PATH Malaria Vaccine Initiative: Current status, future plans Christian Loucq, MD Director, PATH Malaria Vaccine Initiative 5 June 2008 GAVI Alliance
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PATH Malaria Vaccine Initiative: Current status, future plans
Christian Loucq, MDDirector, PATH Malaria Vaccine Initiative5 June 2008GAVI Alliance
Discussion Points for Today
About the PATH Malaria Vaccine Initiative (MVI)
Current status of malaria vaccine development
The way forward: critical ingredients for success
To accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world
A world free from malaria
Founded in 1999Donors: Bill & Melinda Gates Foundation, USAID,ExxonMobil, private individuals
Availability:– Global access– Regulatory & policy pathways
Accessibility:– Preparing countries for the
vaccine introduction– Decision-making framework
To accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world
A world free from malaria
What is the Goal of the Malaria Vaccine Community?
To develop an 80% efficacious malaria vaccine by 2025 that would provide protection for at least four years.
MVI: A global program of PATH
TechnicalAdvisory Groups
MVI Director
MVILeadership
Team
R&D PortfolioManagementCommittee
TechnicalAdvisory Groups
Vaccine Science Portfolio
Advisory Council
VaccineProject Teams
VaccineProject Teams
VaccineProject Teams
VaccineProject Teams
VaccineProject Teams
VaccineProject Teams
VaccineProject Teams
BusinessDevelopment Teams
BusinessDevelopment Teams
Unit StaffMembers
UnitHeads
Business AdvisoryCouncil
MVI Organizational Structure,May 2008
Discussion Points for Today
About the PATH Malaria Vaccine Initiative (MVI)
Current status of malaria vaccine development
The way forward: critical ingredients for success
First, A Word about Malaria
Parasites
Mosquitoes
Humans
ww
w.fd
a.go
v
Malaria’s Reach and Retreat
Age Distribution of Severe Malaria
0.14
0.12
0.1
0.08
0.06
0.04
0.02
01-2mos
3-4mos
5-6mos
6-12mos
1 2 3 4 5 6 7 8 9
Age group
Pro
porti
on A
ffect
ed
Gupta et al., Nature Medicine 5: 340-342, 1999
SukutaKalifi
NKalifi
SSiaya
Targeting the Parasite Lifecycle
If the vaccine targets….
Its goal is to….
Pre-
erythrocytic Stage
Prevent infection
Blood-stage Reduce clinical disease
Sexual transmission blocking
Prevent the spread of parasites by mosquitoes
*Source: The Malaria Product Pipeline, The George Institute for International Health, September 2007, modified to reflect recent changes in MVI’s portfolio
0
5
10
15
20
25
30
Preclinical Safety trials-non-endemic
Safety trials -endemic
Efficacy trials-endemic
MVI sponsored Others
Num
ber o
f vac
cine
can
dida
tes
State of Malaria Vaccine Development Today
GenVecAd5/CSP-
LSA1-Ag2 +Ad5/MSP1-
AMA1
MonashMSP4 & 5ISA 720
ICGEB/BBIPvRIIAS01
WRAIR/GSKAMA1
AS01/AS02
GSKRTS,S
AS01/AS02
ConstructSelection
ProcessDev
Final FormulationToxicology
Phase 1aPhase 1/2a Phase 1b Phase 2b Phase 3
SanariaPfSPZ
MVDBAMA1-C1ISA 720
LaTrobeMSP2
ISA 720
MVI’s Portfolio (June 2008)
Adjuvanted Recombinant Proteins
Viral Vectored
Live Attenuated
Evaluation Technologies
Vaccine Efficacy after 18 MonthsChildren 1–4 years of age, Mozambique
0
0.1
0.2
0.3
0.4
0.5
0.6
1°
Casedefinition
35.3%95% CI 22-
47 p < 0.0001
0.02
0.04
0.06
0.08
0.1
0.12
Severemalaria
0
48.6%95% CI 12-
71 p = 0.02
ControlRTS,S/AS02
Alonso et al., Lancet 2005;366:2012-18
Rat
e (e
vent
s/P
YA
R)
Efficacy vs. Clinical Malaria over Four Years Children 1–4 years of age, Mozambique
Kaplan Meier curve
Source: Macete, ASTMH, 2007; GSK
*Vaccine Efficacy over 4 years (Clinical Malaria): 30.5 p<0.001 (95% CI 18.8-40.4)
Vaccine Efficacy over 4 years (Severe Malaria, not shown): 38.3 p=0.045 (95% CI 3.4-61.3)
*VE _time to first episode; the presence of P. falciparum asexual parasitemia > 2500 per µL & the presence of fever >37.5 at the time of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility.
IHDRC, Bagamoyo
CISM, Manhiça
RTS,S MVI-GSK Program in Africa
HAS, Lambarene
KHRC, KintampoKCCR, Kumasi
JMP, Korogwe
KEMRI -
Kilifi
KEMRI -
Kisumu
RTS,S Clinical Research Center Network
IRSS -
Centre Muraz
KCH, Lilongwe
Objective of the RTS,S Program
To successfully test the most advanced malaria vaccine that may protect infants and children,living in malaria endemic regions, from Plasmodium falciparum malaria disease
WHO Vaccine Prioritization Vaccines that may be licensed by 2012
(WHO SAGE, November 2007)
15
16
16
17
21
31
43
54
65
66
66
66
68
0 20 40 60 80 100 120 140 160 180
Mumps
Hep E
Hep A
Varicella
Rubella
Meninge B
Dengue
Typhoid
Rotavirus
Yellow fever
JE
Rabies
Cholera
Cervical cancer
Meningecoccal A
Influenza
Pneumococcal
Malaria
Weighted priority score based upon expert opinion
Swiss Tropical Institute modelling:
• Based on a vaccine with 52% efficacy against infection (Tanzania)
• Estimated 942 lives per 100,000 population saved over a 20 year period*
• In Tanzania alone, save 375,000 deaths over 20 years
*Extrapolated from: TEDIOSI, F. G. HUTTON, N. MAIRE, T. SMITH, A. ROSS, AND M. TANNER. PREDICTING THE COST-EFFECTIVENESS OF INTRODUCING A PRE- ERYTHROCYTIC MALARIA VACCINE INTO THE EXPANDED PROGRAM ON IMMUNIZATION IN TANZANIA. Am. J. Trop. Med. Hyg., 75(Suppl 2), 2006, pp. 131–143
Estimates of Impact, Cost, and Cost-effectiveness
Estimates of Impact, Cost, and Cost-effectiveness
Swiss Tropical Institute modelling:
• Cost per fully-immunized child ranges from $4.73 to $34.43*, for vaccine price ranges of $1 to $10 per dose– For Tanzania, could be $6.3 million up to $45.5
million per year• Cost-effectiveness for vaccine priced at $1-$10/dose**
– $450–$3,500 per death averted – $12–$96/DALY averted
*Extrapolated from -
HUTTON, G. AND F. TEDIOSI. THE COSTS OF INTRODUCING A MALARIA VACCINE THROUGH THE EXPANDED PROGRAM ON IMMUNIZATION IN TANZANIA. Am. J. Trop. Med. Hyg., 75(Suppl 2), 2006, pp. 119–130
**TEDIOSI, F. G. HUTTON, N. MAIRE, T. SMITH, A. ROSS, AND M. TANNER. PREDICTING THE COST- EFFECTIVENESS OF INTRODUCING A PRE-ERYTHROCYTIC MALARIA VACCINE INTO THE EXPANDED PROGRAM ON IMMUNIZATION IN TANZANIA. Am. J. Trop. Med. Hyg., 75(Suppl 2), 2006, pp. 131–143
Task Name Start Finish
Global Policy pathway on use of RTS, S 10/2/2006 12/5/2012
Annual TAG reviews status of pathway 12/4/2007 12/5/2012
Annual TAG reviews status of pathway 1/25/2007 1/26/2007
WHO Immunization, Vaccines and Biologicals (IVB)decision on use of RTS,S
10/2/2006 11/24/2011
Strategic Advisory Group of Experts (SAGE) 10/2/2006 11/24/2011
Preparations for SAGE 1 meeting - Horizon scanning 10/2/2006 11/21/2006
SAGE 1 - Horizon scanning 11/22/2006 11/22/2006
Preparations for SAGE 2 briefing 1/1/2008 3/31/2008
SAGE defines Immunization Policy Questions 12/3/2007 2/22/2008
SAGE 2 Briefing 4/1/2008 4/2/2008
Preparations for SAGE 3 briefing 12/31/2008 3/31/2009
SAGE 3 Briefing 4/1/2009 4/2/2009
Preparations for SAGE 4 meeting 12/31/2009 3/31/2010
SAGE 4 reviews phase 3 trial data 4/1/2010 4/2/2010
Preparations for SAGE 5 meeting 6/22/2011 11/22/2011
Position paper: draft, review and edit 6/22/2011 11/22/2011
SAGE 5 recommends use of malaria vaccine 11/23/2011 11/24/2011
ECBS issues standards on malaria vaccineproduction
12/4/2007 6/2/2008
Prepare info for ECBS 12/4/2007 2/4/2008
WHO ECBS meeting 6/2/2008 6/2/2008
GACVS advice on safety of RTS,S 1/1/2008 4/1/2010
Prepare info for GACVS I 1/1/2008 2/28/2008
GACVS I - Initial review of safety data 3/31/2008 3/31/2008
GACVS II - Full review of safety data after Phase 3(before SAGE)
4/1/2010 4/1/2010
WHO Global Malaria Programme decision on use ofRTS,S (Scientific and Technical Advisory Group,STAG)
12/3/2007 6/24/2010
TRAC working group defines Malaria Policy Questions 12/3/2007 2/22/2008
Joint Working Group STAG/SAGE 4/1/2010 6/23/2010
STAG decision on RTS,S 6/24/2010 6/24/2010
Roll Back Malaria Partnership review of RTS,S 10/2/2006 2/28/2011
GAVI-GFATM agree roles on malaria vaccine 3/2/2007 11/29/2011
GAVI Alliance Board decision on support for RTS,S 1/1/2009 11/28/2011
GFATM decision on support for RTS,S 1/1/2008 11/28/2011
UNICEF supports use of malaria vaccine 4/5/2010 6/6/2011
Regulatory pathway 1/1/2007 1/2/2012
Financial and procurement pathway 1/1/2010 7/5/2013
GAVI Alliance implements decisions on malariavaccine applications
11/29/2011 11/9/2012
GFATM implements decisions on malaria vaccineapplications
11/25/2011 4/16/2013
UNICEF Supply Division (SD) procures vaccine 1/1/2010 7/5/2013
Manufacturer's pathway 10/2/2006 1/17/2013
African regional pathway 1/24/2006 10/4/2011
National Implementation Pathway 1/1/2008 10/1/2013
National commitment to introduce malaria vaccine 1/1/2008 8/20/2013
National introduction plan implemented 1/31/2012 10/1/2013
Final WHO SAGE Position just after EMEA Opinion
Joint review by SAGE and STAG
Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q42006 2007 2008 2009 2010 2011 2012 2013
Malaria Vaccine Policy Pathway
Strategic Vision for RTS,S Implementation
To ensure that all countries in sub- Saharan Africa have the data and processes they require to make an informed decision on vaccine use, within 1– 3 years of legal and physical availability.
www.malvacdecision.net
Sanaria: A Different Approach
• Targets the whole parasite
• Uses a live, attenuated parasite
Discussion Points for Today
About the PATH Malaria Vaccine Initiative (MVI)
Current status of malaria vaccine development
The way forward: critical ingredients for success
GenVecAd5/CSP-
LSA1-Ag2 +Ad5/MSP1-
AMA1
MonashMSP4
ICGEB/BBILPvRII
WRAIR/GSKAMA1
AS01/AS02
GSKRTS,S
AS01/AS02
ConstructSelection
ProcessDevelopment
Final FormulationToxicology
Phase 1aPhase 1/2a Phase 1b Phase 2b
SanariaPfSPZ
MVDBAMA1-C1ISA720
LaTrobeMSP2
ISA720
Pro
duct
C
andi
date
sR
esea
rch
Pro
gram
s
Research and Development Challenges
• No vaccine has ever been developed for human use against a parasite
• There are no known correlates of immunity for malaria vaccines to establish proof of concept
Antigens
Platforms
Evaluation Technologies
Adjuvants/Formulations
≥80%Efficacious
Vaccine
Pre-erythrocyticBlood-stage
Viral/ BacterialVectors, Virosomes,etc.
TLR agonists, etc.
ELISA, GIAT cell, ADCI
Human Challenge
Research and Development Strategy
Partnerships
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