4/3/2017

RTS,S/AS01 Mosquirix
The journey towards a
malaria vaccine
Lode Schuerman
Global Medical Affairs
GSK Vaccines
Belgium

FR/VAC/0020/17 Mosquirix is a trademark of the GSK group of companies

WHO Malaria Vaccine Technology Roadmap

Landmark: By 2015, develop and license a first-

generation P. falciparum malaria vaccine that has a
protective efficacy of more than 50% against
severe disease and death and lasts longer than
one year.

By 2030, license vaccines targeting

P. falciparum and P. vivax
Development of malaria vaccines with a
protective efficacy of at least 75% against
clinical malaria for at-risk groups in endemic
areas
Development of malaria vaccines that reduce
transmission of the parasite. This will enable
elimination in multiple settings through
administration in mass campaigns
WHO Malaria Vaccine Tech. Roadmap, August 2006 updated in November 2013
*http://www.who.int/immunization/topics/malaria/vaccine_roadmap/en/ 2

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 4/3/2017

The 60+ years global quest for a malaria vaccine

The challenge: Pre-erythrocytic vaccine

Protozoan with a large genome
14 chromosomes, 5-6000 genes Antibodies and cellular immune
response to:
Multistage life cycle with stage
Prevent infection of liver cells
specific expression of proteins
Protect against blood-stage
Allelic and antigenic variation/ infection with impact on
polymorphism clinical disease
Human immune response is
complex and genetically variable

Blood-stage vaccine
Transmission-blocking IN MOSQUITO GUT:

vaccine Antibodies to interfere with

merozoites and infected
Antibodies to interfere with
erythrocytes:
parasite development in the
mosquitoes: Impact on clinical disease
No impact on clinical disease
Elimination strategy

Nussenzweig et al, Nature 1967; 5111:160 162 Carneiro et al , 2010 3

Making the circumsporozoite protein immunogenic: RTS,S

The circumsporozoite protein:

is the major surface protein of the sporozoite
helps the parasite bind to liver cells

More than a dozen CS-based antigens were

tested in humans between 1988 and 1995.
All strategies to modify CS to promote
better immune responses, including the
use of adjuvant systems, either failed or did
not increase efficacy against challenge

Gordon DM et al. J Infect Dis 1995;171:157685

4

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 4/3/2017

Making the circumsporozoite protein immunogenic: RTS,S

The circumsporozoite protein:

is the major surface protein of the sporozoite
helps the parasite bind to liver cells

Repeat

Target of T cell
neutralizing epitopes
antibodies

The RTS,S candidate vaccine particles: R T S

HBsAg
The R and T regions from CSP are fused + S
to the hepatitis B surface antigen (HBsAg). HBsAg
The fusion protein is co-expressed with HBsAg in yeast
(Saccharomyces cerevisiae) where they spontaneously
assemble into mixed non-infectious virus-like particles.

RTS,S
Gordon DM et al. J Infect Dis 1995;171:157685
5

GSKs adjuvanted vaccine design principle

RTS,S/AS01
malaria vaccine

AS01
RTS,S antigen
adjuvant system
Specificity of the Designed to enhance and modulate
immune response the immune response to the antigen.
Combines the effect of two or more
immune-enhancers.

RTS,S The goal is to select the right antigen - adjuvant system

combination which can guide the immune response,
delivering enhanced and sustained protection

Garon N et al. Expert Rev Vaccines 2007;6:72339; Leroux Roels G. Vaccine 2010;28S:C25 C36.
6

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 4/3/2017

Impact of enhanced antigen purification on vaccine

immunogenicity and tolerability

Empirical approach Pathogen-based

Observation based Replicating
Jenner (live attenuated pathogen)

Non-replicating Subunit Purified antigens

(whole inactivated pathogen) (toxoids, split virus, (various antigens,
fragments of pathogens) recombinant proteins)

Tolerability
Immunogenicity
Garon N, et al. Expert Rev Vaccines 2007; 6:723739; Melnick J. Rev Infect Dis 1984; 6(Suppl 2):S323S327; Dudgeon J. Nature 1969; 223:674676;
Dougan G & Hormaeche C. Vaccine 2006; 24S2:S2/13S2/19; Garon N & Van Mechelen M. Expert Rev Vaccines 2011; 10:471486

Defense triggers required to induce immune response

Microbial structures contain:

Antigens (antigens alone may exhibit insufficient immunogenicity)
Defense Triggers (Danger Signals), e.g. PAMPs (pathogen-associated
molecular patterns), that act as intrinsic immune-triggers

Specificity of the
immune response
Antigens

Alert immune system

Defence
triggers
Pathogen Adjuvants act as Stimulate/direct
Enhanced substitutes for immune response
purification
natural immune-
defence triggers

Dougan G & Hormaeche C. Vaccine 2006; 24S2:S2/13S2/19; OHagan DT & Valiente NM. Nat Rev Drug Discov 2003; 2:727735.

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 4/3/2017

The RTS,S malaria vaccine development programme:

A 30 year effort from GSK and successful partnerships
2015
2013
Final Phase III efficacy
1995 2011 Third Phase III results including
efficacy results over 3 4 years of follow up
1984 First clinical 2004 First Phase III 18 months of follow and effect of 4th dose of
tests begin in efficacy results in up and per study RTS,S(14)
GSK/WRAIR adults in US Key Proof of
initiate 1998 Concept study
2009 5 17 months old site(13)
over 12 months of
collaboration in children in Phase III
First trials in follow up(11)
Africa begin Mozambique(1,8) efficacy
in the Gambia(4) study start

1997 2011 2014 2015

1987 Key proof of 2007 Key Phase II 2012 File submitted EMA Positive
concept study efficacy results in to the European Scientific
RTS,S first
created by
shows 6 out of 7 2001 Phase II results African children Second Phase III Medicines Opinion
volunteers in in African children(5) (6) and infants(7,9) efficacy results Agency (EMA) granted(15)
combining challenge trial are GSK/MVI and infants(2,10) in 6 12 weeks old
the malaria fully protected(3) partnership over 12 months of WHO
CS protein initiated follow up(12) recommends
and hepatitis B pilot
surface antigen introduction(16)

(1) Alonso P et al. Lancet 2004; (2) Aponte J et al. Lancet 2007; (3) Stoute J et al. NEJM 1997; (4) Doherty J et al. AJTMH 1999; (5) Bejon P et al. NEJM 2008; (6) Olotu A et al. Lancet ID 2011;
(7) Asante KP et al. Lancet ID 2011; (8) Sacarlal J et al. JID 2009; (9) Agnandji ST et al. JID 2010; (10) Abdulla S et al. NEJM 2008; (11) RTS,S Clinical Trials Partnership. NEJM 2011; (12)
RTS,S Clinical Trials Partnership. NEJM 2012; (13) RTS,S Clinical Trials Partnership. PLoS Med 2014; (14) RTS,S Clinical Trials Partnership. Lancet 2015; (15) www.ema.europa.eu; (16)
www.who.int/immunization/research/development/malaria_vaccine_qa/en/ 9

First Proof of Concept for efficacy of the RTS,S vaccine candidate

against Plasmodium falciparum infection
Human challenge model at the Walter Read Army Institute of Research

Vaccine IgG CMI Protected

None - - 0/6

RTS,S/AS04 + + 1/8

RTS,S/AS03 +++ + 5/7

RTS,S/AS02 +++ +++ 6/7

The most efficacious formulation is the one that consistently induced the
best humoral and cell-mediated immune responses in preclinical testing.
Unprecedented breakthrough in malaria vaccine development!

Stoute et al. NEJM 1997:336(2);8691

Sun et al. J of Immunology 2003;171(12):6961-7

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RTS,S/AS01 a potentially improved candidate vaccine formulation

In animal models and clinical studies, several antigens appeared more

immunogenic (particularly for cellular immunity) when formulated with AS01,
with little change in reactogenicity
In a phase I/IIa challenge study, RTS,S/AS01 induced higher antibody response
and higher CD4+ cell response than RTS,S/AS02

Formulation Protected Infected VE

RTS,S/AS02 14 30 31.8% (95% CI: 17.6; 47.6)

RTS,S/AS01 18 18 50.5% (95% CI: 32.9; 67.1)
VE AS01 vs VE AS02: p = 0.11

AS01 was introduced into the clinical development plan of RTS,S

with aim to improve vaccine efficacy and duration of protection

Mettens P et al. Vaccine, 2008; 26:1072-82 - Kester KE et al. J Inf. Dis., 2009; 200: 337-46 11

Summary of pediatric Phase II findings

Consistent efficacy (40-50%) in different malaria transmission settings

in Kenya, Mozambique, Tanzania, Gabon & Ghana:
Trend toward higher efficacy in younger children (with less natural immunity)
Evidence for efficacy against severe forms of the disease
Beneficial effect on clinical disease up to 42 months after the last vaccine dose
Acceptable safety profile:
Over 8,000 doses of RTS,S/AS02 or RTS,S/AS01 administered to more than 3,000
children/infants aged between 6 weeks and 6 months
Reactogenicity pattern comparable to control vaccines (including EPI vaccines)
Trend towards clinical benefit on all cause morbidity and mortality
Can be co-administered within routine infant EPI immunizations
(compatible in terms of safety, efficacy & immune responses)

GSK-MVI partnership decision to

initiate phase III with RTS,S/AS01

Alonso P. Lancet 2004;364:1411 20 Alonso P. Lancet 2005,366:2012 18 Sacarlal J. JID 2009;200:329 36 Bejon P. 2008 NEJM 359;24:2521 32
Aponte J. Lancet 2007;370:1543 51 Abdulla S. NEJM 2008;359:2533 44 Agnandji S. J Infect Dis 2010;202:076 87 Kester K. JID 2009;200:337 46
12
Olotu A. Lancet ID 2011;11:102 09 Asante K. Lancet ID 2011;11:741 49 Vekemans J, Human Vaccines 2011;7:1309 16

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Phase III multicentre efficacy trial of RTS,S/AS01

Double-blind, randomized, controlled trial.

11 centres in 7 African countries.
Wide range of malaria transmission
intensities by site: 0.03-4.27 clinical episodes
per infant during first 12 months of follow-up.
15,459 children enrolled in two age categories:
Children aged 517 months (8,922)
Infants aged 612 weeks (6,537)
Infants received the study vaccine co-
administered with routine vaccines (DTPw-
HepB/Hib+OPV).
High access to health care, malaria
diagnostics and treatment (ACT).
High ITN usage throughout the study: close to
80% in children and somewhat higher in infants

Hay SI. PLoS Med 2009;6:e1000048; Leach A. Malaria J 2011;10:224; RTS,S Clinical Trials Partnership. PLoS Med 2014;11:e1001685 13

Phase III efficacy study design

Follow-up to M20 (before 4th dose) All subjects End of long

comparing R3R+R3C vs C3C followed to M32 term follow-up

R3R: RTS,S/AS01 at Month 0,1,2

R R R 4th dose RTS,S/AS01 at Month 20 R

R3C: RTS,S/AS01 at Month 0,1,2

R R R Comparator at Month 20 C
Randomization
1:1:1
C3C: Comparator at Month 0,1,2
Comparator at Month 20

C C C C

M0 M1 M2 M20 Study
Screening M32
End

Comparator vaccines:
Rabies vaccine in children 5-17 months of age at first dose
Men C conjugate vaccine in infants 6-12 weeks of age at first dose and both age categories at Month 20
Median follow-up until study end:
48 months post Dose 1 (range: 41-55) for children 5-17 months of age at first dose
38 months post Dose 1 (range: 32-48) for infants 6-12 weeks of age at first dose

Leach A. Malaria J 2011; RTS,S Clinical Trials Partnership. NEJM 2011; NEJM 2012; PLoS Med 2014; Lancet 2015 14

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 4/3/2017

RTS,S/AS01 vaccine efficacy against clinical malaria

Age at Vaccine Efficacy* against clinical malaria

vaccination over the first over the entire
12 months study period
of follow-up (46 mo of FU**)

RTS,S RTS,S 39% (34;43)

51% (47;55)
5 to 17 26% (21;31)
RTS,S control
months
(children) control control
M0 M1 M2 M20
(36 mo of FU**)

RTS,S RTS,S 27% (21;32)

33% (26;39)
6 to 12 18% (11;25)
RTS,S control
weeks
(infants) control control

* VE % (95% CI) in ATP cohort from 3rd dose; ** median duration of follow-up from dose 3 to study end
RTS,S Clinical Trials Partnership. NEJM 2011; NEJM 2012; Lancet 2015; European SmPC 15

RTS,S/AS01 vaccine efficacy against severe malaria

Age at Vaccine Efficacy* against severe malaria

vaccination over the first over the entire
12 months study period
of follow-up (46 mo of FU**)

RTS,S RTS,S 29% (6;46)

45% (22;60)
5 to 17 -6% (-35;17)
RTS,S control
months
(children) control control
M0 M1 M2 M20
(36 mo of FU**)

RTS,S RTS,S 21% (-7;42)

37% (5;58)
6 to 12 13% (-17;35)
RTS,S control
weeks
(infants) control control

* VE % (95% CI) in ATP cohort from 3rd dose; ** median duration of follow-up from dose 3 to study end
RTS,S Clinical Trials Partnership. NEJM 2011; NEJM 2012; Lancet 2015; European SmPC 16

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 4/3/2017

RTS,S/AS01 vaccine efficacy against malaria hospitalizations

Age at Vaccine Efficacy* against malaria hospitalizations

vaccination over the first over the entire
12 months study period
of follow-up (46 mo of FU**)

RTS,S RTS,S 37% (24;49)

48% (35;59)
5 to 17 12% (-5;26)
RTS,S control
months
(children) control control
M0 M1 M2 M20
(36 mo of FU**)

RTS,S RTS,S 27% (7; 43)

32% (7;50)
6 to 12 13% (-9;31)
RTS,S control
weeks
(infants) control control

* VE % (95% CI) in ATP cohort from 3rd dose; ** median duration of follow-up from dose 3 to study end
RTS,S Clinical Trials Partnership. NEJM 2011; NEJM 2012; Lancet 2015; European SmPC 17

Importance to complement Vaccine Efficacy estimates with

estimates of potential Public Health Impact

Vaccine efficacy needs to be translated into public health impact in order

to understand the true absolute value of vaccination:
Example: The effect of Human Rotavirus Vaccine on severe rotavirus
gastroenteritis in the first year of life in Malawi and South Africa

Malawi South Africa

- Vaccine Efficacy 49 % 77 %
- Baseline incidence 131 54
(episodes/1,000 infants/year)
- Number of severe rotavirus
gastroenteritis cases averted 67 42
(per 1,000 PYAR)

Madhi S. et al. NEJM 2010;362:289-98 18

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 4/3/2017

Phase III results indicate a potential major public health impact of

RTS,S/AS01

The clinical results showed that RTS,S/AS01 has the potential to provide considerable
public health impact when used in combination with other control measures
Although vaccine efficacy was lower in 6-12 week-old infants, meaningful public health
benefits might still be provided in areas with high disease burden

Children aged 5-17 months Infants aged 6-12 weeks

(4 year follow-up) (3 year follow-up)
OVERALL
Kilifi
Korogwe
Manhia
Lambarene R3C
Bagamoyo R3R
Lilongwe
Agogo Hatched areas in case of
Kombewa reduction in the number of
cases averted at SE* vs.
Kintampo Month 32
Nanoro
Siaya *SE: Study End after a
0 1000 2000 3000 4000 5000 6000 7000 median duration of follow-
0 1000 2000 3000 4000 5000 6000 7000
up of 38 months in 6-12-
Number of clinical malaria cases (secondary case definition) week-olds and 48 months
averted per 1000 vaccinees (ITT) in 5-17-month-olds

RTS,S Clinical Trials Partnership. Lancet 2015;386:3145; ITT: Intention-to-treat 19

Tolerability and safety profile of RTS,S/AS01:

>11,000 children evaluated in clinical trials
Adverse events (AEs):
Most common solicited AEs: fever (27%), irritability (14%) and
local injection site reactions such as pain (16%) and swelling (7%)
Most serious AEs: febrile seizures (within 7 days post-vaccination)
Other AEs: decreased appetite, somnolence, diarrhoea, vomiting and
injection site induration
Serious adverse events (SAEs) occurred at similar frequency between
groups in the Phase III clinical study:
5-17 months 6-12 weeks
R3R R3C C3C R3R R3C C3C
Any SAE 24% 25% 28% 27% 28% 28%
Fatal SAEs 2.0% 1.7% 1.5% 2.3% 2.5% 1.9%

Frequency of related SAEs was low: 0.3% for RTS,S, mainly febrile seizures

RMP www.ema.europa.eu; RTS,S Clinical Trials Partnership. Lancet 2015;386:3145 20

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 4/3/2017

Impact of RTS,S/AS01 on mortality

Phase III study was not designed to show impact on mortality:

In clinical trial setting, good and fast access to health care reduces mortality
Children enrolled in the Phase II trial in Siaya (Kenya) experienced a 70%
reduction in all-cause mortality compared to children not in the trial (1)
The low mortality rate hampers interpretation of mortality endpoints,
especially subgroup analysis that further reduce the statistical power
Gender-specific mortality was analysed post-hoc, upon request: (2)
All-cause mortality in girls across both age categories:
2.4% with RTS,S (123 / 5,091) vs 1.3% in control group (33 / 2,603)
Risk Ratio: 1.91 (1.30 2.79)
Such a difference was not observed in boys (1.8% vs. 2.2%)
None of the fatalities were considered as related to vaccination
Causes of death are multiple and not related to one single event
Results could have been affected by several confounders

(1) M. Hamel et al. ASTMH 2014, abstract 631 (2) Klein S. et al. mBio 2016
21

Example: impact of Rotavirus vaccination on mortality

Clinical Trials Post Marketing Surveillance

No increased risk of A study in Mexico showed a small increased risk of
intussusception was observed intussusception, but no increased risk of fatal
No benefit on mortality was pneumonia after rotavirus vaccination (2)
demonstrated in the large A significant decline in diarrhea-related deaths among
phase III trial (1) Mexican children was observed after introduction of
A potential imbalance of deaths rotavirus vaccination (3)
due to pneumonia was observed Infants <12 mo of age: mortality -41%
between rotavirus and control Children 12 to 23 mo (vaccine coverage ~4%):
vaccine recipients mortality -29%

(1) Cheuvart B. et al. PIDJ 2009; (2) Velzquez R. et al. PIDJ 2012; (3) Richardson et al. NEJM 2010 22

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 4/3/2017

Observations during the RTS,S/AS01 Phase III clinical trial that

require further investigation in phase IV studies
Numerical imbalance of meningitis cases in 5-17 month old age category:
21 in 6,000 children vaccinated with RTS,S/AS01 vs.
1 in 3,000 controls over 4 years of follow-up
No similar imbalance in the 6-12 weeks infant age category:
12 in 4,000 infants vaccinated with RTS,S/AS01 vs.
6 in 2,000 controls over 3 years of follow-up
Different etiologies, no clustering in time-to-onset, probably a chance finding
Trend for more severe malaria after 18 months of follow-up in children who did
not receive a 4th dose of RTS,S/AS01, compatible with rebound
Numerical imbalance of hospitalized severe malaria with coma (BCS 2):
Compatible with cerebral malaria, but diagnosis not clinically confirmed
Time-to-onset not suggesting a direct effect of vaccination, nor an indirect
effect related to rebound
Overall impact on severe malaria remained positive in children having
received 4 vaccine doses
To be further evaluated during phase IV studies and pilot implementations

RMP www.ema.europa.eu; RTS,S Clinical Trials Partnership. Lancet 2015;386:3145 23

EMA positive opinion for RTS,S/AS01 (Mosquirix)

(July 2015)

Positive scientific opinion was granted in July 2015 by the European

Medicines Agency (EMA) following the review of the quality, safety and
efficacy of RTS,S/AS01 under Article 58 (candidate manufactured, but
not for use, in European Union) in collaboration with WHO:
Mosquirix is indicated for active immunization of children aged 6 weeks
up to 17 months against malaria caused by Plasmodium falciparum and
against hepatitis B
Mosquirix should not be used for the prevention of hepatitis B in settings where
prevention against malaria caused by P. falciparum is not sought.

The use of Mosquirix should be based on official recommendations

considering P. falciparum malaria epidemiology in different geographical
areas
The use of other malaria control measures recommended locally should not be
interrupted

Positive opinion conditional upon GSKs commitment to deliver Phase IV

study programme specified in the Risk Management Plan (RMP)

Mosquirix is a trademark of the GSK group of companies; EMA: European Medicines Agency
(http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/document_listing/document_listing_000395.jsp&mid=) 24

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 4/3/2017

Summary of safety endpoints addressed in Phase IV

As described in the RMP agreed with (or to be submitted to) EMA *

Data important important potential risks missing information

source identified
risks
EPI-MAL-002 Febrile Meningitis Effectiveness and impact of RTS,S/AS01 on
EPI-MAL-003 convulsion Hypersensitivity (including clinical malaria, severe malaria, cerebral
WHO pilots* anaphylaxis) malaria and mortality
Potential Immune Mediated Fever upon co-administration with other EPI
Diseases (pIMDs) vaccines known to induce fever (DTPw-
based combination vaccines and PCV)
Safety in HIV-infected children
Malaria-076 Rebound effect Long-term efficacy
EPI-MAL-003 Cerebral malaria* Impact on mortality (overall and by gender)*
WHO pilots*
EPI-MAL-005 Behavioural changes on P. falciparum strain replacement
EPI-MAL-010 usage of other malaria Plasmodium species replacement
WHO pilots* preventive measures
Malaria-073 Immunogenicity of RTS,S/AS01 when co-
administered with Measles, Yellow fever
and Rubella vaccines
Cross immunization against human
catalase

EPAR RMP summary: http://www.ema.europa.eu/docs/en_GB/document_library/Other/2015/07/WC500190200.pdf

* Changes to the Risk Management Plan (RMP) to be submitted to EMA 25

Mathematical modelling provides additional insight in the

potential public health impact (PHI) of RTS,S/AS01

Four different modelling groups provided PHI estimates for RTS,S/AS01:

PHI is reasonably predicted by the mean PfPR 2-10 in a country
PHI is projected to be greatest in settings with PfPR 2-10 >10%,
although positive even at PfPR 2-10 of 5-10%

Modelling of 4 doses of RTS,S given to children 6 months or older, living in

region of PfPR2-10 between 10-65%, predicts that over a 15-year period:
1 malaria death can be prevented per approx. 200 vaccinated children
230 clinical malaria cases can be prevented per 200 vaccinated children

Other factors influencing overall PHI and cost-effectiveness are:

Vaccine efficacy profile (including duration of protection)
Vaccine coverage in real-life settings (including drop off between doses)
Changes in insecticide resistance, or anti-malarial resistance
Changes in access to treatment
Vaccine price

PfPR 2 10 : P falciparum parasite prevalence in children aged 2 10 years; Penny et al, Lancet 2015 26

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 4/3/2017

Mosquirix: the start of the next journey

From vaccine to vaccination

WHO policy
EMA Positive recommendation
Scientific Opinion (January 2016)
(July 2015)
IM administration
3 doses at 1-month interval
4th dose 15-18 months later Pre-qualification
procedure

Marketing authorization
applications
Procurement by
NRA licensure UN agencies
in African countries

Start Phase IV studies and pilots:

benefit-risk in real-life settings

http://www.map.ox.ac.uk 27

WHO recommendation for RTS,S/AS01 (January 2016)1

Joint advice from SAGE 2 and MPAC 3 adopted by WHO in Nov 2015

Pilot implementation in 3-5 settings in sub-Saharan Africa

with moderate-to-high transmission of malaria
3 doses of vaccine between ages 5-9 months, fourth dose 15-18 months later

Projects should address:

Risk-benefit in real-life setting
Feasibility of a 4-dose schedule and coverage of current tools for malaria control
Impact of RTS,S/AS01 on mortality

WHO is working with experts, PATH and GSK on:

Design of pilot implementations
Country selection
Resource mobilization

Phase 4 studies and pilot implementations will be complementary

1) WHO WER January 2016 (http://www.who.int/wer/2016/wer9104.pdf?ua=1)

2) Strategic Advisory Group of Experts on Immunization, 3) Malaria Policy Advisory Committee 28

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 4/3/2017

Pilot implementation projects and Phase IV studies

Plan to have pilot implementation projects in 3 countries

Per country:
- Randomization into vaccinated and unvaccinated clusters
- 30 clusters / arm (approximately 120,000 subjects / arm)
- 4 clusters / arm with sentinel hospital (SH) (16,000 subjects / arm)
Phase IV study area Pilot implementation area

SH SH

SH Vaccinated clusters

SH Unvaccinated clusters
SH

SH Sentinel Hospital part of Phase IV

SH SH Sentinel Hospital part of Pilot

Selected country

2 sentinel hospitals / arm will be included in the Phase IV study

29

The journey towards the RTS,S/AS01 malaria vaccine candidate

CONCLUSION (1/2)

Malaria remains a major public health threat, especially in young children living
in sub-Saharan Africa
The addition of a malaria vaccine to existing interventions could help to achieve
improved and sustained malaria control
Results from clinical trials indicate that RTS,S/AS01 has the potential to help
protect young children living in P. falciparum-endemic regions from malaria and
its consequences
Over the first year after vaccination, RTS,S/AS01 reduced the number of
malaria cases by half in children and by one third in infants
Vaccine efficacy was highest shortly after vaccination and waned over time,
but could be enhanced by a fourth dose
Clinical results to date indicate that RTS,S/AS01 has an overall acceptable
tolerability and safety profile

30

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The journey towards the RTS,S/AS01 malaria vaccine candidate

CONCLUSION (2/2)

RTS,S/AS01 has the potential to provide considerable public health impact when
used in combination with other control measures, especially in areas of higher
malaria transmission
It is important that the proposed implementation studies take place, to ensure
continued investment in malaria vaccine development and in other drugs and
vaccines for tropical diseases
This new malaria intervention could have a major role to play in future malaria
control programs, provided the phase IV studies and pilot implementation
projects show that the safety profile of the RTS,S/AS01 vaccine is acceptable,
give reassurance with regard to the meningitis and cerebral malaria safety
signals, and confirm the feasibility of delivering RTS,S/AS01 according to a four-
dose schedule
In addition, experience gained during the development, evaluation and
deployment of RTS,S/AS01 will be important for future new malaria vaccines

31

Acknowledgments

Participants and families Research Centers and Partners

Study staff
PATH Malaria Vaccine Initiative
GlaxoSmithKline
Malaria Clinical Trials Alliance
Albert Schweitzer Hospital, Lambarene, Gabon
Centro de Investigao em Sade de Manhia,
Manhia, Mozambique
Ifakara Health Institute, Bagamoyo, Tanzania
Institut de Recherche en Science de la Sant, Nanoro, Burkina Faso
KEMRI/CDC Research and Public Health Collaboration,
Kisumu, Kenya
KEMRI-Walter Reed Project, Kombewa, Kenya
KEMRI - Wellcome Trust Research Program, Kilifi, Kenya
Kintampo Health Research Center, Kintampo, Ghana
National Institute for Medical Research, Korogwe, Tanzania
School of Medical Sciences, Kumasi, Ghana
University of North Carolina Project, Lilongwe, Malawi

University of Tbingen, Germany

Prince Leopold Institute of Tropical Medicine, Belgium
University of Copenhagen, Denmark
University of Barcelona, Spain
Swiss Tropical Institute, Switzerland
London School of Hygiene and Tropical Medicine, UK
US Centers for Disease Control and Prevention, USA
University of North Carolina at Chapel Hill, USA
Walter Reed Institute of Research, USA

32

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