data on file

16. Solicited reactions after any dose of HEXAXIM® or DTwP-HepB//Hib*
in infants vaccinated at 2,4 & 6 months of age (Mexico & Peru)3 (No concomitant vaccine)
0
20
40
60
80
100
Pain Red Swell A Fever Vom Crying Somnol Anor Irr
The reactogenicity of HEXAXIM® is consistently lower than that of
wP-based combination vaccines
Gr3: grade 3 *Tritanrix®-HepB/Hib [3] Macias et al. PIDJ, 2012;31(8)
78 94
59 71
17 36
3 6
43 67
1 6
75 93
4 6
30 31
2 3
78 92
3 5
57 69
5 6 3 5
82 92
46 59
6 10
Reactionincidence(%)
HEXAXIM®
n=1422
DTwP-HepB//Hib*
n=711
Any Gr3 Any Gr3 Any Gr3 Any Gr3 Any Gr3 Any Gr3 Any Gr3 Any Gr3 Any Gr3
Pain Redness Swelling Fever Vomiting Crying Somnolence Anorexia Irritability
Tolerability Vs. wP-based combination vaccines

17. Safety in primary and booster series
Key points
Well tolerated under various primary schedules (6-10-14 weeks, 2-3-4
and 2-4-6 months)
Better tolerated than wP-based combination vaccines
Comparable to other licensed aP-based combination vaccines
(PENTAXIM®, Infanrix Hexa)
The safety and reactogenicity - not affected by the administration of
hepatitis B vaccine at birth
* Infanrix® Hexa

18. Indian Data

19. IMMUNOGENICITY AND SAFETY OF
DTaP-IPV-HB-PRP-T COMBINED
VACCINE GIVEN AT 6, 10 AND 14
WEEKS OF AGE IN INFANTS FROM
INDIA, WHO PREVIOUSLY RECEIVED
A DOSE OF HEP B VACCINE AT BIRTH
Presenting Author: Prof Sanjay Lalwani
Date : 23 January 2016
Venue : PEDICON – Hyderabad
WHO Universal Trial Number (UTN): U1111-1127-6936

20. Immunogenicity (Primary objective): % Seroprotection
and Vaccine Response one month after 3 doses
99.30% 100%
93.80%
99.30% 100% 100% 100% 100% 100%
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
80.00%
90.00%
100.00%
Anti-D (≥
0.01 IU/mL )
Anti-T (≥
0.01 IU/mL )
Anti-PT
(Vaccine
response)
Anti-FHA
(Vaccine
response)
Anti-Polio 1
(≥ 8 (1/dil)
Anti-Polio 2
(≥ 8 (1/dil)
Anti-Polio 3
(≥ 8 (1/dil)
Anti-Hep B
(≥ 10
mIU/mL)
Anti-PRP (≥
0.15 μg/mL)
20

21. Safety: Solicited reactions from D0 to D7, any
grade, after each injection (in %)
21
19%
4.60%
10.30%
13.80%
3.40% 3.40%
11.90%
0.60%
6.50%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Tenderness Erythema Swelling
Post Dose 1 Post Dose 2 Post Dose 3
7.5%
9.8%
16.1%
9.8%
6.9%
22.4%
8.6%
3.4%
9.8%
3.4% 3.4%
16.7%
7.1%
3.0%
7.7%
3.0% 3.0%
12.5%
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
80.0%
90.0%
100.0%
Fever Vomiting Abnormal
Crying
Drowsiness Loss of
appetite
Irritability
Post Dose 1 Post Dose 2 Post Dose 3
 54.6% experienced at least 1 solicited
systemic reaction.
 Most frequently reported systemic
reaction was irritability (36.2%)
 19.0% of subjects reported fever ; no
Grade 3 fever reported
Injection site reactions
 37.9% experienced at least 1 solicited
injection site reaction, most frequent being
tenderness (30.5%).
 2.9% of subjects reported Grade 3 reactions
 The incidence lowered with successive
doses with no Grade 3 reaction reported
after the third dose
Systemic reactions

22. What Schedule works?

23. HepB seroprotection rates (%≥10mIU/ml) and GMT
(IU/mL) following different HepB immunization regimen
HB
regimen
Infant series
product &
regimen
Post Infant series
responses
Toddler
product
Pre
toodler
booster
Post
toddler
booster
0 + 2 + 1 HXM 3-58 97,2% - 401 HXM (11/12) 87,6% - 76 96,4% - 1,370
0 + 3 + 0
HXM 2-4-611 99,2% - 1,148 -
HXM 2-4-612 99,2% - 986 -
0 + 3 + 1
HXM 2-3-45 94,0% - 149 HXM (15/18) 80,7% - 44 97,3% - 1,379
HXM 2-3-49 97,5% - 242
96,1% - 267
HXM (12)
90,1% - 76
91,4% - 95
98,9% - 2,230
98,9% - 2,233
HXM 2-3-410 95,7% - 207 HXM (11/18) Ongoing Ongoing
HXM 2-4-62 98,3% - 1,142 HXM (15/18) 89,8% - 93 99,4% - 2,553
HXM 6-10-143,4 95,7% - 330 HXM (15/18) 78,9% - 51 98,5% - 4,630
1 + 3 + 0
HXM 6-10-147 100% - 2,491 -
HXM 2-4-66 99,5% - 2,477 -
1 + 3 + 1
HXM 6-10-143,4 99,0% - 1,913 HXM (15/18) 94,7% - 228 100% - 44,893
HXM 2-4-61 99,7% - 3,013
HXM (12/18) 97,5% - 386 99,7% - 8,462
IH (12/18) 97,7% - 406 99,5% - 11,218
IH 2-4-62 100% - 2,766 HXM (15/18) 99,2% - 336 100% - 9,688
1. Lopez P & al. ICID 2012 & ESPID 2014 2. Aquino A & al. Vaccine 2012 3. Madhi S & al. PIDJ 2011
4. Madhi S & al. PIDJ 2013 5. Ceyhan M & al. ACPID 2010 6. Kosalaraska P & al. Int JID 2011
7. Lalwani S & al. PEDICON 2016 8. Vesikari T & al. ESPID 2015 9. Vesikari T & al. ESPID 2015 and 2016
10. Prymula R & al. ESPID 2016 11. Tregnaghi MW & al. PIDJ 2011 12. Lanata C & al. Vaccine & Vaccinations 2012

24. HepB immunization and use of hexavalent vaccines
The use of Hep-B containing combination vaccines in the first year
of life primary series offers below possibility:
●To adopt Hep B immunization regimen by using an hexa-only infant
primary series regimen
●Lead to a “0” (birth) + 3 +/- 1 (second year of life) regimen: “birth + 3 +
1” or “birth + 3 + 0”

25. Recommendations
WHO
IAP

26. Unique Features

27. Presentations
HEXAXIM® is available as FULLY LIQUID:30
● Needleless pre-filled syringes (box of 1 and 10) with two needle
lengths for optimal flexibility (16 mm 25G, 25 mm 23G)
• With double detachable labels for easy documentation
[30] Sanofi Pasteur. HEXAXIM®. Summary of Product Characteristics

28. Registered in more than 100 countries

29. Technological innovation

30. THANK YOU
docgaurav@gmail.com
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Acknowledgement: Dr Sujatha Shetty,
Sanofi Pasteur
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