Transcript The Public Health Impact of Pneumococcal Vaccination

PREVENAR13
Emerging New Data
&
PMS India Report On PCV7
Dr. Gautam Rambhad
Associate Director Medical Services
24st December 2011
1
JOURNEY OF PREVENAR IN INDIA

Prevenar (PCV7) was launched in June 2006

DCGI – Request to conduct PMS study

Prevenar13
India launch - July 2010
Approved in 115 countries*
Launched in 106 countries*
2
* As of Dec 2011
2
Extensive experience with PCV7
IPD
•
•
•
•
•
•
•
•
USA: 76% decrease in overall IPD (<5 years)
USA: 100% decrease in vaccine-type IPD (<5 years)
UK: 98% decrease in vaccine-type IPD (<2 years)
Germany: 90% decrease in vaccine-type IPD (<2 years)
Norway: 95% decrease of vaccine-type IPD (<5 years)
Ireland: 84% decrease in vaccine-type IPD (<2 years)
Belgium: 97% decrease in vaccine-type IPD (<5 years)
Netherlands: 90% decrease in vaccine-type IPD (<2 years)
Pneumonia
•
•
•
•
•
USA: 22% reduction in all-cause CAP hospitalizations (<1 year)
USA: 39% reduction in all-cause CAP hospitalizations (<2 years)
USA: 52% reduction in all-cause CAP hospitalizations (<2 years)
UK: 22% reduction in empyema-related hospitalization (<15 years)
Italy: 15.2% reduction in all-cause CAP hospitalizations (<2 years)
AOM
•
•
•
•
•
Greece: 48% reduction in pneumococcal AOM visits (<14 years)
Greece: 38% reduction in overall AOM episodes (<14 years)
USA: 42.7% reduction in ambulatory visits for AOM (<2 years)
Sweden: 26% reduction in AOM episodes (<2 years)
Italy: 36.4% reduction in vaccine-type AOM hospitalizations (<2These
years)
slides have been
NP carriage
• Netherlands: 92% reduction in vaccine-type carriage (at 24 months) HCPs for the
purposes of medical
• UK: 69% reduction in vaccine-type carriage (<4 years)
education
provided by Pfizer to
3
3
PREVENAR13 – Moving towards the Adult Franchise
November 16, 2011
Prevenar13 : US-FDA considers ‘protection of adults/elderly
from IPD and non-bacteremic pneumococcal pneumonia to
be a meaningful therapeutic benefit’over existing
treatments‘1
22 September 2011
Prevenar13: Active immunization for the prevention of IPD
caused by Streptococcus pneumoniae in adults aged 50
years and older.2
To date, over 50 nations have approved Prevenar 13 adult use - Thailand,
Australia, Bolivia, Philippines and a host of European countries among them3
1. http://www.medscape.com/viewarticle/753734_print accessed on December 20, 2011
2. Summaries of positive opinion 22 September 2011 EMA/CHMP/763049/2011 accessed December 20, 2011
3. http://www.pharmaceutical-int.com/news/fda-panel-approves-prevnar-13-adult-use.html accessed Nov 20, 20114
Prevenar13 - Countries shifting back1
Hong Kong
December 5, 2011
*Notably, the number of childhood IPD caused by serotype 3 has increased from one
case in 2009 to six cases in 2010. Consequently, among children below 5 years of age,
the proportion of IPD caused by serotypes covered by PCV7*, PCV10* and PCV13 were
70%, 70% and 100% in 2009 changed to 47%, 47% and 93% respectively in 2010.1,2
Australia
OCTOBER 1, 2011
The Northern Territory has notified around 2 cases of invasive pneumococcal
disease caused by type 3, 6A and 19A per year in under 2 years old over the last 3
years.3
1. SCVPD. http://www.chp.gov.hk/files/pdf/recommendations_on_the_use_of_13valent_pneumococcal_conjugate_vaccine_in_cip.pdf
2. http://www.chp.gov.hk/en/view_content/24122.html
3.MEMORANDUM, Department of Health, Australia, 30/08/2011, p.1 (Ref no.DF 2011/3616)
5
Prevenar13 - Countries shifting back2
Canada
November 17, 2010
Recently, both Ontario and Quebec announced they would publicly fund Prevenar13 as
part of the childhood immunization program, largely because it protects against additional
serotypes, notably 19A, not contained in either the 7-valent or the 10-valent vaccine.1
6
PREVENAR13
The Real Life Experience
7
IPD
PCV13
USA
ABC surveillance: early trends for
reduction of IPD in children <2 years after
Prevenar13 introduction
3+1
PCV13 in
April 2010
Incidence of IPD in children <2 years between 20062008 and 2010 (n=14,168)
All serotypes
PCV13 serotypes
60
Incidence (cases per 100,00)
60
PCV13
introduced
50
50
*
40
30
20
20
10
10
0
0
Apr-Jun
Jul-Sep
*p<0.0001
40
30
Jan-Mar
PCV13
introduced
*p<0.0001
Oct-Dec
*
Jan-Mar
Apr-Jun
Jul-Sep
2006-2008
Oct-Dec
2010

Among children <2 years old, rates of overall- and PCV13-serotype-related
IPD were lower only in the fourth quarter of 2010

No significant changes were identified in IPD rates among other age
Thesegroups
slides have been
provided by Pfizer to
HCPs for the
IPD cases (isolation of pneumococcus from sterile sites) were identified through 10 Active Bacterial Core surveillance (ABCs) sites. Isolates were serotyped
to identify
those
purposes
of medical
included in PCV13. Quarterly incidence of IPD (cases per 100,000) in 2010 was compared to 20062008 (2009, year of influenza pandemic, was excluded) .
education
Moore M et al. ICAAC Annual Meeting 2011. Presentation #G1-538
8
8
IPD
PCV13
USA
Multi-hospital study: early trends
for reduction of IPD in children (all ages)
after PCV13 introduction
3+1
PCV13 in
April 2010
Serotyped IPD isolates (1 July 2007 to 30 June 2011)
All isolates
Isolates by serotype
No. of isolates
200
36%
150
100
50
No of isolates
(invasive pneumococcal infections)
90
PCV13
introduced
250
0
80
Serotype 19A
45% in 20102011
70
60
2007-2008
2008-2009
2009-2010
2010-2011
50
40
30
20
10
0
2007-8
2008-9
2009-10
2010-11
Total isolates
Early trends indicate 36% reduction in IPD
cases among 8 children's hospitals for the
12 months starting 4 months after the
introduction of PCV13
19A
7F
3
6C
33F
Serotype
19A cases decreased by 45% in the same
period
These slides have been
provided by Pfizer to
Hospital-based observational study. Children (all ages) with IPD prospectively identified from 8 children’s hospitals in the US since 1993. IPD confirmed by
a central
HCPs
for the
laboratory. Serotype and antibiotic resistance were identified.
purposes of medical
education
Kaplan SL et al. IDSA Annual Meeting 2011. Presentation #LB-1.
9
9
IPD
PCV13
USA
Alaska: reduction of IPD cases in
children <5 years after Prevenar13
introduction
3+1
PCV13 in
April 2010
IPD occurrence in children <5 years
Alaskan Native children
Non-Alaskan Native children
Incidence rate per 100,000
160
160
140
April 2006-March 2009 (Pre-PCV13)
April 2010-March 2011 (Post-PCV13)*
120
140
120
100
100
80
80
71%
60
60
40
40
20
20
0
0
All serotypes
P=0.003
PCV13
serotypes
P=0.01
April 2006-March 2009 (Pre-PCV13)
April 2010-March 2011 (Post-PCV13)*
Non-PCV13
serotypes
P=0.5
100%
All serotypes
P=0.02
PCV13
serotypes
P=0.004
Non-PCV13
serotypes
P=0.9 [NS]
A decrease was noted in non-PCV13 disease among Alaska native children
These slides have been
provided by Pfizer to
State-wide birth cohort study involving the population of children <5. Pneumococcal isolates obtained from sterile sites and reported to Alaska-wide laboratory based
HCPs for the
surveillance sites. *April 2009–March 2010 was excluded because PCV13 was introduced pre-licensure in one high-risk region in 2009. Vaccine coverage in April 2011 was
purposes
of medical
90%, including 2,551 children who were vaccinated during the period AprDec 2010.
education
Bruce M et al. IDSA Annual Meeting 2011. Poster #656.
11
11
IPD
PCV13
USA
Ohio: reduction in overall IPD,
all ages
3+1
PCV13 in
April 2010
IPD incidence
(all serotypes, 19A highlighted)
•
Many of the strains between 2003
and 2009 (43.449.1%) have been
from the 6 additional serotypes now
included in PCV13
150
•
Most of these being serotype 19A,
followed by serotypes 3 and 7F
100
•
Although PCV13 was introduced
only very recently, there has been a
dramatic decrease in 2010 in the
number of pneumococci isolated
overall and in the proportion of
serotype19A strains
250
PCV7
200
No. of isolates
PCV13
Other
19A
50
09
08
10
20
20
20
07
20
06
20
04
05
20
20
03
20
02
20
00
01
20
20
19
99
0
These slides have been
provided by Pfizer to
for the
Observational study. Isolates were sequentially collected. S. pneumoniae isolated in the clinical microbiology laboratory, 19992010. Serotyping was performed HCPs
by capsular
swelling using commercial antisera.
purposes of medical
education
Jacobs MR et al. ICAAC Annual Meeting 2011. Presentation #G3-773.
12
12
IPD
PCV13
UK
UK: early trend for reduction of IPD in
children <2 years after Prevenar13
introduction
2+1
PCV13 in
2010
Cumulative weekly number of IPD reports in children <2 Years in England and Wales by
epidemiological year
PCV7 serotypes
Six additional serotypes in Prevenar 13 but not in PCV7
One year after PCV13 introduced in children <2 years:
 Maintained reduction of PCV7 types IPD
 Decreased number of reported cases of IPD related to 6 additional types included in PCV13
(particularly 19A and 7F types)
These slides have been
Note: The above graph is based on week of isolation, therefore numbers for most recent weeks may not be complete. Numbers of reports of serotyped
cases by
shown
in to
the
provided
Pfizer
graph are not adjusted to account for any change that may have occurred over time and between age groups in the proportion of all IPD cases that are serotyped.
The
7-valent
HCPs for the
conjugate vaccine was introduced into the childhood immunization schedule on the 4 September 2006, which corresponds with week 36 above.
purposes of medical
http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/Pneumococcal/EpidemiologicalDataPneumococcal/CurrentEpidemiologyPneumococcal/InPrevenar7/ .education
Accessed 18th November 2011.
13
13
IPD
PCV13
1, 3, 5, 6A,
6C
combined

7F

UK
Significant reduction of IPD caused by
additional Prevenar13 serotypes in
children <2 years
2+1
PCV13 in
2010
Within one year of PCV13
introduction, IPD cases in
children <2 years due to
additional PCV13 serotypes
were halved
Significant reduction of 7F and
19A reported IPD cases
19A
Miller E et al. Vaccine 2011 Oct 5. ePub ahead of print.
14
These slides have been
provided by Pfizer to
Study population: children who were eligible for PCV13 (one or more doses) who
HCPs for the
reported to the Health Protection Agency with IPD (n=235) and had a complete vaccine
purposes
of medical
history taken. IPD defined as isolation of S. pneumoniae from a normally sterile
site.
education
PCV13 was introduced nationally in week 13, 2010.
14
IPD
PCV13
GER
Reduction in IPD caused by additional
serotypes contained in PCV10 and
Prevenar13 in children <2 years
3+1
PCV13 in Dec 2009
PCV10 in Apr 2009
Cumulative number of 6 additional PCV13 serotypes
isolated from children <2 years with IPD
One year after the
introduction of
higher valent PCVs
first effects are
visible, with less
reported cases
among children <2
years due to
serotypes 1, 3, 6A
and 7F
These slides have been
provided by Pfizer to
National observational study. Data taken from the German National Reference Center for Streptococci (GNRCS) from children <16 years of age with confirmed
IPD between
HCPs
for the
1997 and 2011. Surveillance was passive and taken from diagnostic laboratories located nationwide.
purposes
of
medical
PCV10 & PCV 13 are currently available in Germany
Introduction of PCV10 in April 2009 & PCV13 ineducation
Dec 2009.
Van der Linden M et al. ICAAC Annual Meeting 2011. Presentation #G3-775.
15
15
PCV13
Pneumonia
Reduction in Hospitalization Rates for
Pneumonia with Prevenar13 in children < 2
years
Hospitalization Rates for Bacterial Pneumonia
in Children < 2 years of age
Hospitalization Rates for Pneumococcal Empyema
In Children < 2 years of age
60
1600
1400
50
PCV 7
PCV 7
PCV 13
1200
40
1000
PCV 13
30
800
600
20
400
10
200
0
2005
2006
2007
2008
2009
2010
0
2005
2006
2007
2008
2009
2010
2010 vs. 2005-2007
79.0%
47.4%
WHO defined Radiological Pneumonia:
↓ post PCV13 introduction
Pirez MC et al. SLIPE, May 2011, Punta Cana, Dominican Republic
16
NPC
PCV13
USA
Significant reduction of NP carriage of
6 additional Prevenar13 serotypes in
children <1 year
3+1
PCV13 in
April 2010
NPC rates (%); children
p=NS
Age <12 months
25%
2006/2007
2010/2011
20%
15%
p=0.002
10%
5%
0%
S. Pneumoniae carriage
Additional 6 PCV13 serotype
carriage
Decline in vaccine-type
carriage
prevalence
observed
for
the
6
additional
vaccine
serotypes in children <12
months, but not in children
1259 months
Age 1259 months
40%
p=0.01
2006/2007
30%
2010/2011
20%
Observational study. Nasopharyngeal surveillance was
performed in children <60 months of age attending the
primary care center (PCC) at Boston Medical Center. NP
cultures were collected after obtaining informed consent and
processed by routine microbiologic methods.
p=NS
10%
0%
S. Pneumoniae carriage
Hsu K et al. IDSA Annual Meeting 2011. Abstract. #666
17
These slides have been
provided by Pfizer to
HCPs for the
purposes
of medical
PCV13 serotype
education
Additional 6
carriage
17
PCV13
Early, widespread evidence of a positive
PCV13 impact at a global level
IPD: Alaska, USA
IPD: ABC, USA
Pneumonia:
Uruguay
IPD: HPA, UK
1600
140
Incidence (cases per 100,00)
Incidence rate per 100,000
160
April 2006-March 2009 (Pre-PCV13)
April 2010-March2011 (Post-PCV13)*
120
100
80
60
60
*p<0.0001
1400
50
1200
*
40
1000
30
800
20
600
10
400
200
0
40
Jan-Mar
Apr-Jun
Jul-Sep
Oct-Dec
0
2005
20
2006
2007
2008
2009
2010
0
All serotypes
PCV13
serotypes
P=0.003
Non-PCV13
serotypes
P=0.01
IPD: Germany
P=0.5
IPD: USA
250
No. of isolates
200
150
100
50
0
2007-8
2008-9
2009-10
2010-11
Total isolates
IPD: Ohio, USA
Carriage: France
250
Age <12 months
25%
150
2006/2007
2010/2011
20%
100
15%
p=0.002
10%
50
5%
0%
09
08
07
06
05
04
03
02
10
20
20
20
20
20
20
20
20
20
00
01
20
20
99
0
S. Pneumoniae carriage
Additional 6 PCV13 serotype
carriage
18
P<0.001
Percentage of isolates (%)
p=NS
19
No. of isolates
200
25
Carriage: Boston, USA
Other
19A
19.4
20
PCV13 vaccinated (N=652)
P<0.001
non PCV13 vaccinated (N=290)
14.4
15
10
9
6.8
P=0.01
5
2.5
0.5
0
6 add
PCV13 STs
19A
7F
2.5
1.2
0.5 0
0 0
6A
5
0 0
3
1
Early evidence
needs to be
These slides have been
provided
by Pfizer by
to
confirmed
HCPs for the
continuous
purposes of medical
education
surveillance
18
PREVENAR
The India PMS Study
19
PREVENAR PMS INDIA
Study Objective

To collect safety and tolerance data on PREVENAR for
primary immunization and catch-up population
Study Design

Open-label, multi-center, non-comparative, prospective
phase IV post-marketing observational study

A total of 161 investigators recruited 1094 children into the
study
20
20
PREVENAR PMS INDIA
Inclusion
Criteria
Inclusion
Criteria

For Primary Immunization Schedule:
Healthy male or female subjects 6 weeks + 5 days of
age with no previous PREVENAR vaccination

For Catch-up Immunization Schedule:
Healthy male or female subjects 12-23 months of age
21
21
PREVENAR PMS INDIA
Exclusion Criteria

Known or suspected history of Streptococcus pneumoniae disease

Previous anaphylactic or other severe vaccine-associated adverse
event

Known or suspected impairment of immune system (including HIV
infection)

Recipient of immunosuppressive agents or those with a major
congenital, developmental or serious chronic disorder

Confirmed or suspected underlying evolving neurological disorder
or history of seizures

History of thrombocytopenia or any coagulation disorder

Acute illness at the time of vaccine administration
22
22
PREVENAR PMS INDIA
Study Procedure
Primary Immunization Schedule:
6 weeks onwards
Dose 1
(6 weeks
+5 days)
X
Dose 2*
Dose 3*
(10 weeks (14 weeks
+ 5 days) + 5 days)
X
X
* Minimum 4 week separation between vaccine administrations
Catch-up Immunization Schedule:
From 12 – 23 months of age
23
Dose 1
Dose 2
Dose 3
X
Concomitant vaccine administration allowed in other extremity
23
PREVENAR PMS INDIA
Safety Evaluation

Subject observed for 30 minutes post vaccination

AE was documented in CRF and the subject followed
until all untoward reactions resolved

Parents or guardians were advised to report local
and/or systemic events post-vaccination and report

Serious AE reported within 24 hours to Medical
Department, Wyeth Limited
24
24
PREVENAR PMS INDIA
Demographics
1094 Children
Boys (n=602; 55%)
Girls (n=492;45%)
Primary
(n=810)
Boys
(n=437)
54%
25
Catch Up
(n=284)
Girls
(n=373)
46%
Boys
(n=165)
58.1%
Girls
(n=119)
41.9%
25
PREVENAR PMS INDIA
Distribution of cases
West, n=214
North, n=451
South, n=383
East, n=46
26
26
PREVENAR PMS INDIA
Total Incidences of Adverse Events
18.5
20
17.9
18.4
Percentage of subjects with AE(%)
18
16
14
12
10.2
10.5
9.5
10
8
Primary
Catch Up
Total
6
4
2
0
27
Children with AE
Children with >1 AE
27
PREVENAR PMS INDIA
Adverse Events: Primary Series & Catch up
80
73
70
66
60
Number of Children
60
56
51
47
50
40
30
Dose 1
Dose 2
Dose 3
25
22
Catch Up
20
10
0
28
Lot Fussier than Usual
Lot Sleepier than Usual
Eating Poorly
Warm to touch
Vomiting
Hardness
Diarrhoea
Swelling
Rash
Pain
Redness
28
PREVENAR PMS INDIA
Injection Site Adverse Events
14
Percentage of subjects (%)
12
10
9
8.2
8
7.7
7
6
3
4
2
2.1
2
0.9
0.5
1.1
0.5
0.7
0
0
0.2
0.1
0
29
Redness
Hardness
Primary - 1
Primary - 2
Swelling
Primary - 3
Catch up
Pain
29
PREVENAR PMS INDIA
Completion Status
Catch-up
(n=284)
Primary
(n=810)
Children administered PREVENAR
Dose 1
Dose 2
Dose 3
810
804
803
284
No. of children who completed the study (N, %)
803 (99.13)
284 (100)
No. of early terminations from the study (N, %)
7 (0.86)
0 (0)
6 (87.5)
0 (0)
1 (12.5)
1 (12.5)
Reasons for Early Discontinuation
Lost to follow up (N, %)
Others (N, %)
30
Data represented as [N, (%)]
30
PREVENAR PMS INDIA
Summary

Most frequently reported AEs were pain/tenderness at injection site (9%)
and fever (6.7%)

AEs were not clinically significant and are in line with previous data1

Lesser in incidence compared with AEs reported in Prevenar PI



Other AEs noted (child lot fussier than usual, child lot sleepier than usual,
child eating much more poorly than usual and injection site reactions)
were transient, had < 2% incidence
Incidence of redness, swelling and a lump or hardness was much higher
with concomitant vaccines compared to PREVENAR
The incidence of pain and tenderness at the injection site was higher in
the PREVENAR group
31
Black S, et al Pediatr Infect Dis J 2000; 19(3): 187-195.
31
PREVENAR PMS INDIA
Prevenar:
Taking Pride in Healthy
Babies
32
MERRY XMAS & A HAPPY NEW
YEAR 2012
33