Hui

Process scientist

China

A/Prof Michael Nissen

Director, Scientific Affairs-AP

Singapore

A sneak peek into the future of vaccines

GSK Asia HQ- Singapore: Artistic impression

Employee of GlaxoSmithKline Vaccines& hold stock on LSTE

Adjunct Professor at Children’s Health Research Centre, University of QLD, Australia

2

Parasitic

Malaria

Viral

HIV

Ebola

RSV

Hepatitis C

Herpes zoster

GSK’s vaccine development pipeline has the potential to

help reduce the burden of many communicable diseases1,2

1. GSK. Vaccines. http://www.gsk.com/en-gb/about-us/what-we-do/vaccines/ (accessed February 2017); 2. GSK, 2016. Product pipeline – March 2016. http://www.gsk.com/en-

gb/investors/product-pipeline/ (accessed March 2017)

COPD, chronic obstructive pulmonary disease; HIV, human immunodeficiency virus; RSV, respiratory syncytial virus; TB, tuberculosis

Bacterial

TB

Group B Streptococcus

COPD

Meningococcal disease

Shigellosis

Pneumococcal disease

Poverty

Maternal

Paediatric

Therapeutic

Older

adults

Chronic

Emerging

disease

Adolescent

Drivers of vaccine

development:

$

$

$

$

$

GSK is developing innovative vaccines to help prevent

diseases

1. Ledgerwood JE et al. N Engl J Med 2017;376:928–938; 2. Dellagostin OA et al. Int J Mol Sci 2017;18:158; 3. Gerke C et al. PLoS ONE 2015;10:e0134478; 4. Di Pasquale A et al.

Vaccines 2015;3:320–343; 5. GSK. Vaccines. http://www.gsk.com/en-gb/about-us/what-we-do/vaccines/ (accessed March 2017); 6. GSK. Our vaccines. http://www.gsk.com/en-

gb/products/our-vaccines/#tab-2 (accessed March 2017); 7. Morrison C. Nat Rev Drug Discov 2016;15:521–522. 8. Feldman MF et al. PNAS 2005; 102(8): 3016-3021

Innovative technologies Vaccines for all5,6

Viral vectors1,4

Generalised

modules of

membrane antigens3

GSK Adjuvant

System4

Reverse

vaccinology2

Maternal

immunisation

Infants

Older adults

Paediatrics

Travellers

Adults

Adolescents

Self-amplifying

mRNA (SAM) 7Occupational health, e.g.

HCW*, military

*HCW = healthcare worker

Bioconjugation 8

Bexsero®

Meningococcal Group B Vaccine (rDNA, component, adsorbed)

Bexsero is a registered trademark of the

GlaxoSmithKline group of companies.

GlaxoSmithKline Biologicals S.A., Rixensart, Belgium

Prepared June 2016; VGBU/BEX/0005/16(1)

Bexsero is not registered or available in New Zealand

Neisseria meningitidis are classified into serogroups according

to the immunologic reactivity of their capsular polysaccharides1

– The polysaccharide capsule is key in determining virulence2

– Twelve serogroups have been identified based on the structure of their

polysaccharide capsule – only six (A, B, C, W, X and Y) cause invasive

meningococcal disease2,3

61. Rosenstein NE et al. N Engl J Med 2001;344:1378–1388; 2. Harrison OB et al. Emerg Infect Dis 2013;19:566–573; 3. WHO. Meningococcal meningitis fact sheet No. 141,

2015. http://www.who.int/mediacentre/factsheets/fs141/en (accessed November 2016). Images are © Hurd Studios, 2012 and courtesy of GlaxoSmithKline

Polysaccharide

capsule (serogroup)

PilusLipooligosaccharide

Cytoplasmic membrane proteins

Incidence of Invasive Meningococcal Disease (IMD) by Age

IMD, invasive meningococcal disease.

Total IMD cases, N=3436 (reported cases for which age information was provided, excluding aggregated data); serogroup B IMD cases, N=2182.

*Countries: Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania,

Luxembourg (total IMD cases only), Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom.

European Centre for Disease Prevention and Control. Surveillance of invasive bacterial diseases in Europe, 2012. Stockholm: ECDC; 2015.

http://ecdc.europa.eu/en/publications/Publications/Surveillance%20of%20IBD%20in%20Europe%202012.pdf. Accessed 11Feb2016.

IMD

ca

se

s p

er

10

0,0

00

of th

e a

ge

gro

up

0

2

4

6

8

10

12

<1 1–4 5–14 15–24 25–44 45–64 ≥65Age (years)

Total IMD cases

Serogroup B IMD cases

– Incidence highest in infants and young children

– A second, smaller peak in incidence occurs in adolescents and young adults

Europe,* 2012

8

8%

26%

38%

26%

NEW ZEALAND(2013, n=57)13

Neisseria meningitidis serogroup distribution varies between

regions/countries*

Other serogroups, not groupable, not tested, or missed

EUROPE(2014, n=2873)6

57%14%7%

9%

13%

57%12%

17%

78%

2%

10%8% 2%

53%30%

9%

7% 2%

Chart Title

7%12%

3%

42%

36%

29%

65%

6%

CANADA(2006–2011, n=1174)1

COLOMBIA(2015, n=48)3 BRAZIL

(2015, n=357)4

SOUTH AFRICA(2014, n=193)10

TURKEY(2005–2012, n=333)7

YWB CA

17%

40%36%

5% 3%

4%

64%

26%

28%

26%

10%

36%USA†

(2014, n=53)2

†USA: 36% ‘other’ serogroups includes

serogroup W and non-groupable;

surveillance data only covers some

areas of the USA, representing ~43.5

million people2

Serogroup data is across all age groups

Percentages may not total 100 due to rounding

ARGENTINA(2014, n=149)5

23%

9%

32%

16%

20%

47%

1%

49%

3%

AFRICANMENINGITIS

BELT (2015, n=1763)9

JAPAN(2014, n=59)11

AUSTRALIA(2014, n=165)12

SAUDI

ARABIA(2002–2011,

n=115)8

*Serogroup distribution cannot be directly compared across countries due to variability in surveillance data available.

<Further details on surveillance data for each country are shown on next slide for use as back-up, if required>

25%

60%

11%

2% 2%

Figure adapted from: 1. Li YA et al. Can Commun Dis Rep 2014;40(9):160–171; 2. Active Bacterial Core surveillance (ABCs). Surveillance reports, Neisseria meningitidis, 2014. Centers for Disease Control and

Prevention website. http://www.cdc.gov/abcs/reports-findings/survreports/mening14.pdf (accessed November 2016); 3. Vigilancia por laboratorio Neisseria meningitidis (aislaminetos invasores) periodo 1987–2015.

Instituto Nacional de la Salud. Grupo de Microbiologia. 2016. http://www.ins.gov.co/tramites-y-servicios/examenes-de-inter%C3%A9s-en-salud-publica/Microbiologa/informe%20Web%20N%20meningitidis%202015.pdf

(accessed November 2016); 4. Ministry of Health / SVS – Notifiable Diseases Information System – SINAN Net. http://tabnet.datasus.gov.br/cgi/tabcgi.exe?sinannet/cnv/meninbr.def (accessed November 2016);

5. Servicio Bacteriología Clínica-Departamento Bacteriología-INEI-ANLIS Dr.C.G. Malbrán-ARGENTINA. SIREVA II. http://antimicrobianos.com.ar/ATB/wp-content/uploads/2015/09/Tablas-vigilancia-SIREVA-II-Nm-2014-

Argentina1.pdf (accessed November 2016). 6. ECDC. Surveillance Atlas, 1999–2014. http://atlas.ecdc.europa.eu/public/index.aspx?Instance=GeneralAtlas (accessed November 2016); 7. Ceyhan M et al. Hum Vaccin

Immunother 2014;10:2706–2712; 8. Memish Z et al. Euro Surveill 2013;18:pii=20581; 9. WHO. 2016. Wkly Epidemiol Rec 2016;91:209–216; 10. GERMS-SA Annual Report 2014. National Institute for Communicable

Diseases. http://www.nicd.ac.za/assets/files/GERMS-SA%20AR%202014.pdf (accessed November 2016); 11. Fukusumi M et al. Vaccine 2016;34:4068–4071; 12. Australian Meningococcal Surveillance

Programme annual report 2014. www.health.gov.au/internet/main/publishing.nsf/Content/cda-pubs-annlrpt-menganrep.htm (accessed November 2016); 13. Lopez L et al. The epidemiology of meningococcal

disease in New Zealand in 2013. Institute of Environmental Science and Research Ltd (ESR), 2014

9

9%

6%

5%

Outer membrane vesicle (OMV) vaccines

Immunogenic and proven effective for a

single homologous serogroup B strain4,5

Limited protection against heterologous

meningococcal serogroup B strains4,5

Serogroup B strains are highly diverse4,5

• >5000 sequence types identified6

• >600 PorA variants (the dominant antigen in

OMV)4

A conjugate vaccine for Men B?

Vaccines with a single subcapsular antigen component do not offer broad protection

against Men B disease

Capsular vaccines

Poorly immunogenic1,2

• Structural homology between the

B polysaccharide of the capsule

and human tissue1,2

N meningitidis bacterial capsule Outer membrane “blebs” of N meningitidis

Image from Devoe et al. 19737

1. Finne J, et al. J Immunol 1987;138:4402–4407

2. Wyle FA, et al. J Infect Dis 1972;126:514–522

3. Sadarangani M, et al. Lancet Infect Dis 2010;10:112–124

4. Tan LK, et al. N Engl J Med 2010;362:1511–1520

5. Girard MP, et al. Vaccine 2006;24:4692–4700

6. Devoe IW, et al. Journal Exp Med 1973;138:1156–1167

10

Bexsero contains 4 antigenic components

fHbp: factor H–

binding protein

• Binds factor H,

which enables bacterial

survival in the blood1,2

Class

5

PorA

Class

4

PorB

LPS

OMV*

NadA: neisserial

adhesin A

• Promotes adherence to

and invasion of human

epithelial cells3–5

• May be important for

colonization4

NHBA: neisseria heparin–

binding antigen

• Binds heparin, which may

promote bacterial survival

in the blood6

• Present in virtually all

strains6,7

NZ PorA P1.4: porin A

• Major OMV protein8

• Shown to induce strain-

specific bactericidal

response when used in

MeNZB OMV vaccine^,8

^Developed by Chiron Vaccines in

association with the Norwegian

Institute of Public Health.

OMV, outer membrane vesicle.

1. Madico G, et al. J Immunol. 2006;177:501-510

2. Schneider MC, et al. Nature. 2009;458:890-893

3. Comanducci M, et al. J Exp Med. 2002;195:1445-1454

4. Capecchi B, et al. Mol Microbiol. 2005;55:687-698

5. Mazzon C, et al. J Immunol. 2007;179:3904-3916

6. Serruto D, et al. Proc Natl Acad Sci U S A. 2010;107:3770-3775

7. Bambini S, et al. Vaccine. 2009;27:2794-2803

8. Martin DR, et al. Clin Vaccine Immunol. 2006;13:486-491

9. Vesikari T, et al. Lancet. 2013;381:825-835

10. Vogel U, et al. Lancet Infect Dis. 2013;13:416-425

Identified using a “reverse vaccinology” approach

Multiple antigens may provide synergistic killing,

improve strain coverage, and insure against mutations9,10

11

Infants and children 2 months to <2 years of age

• 5849 received at least 1 dose of Bexsero

• 3285 received booster dose in second year of life

2677 adolescents (≥11 years of age) and adults

Bexsero safety was evaluated in 13 studies

including 9 randomised controlled clinical trials

250 children 2 to 10 years of age

>9000 subjects received at least 1 dose of the vaccine.

Studies included subjects from 2 months of age

Clinical trial experience with Bexsero

1. Bexsero Product Information

Study in special populations: children and adolescents aged 2 to 17 years

• 40 with complement deficiency; 107 with asplenia or splenic dysfunction

• 85 age-matched healthy participants

12

Bexsero Licensed Immunisation Schedules

3 doses2–5 months

6–11 months

12–23 months

2–10 years

11+ years

≥1 mo 1 dose age 12–15 mo*

2 doses

≥2 mo

≥1 mo

1 dose in the 2nd year of life≥2 mo post primary series

1 dose 12–23 mo post primary series

Need not established

Age groupPrimary

immunisation

Interval between

primary dosesBooster

The use of this vaccine should be in accordance with official recommendations.

*In case of delay, the booster should not be given later than 24 months.

European Union

Bexsero® [summary of product characteristics]. 13

Bexsero Immune Response in Infants Following

Vaccination at 2-4-6-12 Months

Figure adapted and reprinted from The Lancet, Vol. 381, Vesikari T et al., Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal

serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomized trials, Pages 825-835, Copyright (2013),

with permission from Elsevier.

1. Vesikari T, et al. Lancet. 2013;381:825-835; 2. Bexsero® [summary of product characteristics].

†Blood drawn at 7 months, N=1149–1183.‡Blood drawn at 12 months, N=434–437.§Blood drawn at 13 months, N=421–424.ǁN=100.

3 41

33

100 100

8484

81

99

22

61

100 10095

98

0

20

40

60

80

100

% o

f su

bje

cts

with

ba

cte

ricid

al tite

rs ≥

1:5

fHbp NadA PorA P1.4 NHBAǁ

Pre-booster (12 mo)1,‡Baseline1,* Post-primary (7 mo)1,† Post-booster (13 mo)2,§

2-4-6-12 month schedule with routine vaccines

14

*Routine vaccines: PCV7 and DTaP-HBV-IPV/Hib.†N=238–248.‡Criteria not met for lower limit of the 95% confidence interval for difference in seroresponse ≥10%.

Blood drawn at 7 months.

Vesikari T, et al. Lancet. 2013;381:825-835.

Routine vaccines alone*,†Bexsero® plus routine vaccines*,†

100 100 98 95 94 95 88 97 98 99100 100 100 99 98 97 94 98 100 1000

20

40

60

80

100

Diphtheria Tetanus PT FHA PRN Polio 1 Polio 2 Polio 3 HBV PRP-Hib

Antigens

% ≥0.15

mcg/mL% ≥10

mIU/mL% ≥1:8% ≥0.1

IU/mL

% ≥0.1

IU/mL

–1%(–5, 2)

–5%‡

(–11, –1)

–1%(–4, 2)

–2%(–5, –1)

–4%(–8, –1)

–4%(–8, –1)

0%(–1, 2)

0%(–2, 2)

–2%(–5, –1)

–1%(–3, 1)

% Seroconversion

(% 4-fold increase)

% S

ero

resp

onse o

r

% s

ero

co

nve

rsio

n

Immunogenicity of Routine Infant Vaccines

Administered with BexseroRoutine vaccines given with or without Bexsero at 2, 4, and 6 months of age

15

Tolerability Profile for Bexsero in Clinical Trials

*Pneumococcal 7-valent conjugate vaccine, diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis, and Haemophilus influenzae type b vaccine.†Separate vaccinations can be considered when possible. Separate injection sites must be used if more than one vaccine is administered at the same time.

Bexsero® [summary of product characteristics].

Most common adverse reactions

Bexserogiven alone

Bexsero given with other vaccines*,†

Infants and children

(less than 2 y)

Tenderness and erythema at the injection site, fever,

and irritability

Frequency of fever was similar to that associated

with routine infant vaccines* administered during clinical

trials

Higher rate of fever and systemic reactions

(irritability, change in eating habits, sleepiness,

tenderness at the injection site)

Adolescents and adults

The most common adverse reactions were pain at the injection site, malaise, and headache; fever rates were similar for Bexsero® compared with placebo

17

Impact of Prophylactic Paracetamol on Fever

0

10

20

30

40

50

60

NPP PP* NPP PP* NPP PP*

% S

ub

jects

6 hours Day 2 Day 3

Time

Post–any dose*

(2-3-4 month schedule)

38.5°C to <39°C

39°C to <40°C

≥40°C

NPP, no prophylactic paracetamol (N=181–182); PP, with prophylactic paracetamol (N=181–182).

*Subjects received 1 dose of 10–15 mg/kg oral paracetamol before vaccination, followed by 2 additional doses of paracetamol

4–6 hours after vaccination. Routine vaccines: PCV7 and DTaP-HBV-IPV/Hib.

Figure adapted and reprinted from Hum Vaccin Immunother, Vol. 10, Prymula R, et al., A phase 2 randomized controlled trial of a multicomponent meningococcal serogroup B

vaccine (I), Pages 1993-2004, Copyright (2014), with permission of the publisher (Taylor & Francis Ltd, http://www.tandfonline.com).

When Bexsero is given concomitantly with routine infant vaccines

18

UK: National MenB vaccination programme8‒10

In 2015, Bexsero was introduced to help

protect against MenB disease in the UK8 –

~700,000 infants per year were targeted

for vaccination9,10^

Canada: Regional vaccination campaign in Quebec and University outbreak in Nova Scotia5‒7

Regional campaign in Saguenay–Lac-Saint-Jean, Quebec5,6

In 2014, 57,038 residents or those in education aged ≥2 months

to ≤20 years were targeted for Bexsero vaccination to help

protect against the high incidence of MenB disease in the

region. Between 5 May and 17 June 2014, 43,740 individuals

received the first dose

Outbreak at Acadia University, Nova Scotia7

In 2015, a two-dose MenB vaccination campaign with Bexsero

was introduced at Acadia University, Nova Scotia – 2967

individuals received the first dose in February to March 2015

and 987 participants were assessed in an online safety survey

following dose 1*Under IND protocol prior to US approval (January 2015)1,3

^Using a dosing schedule outside of the approved label

Summary of Bexsero real-world experience

USA: University outbreaks

Princeton University and University of California at

Santa Barbara1,2

In 2013, the FDA authorised vaccination campaigns with

Bexsero* in response to two university outbreaks;

surveillance data for 15,236 individuals vaccinated with

Bexsero have been reported1,3

Santa Clara4

In 2016, a two-dose vaccination campaign with Bexsero

was introduced – 4921 individuals received the first

dose in February 2016

1. Watson P and Turner D. Vaccine 2016;34:875–80; 2. NMA 2016. http://www.nmaus.org/disease-prevention-information/serogroup-b-meningococcal-disease/outbreaks/

(Accessed September 2016); 3. US FDA press release 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm431370.htm (Accessed September 2016);

4. Biswas HH et al. MMWR Morb Mortal Wkly Rep 2016;65:520–1; 5. INSPQ 2014 Interim report. https://www.inspq.qc.ca/pdf/publications/1902_SerogroupB_Meningococcal_Vaccine.pdf (Accessed September

2016); 6. CIUSSS 2015 Press release. http://santesaglac.com/medias/documents/communiques_presse/2015/COMMUNIQUE_meningoB__150415.pdf (Accessed September 2016);

7. Langley JM et al. Vaccine 2016;34:4046–9; 8. Ladhani SN et al. Arch Dis Child 2016;101:91–5; 9. ONS England and Wales 2014.

http://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/livebirths/bulletins/birthsummarytablesenglandandwales/2015-07-15 (Accessed September 2016); 10. NRS Scotland 2015.

http://www.nrscotland.gov.uk/news/2015/births-deaths-and-other-vital-events-preliminary-figures-for-2014-released (Accessed September 2016). Figure adapted from references 1–10

19

National vaccine

programme with the

entire UK birth cohort

Sophisticated

surveillance

Coverage:

1 dose = 95.5%

2 dose = 88.6%

2-dose effectiveness:

82.9% (24.1-95.2)

20

Summary

– Serogroup B disease affects mainly infants, is easily misdiagnosed, can kill within 24 hours

of onset, and may cause serious, lifelong disabilities despite appropriate medical treatment

– Bexsero is a novel meningococcal serogroup B vaccine for active immunisation against

invasive MenB disease

– Bexsero offers several schedule options that fit with routine vaccination visits and possible

catch-up programs

– In clinical trials, Bexsero has demonstrated a protective immune response in infants,

children, adolescents, and adults with or without routine vaccines

– Bexsero has a demonstrated safety profile based on an evaluation of >67,000 subjects

in clinical trials and postmarketing studies (from 2 months of age)

– Results from the UK, Canada and USA demonstrate real-world effectiveness of Bexsero*

21*Bexsero® is not expected to provide protection against all circulating meningococcal group B strains.

Herpes zoster (shingles)

and GSK’s adjuvanted

subunit vaccine candidate

(HZ/su)

©2017 GlaxoSmithKline. All rights reserved. GlaxoSmithKline Biologicals SA, Rixensart, Belgium

Date of Preparation: June 2017; Zinc job bag: VGBU/ZOS/0005/17

HZ/su is not registered or available in New Zealand

23*From American Academy of Pediatrics. Varicella-Zoster Virus Infections. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book©: 2015 Report of the Committee on Infectious

Diseases. Elk Grove Village, IL: American Academy of Pediatrics; 2015:846-860. Copyright © 2015. Reproduced with permission. HZ, herpes zoster; VZV, varicella zoster virus

HZ is caused by the reactivation of the dormant varicella

zoster virus1

1. Kimberlin DW, et al. New Engl J Med 2007;356:1338‒43; 2. Harpaz R, et al. MMWR Recomm Rep 2008;57:1‒30

Approximately 99.5% of adults ≥40 years of age show serologic evidence of VZV

infection, and one in three people develop shingles in their lifetime2

Primary infection:

varicella (chickenpox)1

© loflo6

9,

Dep

ositp

ho

tos,

Inc.

*see footnote

VZV becomes latent in

the sensory ganglia

nerves1

Thoracic

spinal

column

Chickenpox

lesion

Sensory

neurons

Zoster

lesions

Dorsal-root

ganglion

(latent virus)

Ima

ge

so

urc

e S

hu

tte

rsto

ck

Reactivation of infection:

HZ (shingles)1

Ima

ge

so

urc

e S

hu

tte

rsto

ck

24

The natural course of HZ is made of an acute phase

often followed by chronic complications

1. Harpaz R, et al. MMWR Recomm Rep 2008;57:1‒30; 2. Kawai K, et al. BMJ Open 2014;4:e004883; 3. Opstelten W, et al. Fam Pract 2002;19:471‒5; 4. Dworkin RH, et

al. J Pain 2008;9:S37‒4; 5. Dworkin RH, et al. Clin Infect Dis 2007;44:S1‒26; 6. Nagel MA and Gilden D. Curr Neurol Meurosci rep 2015:15:16; 7. Yawn BP, et al. Mayo

Clin Proc 2011;86:88‒93

Headache,

fever,

myalgia1

Localised rash,

associated

acute pain1

Prodrome Acute (2-4 weeks)1

Recurrence

rate

~5%7

HZO, herpes zoster ophthalmicus; PHN, postherpetic neuralgia

Others: stroke, bacterial superinfection, hearing loss,

palsy, scarring, nerve cell/fiber damage1,5,6

Chronic (1‒ 3 months)3 years

5‒30% of

patients2

PHN1,2,4

HZO1,2

ima

ge

so

urc

e: iS

tock P

ho

to

25

The risk of HZ increases with the decline in

immune system function1

Patients on immunosuppressant drugs,

with immunodeficient conditions or

receiving transplants

Compromised immune system

(immunocompromised)1

Older adults (≥50 years of age)

Aging immune system

(immunosenescence)1

1. Harpaz R, et al. MMWR Recomm Rep 2008;57:1‒30

Image source Shutterstock Image source Getty images

26

HZ/su vaccine compositionHZ/su: for the prevention of HZ and HZ-related complications, such as PHN, in adults ≥50 years of age

HZ/su vaccineNon live

Adjuvant systemAS01B: QS-21* and MPL - 50 µg each

AntigengE - 50 µg

Glycoprotein spikes

Lipid envelope

DNA

Nucleocapsid

Tegument

MPL QS-21 Saponin

Ad

ap

tatio

n o

f a

Sh

utt

ers

tock im

ag

e

*QS-21 adjuvant licensed from Antigenics Inc, a wholly owned subsidiary of Agenus Inc.

a Delaware USA corporation; gE, glycoprotein; MPL, 3-O-desacyl-4’-monophosphoryl

lipid A; QS-21, Quillaja saponaria Molina, fraction 21

Ima

ge

of tr

ee

by

Fra

nz

Eu

ge

n K

öh

ler,

Kö

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r's

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ina

l-P

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n

1. Lal H et al., N Eng J Med 2015, 372: 2087-96; 2. Cunnigham A et al, N Eng J Med 2016,75:1019-32

27

HZ/su pivotal phase III programme: ZOE-50 and ZOE-701,2

New England Journal of Medicine, 2015, 2016

ZOE-50 and ZOE-70 studies conducted at the same sites

Subjects ≥70 years of age were randomly assigned to ZOE-50 or ZOE-70

Study design

and objectivesZOE-501

(Zoster-006)

ZOE-702

(Zoster-022)

Study designRandomised, observer-blind, placebo-controlled, multicentre,

multinational (North America, Europe, Latin America, Asia-Pacific)

Schedule 2 doses administered 2 months apart

Primary objectivesVEHZ in subjects

≥50 years of age

VEHZ in subjects

≥70 years of age

Primary objectives

(pooled analysis)

VEPHN in individuals ≥70 years of age

VEHZ efficacy in individuals ≥70 years of age

Actual enrollment 16160 14816

1.Lal H, et al. N Engl J Med 2015;372:2087‒96; 2. Cunningham AL, et al. N Engl J Med 2016;75:1019‒32

PHN, postherpetic neuralgia; VE, vaccine efficacy

Vaccine efficacy against HZ in subjects

50 years and older

†p-value for all efficacy comparisons with placebo <0.001*Excludes subjects not receiving Dose 2 or who developed HZ within 1 month after Dose 2^Number per 1,000 person-years

Age range

(years)

HZ/su

N=7,344

Placebo

N=7,415

VE (95% CI)†HZ cases Rate of HZ^ HZ cases Rate of HZ^

Overall (≥50) 6 0.3 210 9.197.2

(93.7-99.0)

50−59 3 0.3 87 7.896.6

(89.6-99.3)

60−69 2 0.3 75 10.897.4

(90.1-99.7)

≥70 1 0.2 48 9.497.9

(87.9-100)

Secondary objectivePrimary objective

ZOE-50 mTVC*

28Lal H,Cunningham A, Godeaux O, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. NEJM 2015;372:2087-96

CI, confidence interval; HZ/su, herpes zoster subunit vaccine; mTVC, modified total vaccinated cohort; VE, vaccine efficacy

Age independent

efficacy

29

High efficacy for HZ/su sustained with minimal decline

up to 4 years post initial vaccination (ZOE-70)*

Years†

HZ/su Placebo

VEHZ

(95% CI)‡

HZ cases

(n)

Rate(cases per 1000

person-years)

HZ cases

(n)

Rate(cases per 1000

person-years)

Year 1 2 (8250) 0.2 83 (8346) 10.1 97.6%(90.9, 99.8)

Year 2 7 (8039) 0.9 87 (8024) 11.1 92.0%(82.8, 96.9)

Year 3 9 (7736) 1.2 58 (7661) 7.7 84.7%(69.0, 93.4)

Year 4 7 (7426) 1.0 56 (7267) 8.2 87.9%(73.3, 95.4)

Va

cc

ine

eff

ica

cy b

y

ye

ar

po

st

va

cc

ina

tio

n

*Subjects followed-up for a mean of 3.7 years at the time of this publication†Year 1:30‒395 days after the second vaccination; Year 2: 396‒760 days after the second vaccination; Year 3: 761‒1125 days after

the second vaccination; Year 4: >1125 after the second vaccination to the last contact date. n=number of subjects within each age

group‡p<0.001 for all comparisons

CI, confidence interval; HZ/su, herpes zoster subunit vaccine; VE, vaccine efficacy

1. Cunningham AL, et al. N Engl J Med 2016;75:1019‒32

30

HZ/su greatly reduced HZ complications, such as PHN,

among all groups ≥50 years of age*1,2

PHN defined as HZ-associated pain rated as ≥3 on a 0‒10 scale, occurring or persisting for at least 90 days following the onset of

rash using Zoster Brief Pain Inventory questionnaire. Pooled data from ZOE-50 (subjects ≥50 years of age) and ZOE-70 (subjects

≥70 years of age)

*All subjects randomised in the study who received a second dose of the vaccine. Final analysis data cut-off date: July 1, 2014;

mean follow-up 3.8 years; †p<0.001 for both comparisons

CI, confidence interval; HZ/su, herpes zoster subunit vaccine ; PHN, postherpetic neuralgia; VE, vaccine efficacy

Pre-specified, pooled analyses from ZOE-50 and ZOE-70

1. Cunningham AL, et al. N Engl J Med 2016;75:1019‒32; 2. GlaxoSmithKline Data on File for the Investigational Herpes Zoster subunit vaccine Candidate - VGBU/ZOS/0005/17 –

29/JUNE/2017

Age,

years

HZ/su Placebo

VEHZ

(95% CI)†

PHN cases

(n)

Rate(cases per

1000

person-years)

PHN cases

(n)

Rate(cases per

1000

person-years)

≥50 4 (13881) 0.1 36 (8346) 1.2 91.2%(75.9, 97.7)

≥70 4 (8250) 0.1 46 (14035) 0.9 88.8%(68.7, 97.1)

• In a post-hoc pooled analysis from ZOE-50 and ZOE-70, HZ/su also reduced non-PHN

complications (HZ vasculitis, stroke, disseminated, ophthalmic, neurological and visceral disease)2

o VE in subjects ≥50 years of age: 93.7% (95% CI 59.5, 99.9)

o VE in subjects ≥70 years of age: 91.6% (95% CI 43.4, 99.8)

31

Local adverse reactions to HZ/su were transient;

(mean duration 2‒3 days)1,2

Solicited local symptoms reported during 7 days post vaccination:

any grade overall by subject

0

20

40

60

80

100

Pain Redness Swelling

HZ/su ZOE-50(n=4382)

Placebo ZOE-50(n=4377)

HZ/su ZOE-70(n=505)

Placebo ZOE-70(n=505)

ZOE-50: Overall median duration of 3 days for pain, redness and swelling3

ZOE-70: Overall median duration of 2 days for pain; 3 days for redness and swelling2

Pe

rce

nta

ge

(%

)

n= Number of subjects with at least 1 documented dose

%= Percentage of subjects reporting the symptom at least once when the intensity is maximum

1. Lal H, et al. N Engl J Med 2015;372:2087‒96; 2.Cunningham AL, et al. N Engl J Med 2016;75:1019‒32; 3. Colindres R. Safety summary of investigational vaccine: SHINGRIX

(HZ/su). ACIP February 22, 2017 [last accessed 2017 June]. Available from: www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-02/zoster-02-gsk.pdf

32

Systemic adverse reactions to HZ/su were transient

(mean duration 1‒2 days)1,2

0

20

40

60

80

100

Fatigue Fever (≥37.5°C/≥99.5°F)

GI* Headache Myalgia Shivering

HZ/su ZOE-50(n=4375)

Placebo ZOE-50(n=4378)

HZ/su ZOE-70(n=504)

Placebo ZOE-70(n=505)

Solicited systemic symptoms reported during 7 days post vaccination:

any grade overall by subject

Pe

rce

nta

ge

(%

)

ZOE-50: Median duration of 2 days for fatigue, GI, HA and myalgia; 1 day for fever and shivering3

ZOE-70: Median duration of 2 days for fatigue, GI, HA myalgia and fever; 1 day for shivering2

*GI symptoms included nausea, vomiting, diarrhoea, and/or abdominal pain

GI, gastrointestinal; HA, headache; n= Number of subjects with at least 1 documented dose; % = Percentage of subjects reporting

the symptom at least once when the intensity is maximum

1. Lal H, et al. N Engl J Med 2015;372:2087‒96; 2.Cunningham AL, et al. N Engl J Med 2016;75:1019‒32; 3. Colindres R. Safety summary of investigational vaccine: SHINGRIX

(HZ/su). ACIP February 22, 2017 [last accessed 2017 June]. Available from: www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-02/zoster-02-gsk.pdf

33

HZ/su provided efficacy across all age groups ≥50 years of

age with an acceptable safety and tolerability profile

1.Lal H, et al. N Engl J Med 2015;372:2087‒96; 2. Cunningham AL, et al. N Engl J Med 2016;75:1019‒32; 3. Colindres R. Safety summary of investigational vaccine: SHINGRIX (HZ/su). ACIP February 22, 2017 [last accessed 2017 June].

Available from: www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-02/zoster-02-gsk.pdf ; 4. Study 113077 clinical study summary; 2016 [last accessed 2017, June]. Available from: www.gsk-clinicalstudyregister.com/study/113077#rs;

5. GlaxoSmithKline Data on File for the Investigational Herpes Zoster subunit vaccine Candidate - VGBU/ZOS/0005/17 – 29/JUNE/2017; ; 6. Study 110390 clinical study summary; 2016 [last accessed 2017 June]. Available from: www.gsk-

clinicalstudyregister.com/study/110390#rs

>90% efficacy shown in all age groups ‒from 50 to over 80 years of age

(pooled data from 2 pivotal phase 3 trials)1,2

There was no significant decline in efficacy during an ongoing follow-up period

(median 4.4 years),2 and immunogenicity was maintained for at least 9 years3

HZ/su eliminated almost all occurrences of PHN and non-PHN complications*2,4,5

Adverse reactions were mostly transient and of mild-to-moderate intensity, with a

median duration of 3 days2,3,4,6

– z

– z

– z

Efficacy

Safety

– z

*HZ vaculitis, disseminated disease, ophthalmic disease, neurological disease visceral disease, stroke

Q&A

Prescribing Information— Bexsero Meningococcal Group B Vaccine

(rDNA, Component, Adsorbed)

Active ingredients:

One dose (0.5 ml) contains:

Recombinant Neisseria meningitidis group B NHBA fusion protein - 50 µg;

Recombinant Neisseria meningitidis group B NadA protein - 50 µg;

Recombinant Neisseria meningitidis group B fHbp fusion protein - 50 µg;

Outer membrane vesicles (OMV) from Neisseria meningitidis group B strain NZ98/254 measured as amount of total protein

containing the PorA P1.4 - 25 µg

Indications: Bexsero is indicated for active immunization of individuals from 2 months of age and older against invasive

meningococcal disease caused by Neisseria meningitidis group B.*

Method of administration: The vaccine is given by deep intramuscular injection.

Dosage information:

From 2 to 5 months: Three doses each of 0.5 ml, with first dose given at 2 months of age, with no less than 2-month interval

between primary doses and a booster dose between 12 and 15 months. Unvaccinated infants, 6 months to 11 months: Two

doses each of 0.5 ml, with no less than 2-month interval and a booster dose in the second year of life, respecting at least a 2-

month interval between primary doses and booster dose. Unvaccinated children, 12 months to 23 months: Two doses each

of 0.5 ml, with no less than 2-month interval between the primary doses and a booster dose, respecting an interval of 12 to

23 months between primary doses and booster dose. Children, 2 years to 10 years: Two doses each of 0.5 ml, with no less

than 2-month interval between the primary doses. Adolescents (from 11 years of age) and adults: Two doses each of 0.5 ml,

with no less than 1-month interval between the primary doses. A booster dose was not established in children from 2 to 10

years old, adolescents and adults.

*Bexsero is not expected to provide protection against all circulating meningococcal group B strains.

Bexsero is a registered trademark of the GlaxoSmithKline group of companies.

Prescribing Information— Bexsero Meningococcal Group B Vaccine

(rDNA, Component, Adsorbed)

Adverse events: See the local label for details.

Infants and children (up to 10 years): Very common: Eating disorders, sleepiness, unusual crying, diarrhea, vomiting (uncommon after booster), rash (children aged

12 to 23 months, uncommon after booster), fever (≥38°C), erythema, swelling, induration and tenderness at the injection site (including severe injection site

tenderness, defined as crying when injected limb is moved), irritability; Common: Rash (children aged between 12 and 23 months); Uncommon: Seizures (including

febrile seizures), pallor (rare after booster); Rare: Kawasaki syndrome, urticaria. Adolescents (from 11 years of age) and adults: Very common: headache, nausea,

swelling, induration, erythema, and pain at the injection site (including severe injection site pain, defined as unable to perform normal daily activity), malaise, myalgia,

arthralgia.

Contraindications:

Hypersensitivity to the active substances or to any of the excipients listed in the formulation.

Interaction with other medicinal products:

The safety profile of the coadministered routine vaccines were unaffected by concomitant administration of Meningococcal group B Vaccine (rDNA, component,

adsorbed), except for an increased risk of fever, tenderness at the injection site, change in eating habits, and irritability. The coadministration of whole-cell pertussis

with Meningococcal group B vaccine (rDNA, component, adsorbed) has not been studied and therefore is not recommended. When coadministered with other

vaccine, the Meningococcal group B Vaccine (rDNA, component, adsorbed) must be applied in a distinct injection site.

Precautions and warnings:

Administration of Meningococcal group B Vaccine (rDNA, component, adsorbed) should be postponed in subjects suffering from acute severe febrile illness. The

presence of a minor infection is not a contraindication for immunization. The vaccine should under no circumstances be injected via intravascular. Appropriate medical

treatment and supervision should always be available in case of anaphylactic event following administration of the vaccine. Reactions related to anxiety including

vasovagal reactions (syncope), hyperventilation, or stress-related reactions can occur in association with vaccination as a psychogenic response to the needle

injection. The vaccine should not be administered in patients with thrombocytopenia or bleeding disorder that may contraindicate intramuscular injection, unless the

potential benefit clearly outweighs the risk of administration. As with any vaccine, Meningococcal group B Vaccine (rDNA, component, adsorbed) may not fully protect

all of those who are vaccinated. It is not expected that the vaccine provides protection against all meningococcal strains circulating in group B.

Medicinal product subject to medical prescription.

Cost: Please contact the local Key account manager from GSK for pricing information if applicable.

Agency Product Number: EMEA/H/C/002333

Marketing Authorization Holder:

Bexsero is a registered trademark of the GlaxoSmithKline group of companies.

Succinct Safety Statement— Bexsero Meningococcal Group B Vaccine

(rDNA, Component, Adsorbed)

Side effects:

Infants and children (up to 10 years): Very common: Eating disorders, sleepiness, unusual crying, diarrhea, vomiting (uncommon after booster),

rash (children aged 12 to 23 months, uncommon after booster), fever (≥38°C), erythema, swelling, induration and tenderness at the injection site

(including severe injection site tenderness, defined as crying when injected limb is moved), irritability; Common: Rash (children aged between 12 and

23 months); Uncommon: Seizures (including febrile seizures), pallor (rare after booster); Rare: Kawasaki syndrome, urticaria. Adolescents (from 11

years of age) and adults: Very common: Headache, nausea, swelling, induration, erythema, and pain at the injection site (including severe injection

site pain, defined as unable to perform normal daily activity), malaise, myalgia, arthralgia.

Interactions:

The safety profile of the coadministered routine vaccines were unaffected by concomitant administration of Meningococcal group B Vaccine (rDNA,

component, adsorbed), except for an increased risk of fever, tenderness at the injection site, change in eating habits, and irritability. The

coadministration of whole-cell pertussis with Meningococcal group B vaccine (rDNA, component, adsorbed) has not been studied and therefore is not

recommended. When coadministered with other vaccine, the Meningococcal group B Vaccine (rDNA, component, adsorbed) must be applied in a

distinct injection site.

Contraindications:

Hypersensitivity to the active substances or to any of the excipients listed in the formulation.

Precautions:

Administration of Meningococcal group B Vaccine (rDNA, component, adsorbed) should be postponed in subjects suffering from acute severe febrile

illness. The presence of a minor infection is not a contraindication for immunization. The vaccine should under no circumstances be injected via

intravascular. Appropriate medical treatment and supervision should always be available in case of anaphylactic event following administration of the

vaccine. Reactions related to anxiety including vasovagal reactions (syncope), hyperventilation, or stress-related reactions can occur in association

with vaccination as a psychogenic response to the needle injection. The vaccine should not be administered in patients with thrombocytopenia or

bleeding disorder that may contraindicate intramuscular injection, unless the potential benefit clearly outweighs the risk of administration. As with any

vaccine, Meningococcal group B Vaccine (rDNA, component, adsorbed) may not fully protect all of those who are vaccinated. It is not expected that

the vaccine provides protection against all meningococcal strains circulating in group B.

Bexsero is a registered trademark of the GlaxoSmithKline group of companies.