Helping protect against Meningococcal B -A new vaccine for New Zealand

A/Prof Michael NissenDirector, Scientific Affairs and Public HealthGSK VaccinesIntercontinental Region

Disclaimer

GlaxoSmithKline (GSK) can only recommend the use of treatments in accordance with the approved Data Sheet.

Please review the Data Sheet before prescribing. The Bexsero Data Sheet is available at: http://www.medsafe.govt.nz/profs/Datasheet/datasheet.htm

Invasive Meningococcal Disease (IMD)

Invasive Meningococcal Disease (IMD) causes significant morbidity and mortality

• Significant morbidity and mortality despite early diagnosis and appropriate medical treatment

• ~10% of cases are fatal1,2

• Up to 1 in 5 survivors of IMD (all serogroups) have permanent sequelae1,2

• Child survivors may experience major sequelae, including limb amputations, seizures and hearing loss3

• More than 30% of child survivors experience other deficits such as psychological disorders, deficits of memory, digit amputations and unilateral hearing loss3

1. Meningococcal meningitis factsheet No 141. World Health Organization website. http://www.who.int/mediacentre/factsheets/fs141/en/2. Rosenstein NE, et al. N Engl J Med. 2001; 344:1378-1388 3. Viner RM, et al. Lancet Neurol. 2012; 11:774-783.

Top image: Courtesy of Centers for Disease Control and Prevention and Dr. Gust. Bottom image: Courtesy of Meningitis Research Foundation UK. Available at

www.meningitis.org

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Notes: Meningococcal disease and Hib meningitis: despite appropriate antimicrobial therapy; paralytic polio: in children; 1918 pandemic flu: in young adults; varicella: in children and adolescents; A/H1N1 2009 flu: worldwide; measles: US, 1985‒1992; rotavirus: US general population; pertussis: infants <6 months of age, US, 2001–2003.

Estim

ated

cas

e fa

talit

y ra

te (%

)

Meningococcal disease1

Paralytic polio1

Pneumococcal pneumonia1

Diphtheria1

Hib meningitis1

1918 pandemic flu2

By infectious disease

1. Centers for Disease Control and Prevention (CDC). Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed. Atkinson W, et al, eds. Washington, DC: Public Health Foundation; 2012. http://www.cdc.gov/vaccines/pubs/pinkbook/index.html#chapters; 2. Taubenberger JK, et al. Emerg Infect Dis. 2006;12:15-22; 3. Pandemic H1N1 2009 Overview. CIDRAP website. http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/biofacts/h1n1_panview.html; 4. Gerba CP, et al. Wat Res. 1996:30;2929-2940; 5. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep. 2005;54:1283-1286.

IMD = invasive meningococcal disease VPDs = vaccine preventable diseases

IMD is associated with a higher case fatality rate compared with other VPDs

~ 13 hours - Median time to first hospitalisation*

• Neck pain and stiffness• Hemorrhagic rash• Floppy muscle tone#

• Bulging fontanelle*• Photophobia• Confusion and delirium^

• Seizure• Loss of consciousness

~8 hrs – Median time to first GP consultation*

• Cold hands and feet• Abnormal skin colour• Breathing difficulty• Increased thirst• Diarrhoea

Early misdiagnosis is commonMedical intervention often does not occur until late

1. Thompson MJ, et al. Lancet 2006; 367:397–4032. van Deuren M, et al. Clin Microbiol Rev 2000: 13:144–166

0-7 HOURS

NON SPECIFIC SYMPTOMS

• Fever• Irritability• Nausea or vomiting• Poor appetite or feeding• Drowsiness• Headache^

• Sore throat • Thirst• Leg pain• General aches

13-24 HOURSPOTENTIALLY

LETHALMost progressed from non-specific initial symptoms to

close to death within 24 hours

8 – 12 HOURS ^in children > 1 year

*in infants <1 year

*in infants <1 year#in children < 5 years^in children > 1 year

24HOURS

Meningococcal disease is caused by the bacterium Neisseria meningitidis1

1. Australian Technical Advisory Group on Immunisation (ATAGI). The Australian Immunisation Handbook 10th Edition (2016 update) . Canberra: Australian Government Department of Health, 2016 [Accessed February 2017]

2. Meningococcal meningitis factsheet No 141. World Health Organization website. http://www.who.int/mediacentre/factsheets/fs141/en/[Accessed February 2017]

3. ESR Notifiable Diseases in New Zealand Annual Report: https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualSurv/2016/2016AnnualNDReportFinal.pdf [Accessed: Jan 2018]

4. Rosenstein NE, et al. N Engl J Med. 2001; 344:1378-1388

Cross-section of N. meningitidis bacterial cell wall (adapted from Rosenstein et al)4

• Meningococci are classified into serogroups, determined by the components of the polysaccharide capsule1

• Globally, 6 serogroups most commonly cause disease2

• In New Zealand, serotypes B and C cause the majority of IMD3. In 2016, 70% of meningococcal cases that could be typed were group B

A B C W X Y

B C

Transmission & Infection

• From person to person through contact with respiratory or throat secretions from an infected person1

• Close and prolonged contact facilitates the spread of the disease, e.g. kissing, sneezing or coughing on someone, living in close quarters (dormitory, sharing eating or drinking utensils)2

• The bacterium attach to the surface of the nasopharynx and multiply3

• This can lead to transient carriage (asymptomatic) or result in invasive disease

N. meningitidis is transmitted via aerosol droplets or through direct contact

1. NZ Ministry of Health Immunisation Handbook: https://www.health.govt.nz/system/files/documents/publications/immunisation-handbook-2017-may17-v3.pdf [Accessed Jan 2018]

2. World Health Organization (WHO). Fact Sheet: Meningococcal meningitis. Fact sheet No. 141. Updated November 2015. http://www.who.int/mediacentre/factsheets/fs141/en/ [Accessed February 2017]

3. Rosenstein NE, et al. N Engl J Med. 2001; 344:1378-1388

Meningococcal Disease in New Zealand

NZ has a high rate of IMD compared with other countries worldwide*

Country Year Notification rate Source

New Zealand 2016 1.6ESR Surveillance Report Notifiable Disease in New Zealand 2016 https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualSurv/2016/2016AnnualNDReportFinal.pdf

Australia 2017 1.6

Australian Government Department of Health Invasive meningococcal disease National surveillance report 31 December 2017https://www.health.gov.au/internet/main/publishing.nsf/Content/5FEABC4B495BDEC1CA25807D001327FA/$File/31-Mar18-IMD-Surveillance-report.pdf

US 2016 0.12CDC Enhanced Meningococcal Disease Surveillance report, 2016https://www.cdc.gov/meningococcal/downloads/NCIRD-EMS-Report.pdf

England 2016–2017 1.0

Public Health England Invasive meningococcal disease in England: annual laboratory confirmed reports for epidemiological year 2016 to 2017 https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/655626/hrp3817_IMD.pdf

Canada 2011 0.51

CCDR: Vol 40-9, May 1, 2014 https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2014-40/ccdr-volume-40-9-may-1-2014/ccdr-volume-40-9-may-1-2014-1.html

10

*Some countries have an IMD vaccination programme in place

IMD incidence in NZ is unpredictable and can change rapidly

1. ESR Notifiable Diseases in New Zealand Annual Report: https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualSurv/2016/2016AnnualNDReportFinal.pdf [Accessed: Jan 2018]

Serogroup B causes the majority of IMD in New ZealandIMD strain distribution by year 2007-2017 in New Zealand, lab-confirmed cases

1. The Institute of Environmental Science and Research, Meningococcal disease epidemiology data request. GSK. 2018.

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2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

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Year

B C E W Y NG Other

In 2016, 70% of meningococcal cases that could be typed were

serogroup B

IMD disproportionately affects the <1 age group in NZ

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<1 1-4 5-9 14-19 15-19 20-29 30-39 40-49 50-59 60-69 >70

Not

ifica

tion

rate

per

100

,000

Age Group

Total IMD Meningococcal B

Infants have the highest IMD

notification rate of 18.6 per 100,0002

1. The Institute of Environmental Science and Research, Meningococcal disease epidemiology data request. GSK. 2017.2. ESR Notifiable Diseases in New Zealand Annual Report:

https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualSurv/2016/2016AnnualNDReportFinal.pdf [Accessed: May 2018]

Rate per 100,000 of total IMD and Meningococcal B disease in New Zealand in 2016

* * *

* Total IMD rate not

calculated

Infants <1 year are most vulnerable to meningococcal infection

1. ESR Notifiable Diseases in New Zealand Annual Report: https://surv.esr.cri.nz/PDF_surveillance/AnnualRpt/AnnualSurv/2016/2016AnnualNDReportFinal.pdf [Accessed: May 2018]

2. The Institute of Environmental Science and Research, Meningococcal disease epidemiology data request. GSK. 2017.3. Sadarangani et al Clinical Infectious Diseases 2015; 60:e27-35. 4. Edge et al, Journal of Infection 2016; 73:427-436.

Infants <1 year have the highest notification rate of invasive meningococcal disease, over 10 times the national average in 20161

Meningococcal B is the most common cause of IMD in infants < 1 year2

While the case fatality rate is highest in older populations (>60 years), infants (<1 year) and young children (1-4 years) experience the highest rates of complications.3,4

Māori and Pacific Island populations are disproportionately impacted by Meningococcal B disease in NZ

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<1 1-4 5-9 10-14 15-19 20-29 30-39 40-49 50-59 60-69 70+

Average Meningococcal B notification rate 2007-2016

Maori

Pacific Island population

Non-Maori/Non-pacific islandpopulation

1. The Institute of Environmental Science and Research, Meningococcal disease epidemiology data request. GSK. 2017.

Not

ifica

tion

rate

per

100

,000

Age group

Māori and Pacific <1 year olds have

approx. 6 times higher Meningococcal B

rates1

Bexsero (4CMenB) – Vaccine Development Multicomponent Meningococcal group B Vaccine (recombinant, adsorbed)

COMMERCIAL-IN-CONFIDENCE

A capsular vaccine for Meningococcal B?Vaccines with a single subcapsular antigen component do not offer broad protection against Meningococcal B disease

Capsular vaccines

Poorly immunogenic1,2

• Structural homology between the B polysaccharide of the capsule and human tissue1,2

N meningitidis bacterial capsuleImage from Nassif et al. 20023

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

Outer membrane “blebs” of N meningitidisImage from Devoe et al. 19737

1. Finne J, et al. J Immunol 1987;138:4402–44072. Wyle FA, et al. J Infect Dis 1972;126:514–5223. Nassif X et al. Trends Microbiol 2002;10:227–2324. Sadarangani M, et al. Lancet Infect Dis 2010;10:112–124

5. Tan LK, et al. N Engl J Med 2010;362:1511–1520 6. Girard MP, et al. Vaccine 2006;24:4692–47007. Devoe IW, et al. Journal Exp Med 1973;138:1156–1167

Bexsero contains 4 antigenic componentsIdentified using a “reverse vaccinology” approach

18

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 colonisation4

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;177:501-5102. Schneider MC, et al. Nature. 2009;458:890-8933. Comanducci M, et al. J Exp Med. 2002;195:1445-14544. Capecchi B, et al. Mol Microbiol. 2005;55:687-6985. Mazzon C, et al. J Immunol. 2007;179:3904-3916

6. Serruto D, et al. Proc Natl Acad Sci U S A. 2010;107:3770-37757. Bambini S, et al. Vaccine. 2009;27:2794-28038. Martin DR, et al. Clin Vaccine Immunol. 2006;13:486-4919. Vesikari T, et al. Lancet. 2013;381:825-83510.Vogel U, et al. Lancet Infect Dis. 2013;13:416-425

Multiple antigens may provide synergistic killing, improve strain coverage, and insure against mutations9,10

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 studiesincluding 9 randomised controlled clinical trials

250 children 2 to 10 years of age

8776 subjects received at least 1 dose of the vaccine.

Studies included subjects from 2 months of ageClinical trial experience with Bexsero

1. GSK New Zealand. Bexsero Data Sheet, July 2018. Available at http://www.medsafe.govt.nz/profs/Datasheet/datasheet.htm

Bexsero Indication1

Bexsero is indicated for active immunisation against invasive disease caused by N. meningitidis group B strains.

Bexsero is indicated for vaccination of individuals from 2 months of age and older. The use of Bexsero should be in accordance with official recommendations.

1. GSK New Zealand. Bexsero Data Sheet, July 2018. Available at http://www.medsafe.govt.nz/profs/Datasheet/datasheet.htm

Dosing schedules for Bexsero in New Zealand

Dosage: Primary immunisation

Minimum interval between primary

doses Booster

Infants2-5 months* 3 doses ≥ 1 month Second year of life**

Infants6-11 months 2 doses ≥ 2 months Second year of life#

Toddlers and children12 months-10 years 2 doses ≥ 2 months Need not

establishedAdolescents & Adults11-50 years^ 2 doses ≥ 1 month

*The safety and efficacy of the vaccine in infants <8 weeks has not yet been established. No data available# ≥2 months post primary series**≥6 months post primary series

^No data available in individuals above 50 years of age

Administer by deep intramuscular injection, preferably in the anterolateralaspect of the thigh in infants or in the deltoid muscle region of the upper arm in older subjects

1. GSK New Zealand. Bexsero Data Sheet, July 2018. Available at http://www.medsafe.govt.nz/profs/Datasheet/datasheet.htm

Bexsero real world effectiveness data

Bexsero approvals and recommendationsSummary (as of April 2018)

NIPs, National Immunisation Programmes*BEXSERO approved across EU and EEA countries under a centralised procedure (Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, UK; Andorra is not listed in EU SmPC, but follows the same approvals as Spain)†Clinical recommendation in countries where BEXSERO has been approved

19 CLINICAL RECOMMENDATIONS†

NIPs6

39 APPROVALS• EU/EEA: 31 countries (plus Andorra)1*• Other: Argentina2, Australia3, Brazil4,

Canada5, Chile6, Uruguay7, USA8

• Andorra23, Ireland24, Italy25, Lithuania, UK26: NIPs implemented

• USA: Category B national recommendation27

• Australia9, Austria10, Belgium11, Brazil12, Canada13, Cyprus14, Czech Republic15, France16, Germany17, Greece18, Hungary19, Poland20, Portugal21, Spain22

• Andorra23, Ireland24, Italy25, UK26, USA27 (see below)

Please refer to slide notes for references 23

UK: National MenB vaccination programme6,7

Canada: Regional vaccination campaign in Quebec and University outbreak in Nova Scotia

*Under IND protocol prior to US approval (January 2015)IND, investigational new drug

Real world experience with Bexsero

USA: University outbreaks

Princeton University and University of California at Santa Barbara1,2

In 2013, the FDA authorised vaccination campaigns in response to two university outbreaks; surveillance data for 15,236 individuals vaccinated with Bexsero have been reported

Santa Clara3

In 2016, a two-dose vaccination campaign was introduced – 4921 individuals received the first dose in February 2016

Regional campaign in Saguenay–Lac-Saint-Jean, Quebec4

In 2014, 57,038 residents or those in education aged ≥2 months to ≤20 years were targeted for Meningococcal B vaccination to help protect against the high incidence of disease in the region. Between 5 May and 17 June 2014, 43,740 individuals received the first dose of vaccine

Outbreak at Acadia University, Nova Scotia5

In 2015, a two-dose Meningococcal B vaccination campaign was introduced at Acadia University, Nova Scotia – 2967individuals received the first dose in February to March 2015 and 987 participants were assessed in an online safety survey following the first dose

In 2015, universal Meningococcal B infant vaccination was introduced to help protect against Meningococcal B disease in the UK – ~700,000 infants per year were targeted for vaccination

1. Watson P and Turner D. Vaccine 2016;34: 875–80; 2. McNamara et al. Pediatrics 2015; 135:798–804; 3. Biswas et al. Morb Mortal Wkly Rep 2016;65: 520–1; 4. De Serres et al. INSPQ 2014. https://www.inspq.qc.ca/es/node/4122 [Accessed January 2017]; 5. Langley et al. Vaccine 2016;34: 4046–9; 6. Ladhani et al. Arch Dis Child 2016;101:91–5; 7. Parikh et al. Lancet 2016; 388: 2775- 2872

Bexsero use in infants less than 6 months of ageImmunogenicity and co-administration

Dosage and Administration1

Dosage: Primary immunisation

Minimum interval between primary

doses Booster

Infants2-5 months* 3 doses ≥ 1 month Second year of life

*The safety and efficacy of the vaccine in infants <8 weeks has not yet been established. No data available

Administer by deep intramuscular injection, preferably in the anterolateralaspect of the thigh in infants

1. GSK New Zealand. Bexsero Data Sheet, July 2018. Available at http://www.medsafe.govt.nz/profs/Datasheet/datasheet.htm

Bexsero can be co-administered with routine childhood vaccinations1

Bexsero can be given concomitantly with any of the following vaccine antigens, either as monovalent or as combination vaccines1

DiphtheriaTetanus

Acellular pertussisInactivated poliomyelitis

Hepatitis BHaemophilus influenzae type b

Pneumococcal conjugate (7-valent)

MeaslesMumpsRubella

Varicella

• No clinically significant interference in immune response for either Bexsero or the concomitantly administered vaccines

• There is a more frequent occurrence of fever, tenderness at the injection site, change in eating habits and irritability when Bexsero is co-administered with other vaccines

• When given at the same time as other vaccines, Bexsero should be given at separate injection sites

1. GSK New Zealand. Bexsero Data Sheet, July 2018. Available at http://www.medsafe.govt.nz/profs/Datasheet/datasheet.htm

Bexsero use in infants less than 6 months of ageSafety and use of paracetamol

Bexsero was well tolerated in infantsBexsero tolerability compared to routine vaccines (PCV7 and DTPa-IPV-HBV/Hib)Results post dose 1: Local reactions (reported in the 7 days post vaccination)

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% o

f inf

ants

Pain† Erythema Induration Swelling

Legend

Bexsero§

Routine ^(results for DTPa-IPV-

HBV/Hib injection site)

Severe*

1. Gossger N, et al. JAMA 2012;307:573-82 [including supplementary online content]

*Adapted from Gossger et al, 20121

#Bexsero alone, N=626: infants vaccinated with BEXSERO at 2, 4 and 6 months separately from routine vaccines which were administered at 3, 5, and 7 months. Data shown are from the Bexsero time point only;

^Routine alone: N=310. Routine vaccines: PCV7 and DTaP-HBV-IPV/Hib. Infants vaccinated at 2, 3 and 4 months†Pain was categorised as severe if subject cried when injected limb was moved or did not move injected limb. Erythema, induration and swelling were categorized as severe if local reaction was >100 mm.1

• There was no increase in the incidence or severity of the adverse reactions with subsequent doses of the vaccination series1

Bexsero was well tolerated in infantsFor Bexsero when given alone or concomitantly with routine vaccinations, compared to routine vaccinations alone: Post dose 1

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% o

f inf

ants

Changed eating habits

Sleepiness Vomiting Diarrhea Irritability Unusual crying

Rash Fever ≥38°C

Legend

Bexsero + routine*^(2,4,6 months)

Bexsero#

(2,4,6 months)

Routine*§

(2,3,4 months)

Severe†

Fever ≥39°C

1. Gossger N, et al. JAMA 2012;307:573-82 [including supplementary online content]

Adapted from Gossger et al, 20121

*Routine vaccines: PCV7 and DTaP-HBV-IPV/Hib. ^Bexsero+Routine, N=624; #Bexsero alone, N=626: infants vaccinated with BEXSERO at 2, 4 and 6 months separately from routine vaccines which were administered at 3, 5, and 7 months. Data shown are from the Bexsero time point only; §Routine alone: N=310.

†Adverse events for systemic reactions defined as severe if: change in eating habits (child missed more than 2 feedings), sleepiness (child sleeps most of the time and is hard to arouse), vomiting (child has several vomiting episodes and cannot keep food down for prolonged time), diarrhea (child has more than 6 liquid stools, with no solid consistency), irritability (child is unable to be consoled), and unusual crying (unusual, high-pitched screaming, unlike the child’s normal crying, that persists for ≥3 hours). Rash was categorized as any (shown) or urticarial; fever was categorized as axillary temperatures ≥38°C and ≥39°C.1

• There was no increase in the incidence or severity of the adverse reactions with subsequent doses of the vaccination series1

Impact of prophylactic paracetamol on feverWhen Bexsero was given concomitantly with routine infant vaccines at 2, 3 and 4 months of age (after any dose)

1. Prymula et al. Hum Vaccin Immunother 2014; 10:1993-2004

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NPP PP* NPP PP* NPP PP*

% S

ubje

cts

Legend

≥40°C

39°C to <40°C

38.5°C to <39°C

6 hours Day 2 Day 3

Adapted from Prymula et al, 20141

*Subjects received 1 dose of 10–15 mg/kg oral paracetamol before vaccination, followed by 2 additional doses of paracetamol at 4–6 hour intervals after vaccination.

Routine vaccines: PCV7 and DTaP-HBV-IPV/Hib.

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

• Use of paracetamol resulted in a significant reduction in the incidence and severity of fever following administration of Bexsero without compromising vaccine immunogenicity1

*Routine: PCV7 and DTaP-HBV-IPV/Hib.†N=119–140, except HBV: N=65–66.‡For initially seropositive subjects (baseline ≥lower limit of quantification [LLQ]), maintenance of pre-vaccination levels; if baseline <LLQ (initially seronegative subjects), post-third dose ≥LLQ.This study was not powered for a noninferiority analysis. Each vaccine group followed a 2-3-4 month accelerated schedule.Blood draw at 5 months.

Antigens

BEXSERO®+Routine*,† BEXSERO®+Routine+Paracetamol*,†

100 100 98 97 97 99 96 100 97 98100 100 97 97 91 97 96 100 97 990

20

40

60

80

100

Diphtheria Tetanus PT FHA PRN Polio 1 Polio 2 Polio 3 HBV PRP-Hib% ≥0.1 IU/mL

% ≥0.1 IU/mL

–3%(–8, 1)

0%(–6, 6)

0%(–3, 3)

–2%(–7, 3)

1%(–4, 6)

–6%(–13, 0)

0%(–3, 3)

0%(–3, 3)

0%(–8, 8)

1%(–2, 5)

% ≥0.15 mcg/mL

% ≥10 mIU/mL% ≥1:8% serocoversion‡

% S

eror

esp

onse

or

% se

roco

nver

sion

Prymula R, et al. Hum Vaccin Immunother. 2014;10:1993-2004.

Prophylactic paracetamol had no clinically relevant impact on immunogenicity of routine vaccinesBexsero given concomitantly with routine infant vaccines (2-3-4 month schedule)

Bexsero safety, presentation and storage

Important safety considerations1

• Bexsero is not expected to provide protection against all circulating Meningococcal B strains

• No data in:

• subjects above 50 years of age or in patients with chronic medical conditions

– Although no natural rubber latex is detected in the syringe tip cap, the safe use of Bexsero in latex-sensitive individuals has not been established.

• Bexsero may contain Kanamycin (< 0.01 micrograms/dose; used in early manufacturing process but removed at later stages). Safe use of Bexsero in kanamycin-sensitive individuals has not been established

Precautions

1. GSK New Zealand. Bexsero Data Sheet, July 2018. Available at http://www.medsafe.govt.nz/profs/Datasheet/datasheet.htm

– Please review New Zealand Data Sheet for further information

Presentation and storage

Presentation0.5mL suspension in a pre-filled syringe (needles not supplied)Upon storage of the suspension product, a fine off-white deposit may form. Shake the vaccine well before use. Visually inspect for particulate matter or discoloration.

Shelf life 3 years

StorageStore in a refrigerator (2-8°C)Do not FreezeProtect from light

Summary

• Invasive meningococcal disease is a rare, but potentially fatal disease

• Serotypes B and C cause the majority of IMD in New Zealand.

• In 2016, 70% of meningococcal cases that could be typed were group B

• Bexsero is a multicomponent, meningococcal serogroup B, recombinant protein vaccine

• Induces production of bactericidal antibodies

• Vaccine immunogenicity and safety has been evaluated in 13 clinical trials

• Indicated for use in individuals ≥ 2 months of age or according to official recommendations

• Acceptable safety and tolerability profile

• Use of prophylactic paracetamol is recommended when administered to infants and children under 2 years of age

Bexsero Prescribing InformationBexsero® (Multicomponent Meningococcal group B Vaccine) is available as a private-purchase prescription medicinefor active immunisation against invasive disease caused by N. meningitidis group B from 2 months of age. The use ofBexsero should be in accordance with official recommendations- a prescription charge will apply. A trainedpharmacist can also administer Bexsero to a person aged 16 years and older. A single 0.5mL dose contains 50mcg ofNeisseria meningitidis Group B Neisseria Heparin Binding Antigen fusion protein, 50mcg of Neisseria meningitidisGroup B Neisseria Adhesin A protein, 50mcg of Neisseria meningitidis Group B Factor H Binding Protein fusionprotein, 25 mcg of Outer membrane vesicles (OMV) from Neisseria meningitidis group B strain NZ98/254 measuredas amount of total protein containing the PorA P1.4. Dosage and Administration: Administered by deepintramuscular injection. 0.5ml dose in a pre-filled syringe. Infants (2-5 months): 3 doses (≥1 month interval), boosterdose at 12-23 months (≥6 month interval between primary series and booster). Unvaccinated infants (6-11 months):2 doses (≥2 month interval), booster dose at 12-23 months (≥2 month interval between primary series and booster).Unvaccinated toddlers and children (12 months – 10 years): 2 doses (≥2 month interval), need for booster notestablished. 11-50 years: 2 doses (≥1 month interval), need for booster not established. Contraindications:Hypersensitivity to any vaccine component. Precautions: Bexsero should never be administered intravenously,subcutaneously or intradermally. Postpone vaccination during acute severe febrile illness. Anticipate psychogenicresponse (syncope, hyperventilation). Manage fever (prophylactic antipyretics). Individuals with impaired immuneresponsiveness. No data for use in subjects aged ≥50 years or patients with chronic medical conditions. Apnoea invery premature infants. Kanamycin-sensitive individuals. Pregnancy (category B1). Lactation. May contain latex. Aswith any vaccine, vaccination with Bexsero may not protect all vaccine recipients. Bexsero is not expected to provideprotection against all circulating meningococcal group B strains. Bexsero should be administered at separateinjection sites. Adverse reactions: Infants & Toddlers: eating disorders, sleepiness, unusual crying, diarrhoea,vomiting, rash, fever (≥39.5°C), injection site reactions, irritability, arthralgia. Adolescents & Adults: headache,nausea, injection site reactions, malaise, myalagia, arthralgia. This is not a full list. Before prescribing Bexsero,please review the full Data Sheet at www.medsafe.govt.nz. Bexsero is a registered trade mark of theGlaxoSmithKline group of companies. Marketed by GlaxoSmithKline NZ Ltd, Auckland.

Adverse events involving GlaxoSmithKline products should be reported to GSK Medical Information on 0800 808500.