The new kid on the blockHexavalent Vaccines!

Dr Gaurav Gupta,Pediatrician,

Mohali (Chandigarh)RajPedicon - Nov, 2016

Conflict of Interest

• Received grants from various vaccine manufacturers including – Sanofi Pasteur– GSK– Abbott– Novartis

WIIFY

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

What I won’t be talking about?

• aP versus wP• Components• Pricing

Combination Vaccines – Why?

• Simplified Immunization Schedule• Less injections – Complications• Better Compliance• Lesser administration time/ costs

Combination vaccines – Why not?

• Technically difficult• Expensive

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

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

Efficacy

• As compared to other aP vaccines• As compared to wP vaccines, specifically

against Pertussis

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®

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 similarto 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)

Sero

prot

ectio

n/Se

roco

nver

sion

rate

s (%

)

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 10094

8393

58

10093

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)

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 similarto that of PENTAXIM® co-administered with standalone hepatitis B vaccine

Sero

prot

ectio

n/Se

roco

nver

sion

rate

s (%

)

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 10092 93 93 90

100 100 100 100 100 100 99 10095 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®

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

Safety

• Safety as compared to wP vaccines

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

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)

Pain Red Swell A Fever Vom Crying Somnol Anor Irr0

20

40

60

80

100

The reactogenicity of HEXAXIM® is consistently lower than that ofwP-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 10Rea

ctio

n in

cide

nce

(%)

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 Gr3Pain Redness Swelling Fever Vomiting Crying Somnolence Anorexia Irritability

Tolerability Vs. wP-based combination vaccines

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

Indian Data

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 LalwaniDate : 23 January 2016

Venue : PEDICON – Hyderabad

WHO Universal Trial Number (UTN): U1111-1127-6936

Immunogenicity (Primary objective): % Seroprotection and Vaccine Response one month after 3 doses

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)

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

80.00%

90.00%

100.00% 99% 100%94%

99% 100% 100% 100% 100% 100%

20

Safety: Solicited reactions from D0 to D7, any grade, after each injection (in %)

21

Tenderness Erythema Swelling0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

19.00%

4.60%10.30%

13.80%

3.40% 3.40%

11.90%

0.60%6.50%

Post Dose 1 Post Dose 2 Post Dose 3

Fever Vomiting Abnormal Crying

Drowsiness Loss of appetite

Irritability0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

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%

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

What Schedule works?

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 + 0HXM 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% - 24296,1% - 267 HXM (12) 90,1% - 76

91,4% - 9598,9% - 2,23098,9% - 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 + 0HXM 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 20114. Madhi S & al. PIDJ 2013 5. Ceyhan M & al. ACPID 2010 6. Kosalaraska P & al. Int JID 20117. Lalwani S & al. PEDICON 2016 8. Vesikari T & al. ESPID 2015 9. Vesikari T & al. ESPID 2015 and 201610. Prymula R & al. ESPID 2016 11. Tregnaghi MW & al. PIDJ 2011 12. Lanata C & al. Vaccine & Vaccinations 2012

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”

Recommendations

WHO

IAP

Unique Features

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

Registered in more than 100 countries

Technological innovation

THANK YOU

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Acknowledgement: Dr Sujatha Shetty, Sanofi Pasteur

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