Prioritizing new malaria vaccine candidates for further development
Prioritizing new malaria vaccine candidates for further development
Prioritizing new malaria vaccine candidates for further development
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
<strong>Prioritizing</strong> New Malaria<br />
Vaccine Candidates <strong>for</strong><br />
Further Development<br />
The current state of affairs in the<br />
field of <strong>malaria</strong> vaccinology:<br />
Thoughts on how <strong>vaccine</strong><br />
<strong>candidates</strong> should be prioritized<br />
<strong>for</strong> <strong>further</strong> <strong>development</strong><br />
David C. Kaslow, MD<br />
Director, PATH Malaria Vaccine Initiative<br />
ASTMH / November 14, 2012
Thoughts on how <strong>vaccine</strong> <strong>candidates</strong> should be<br />
prioritized <strong>for</strong> <strong>further</strong> <strong>development</strong><br />
• Why prioritize<br />
• What to prioritize<br />
• How to approach prioritization<br />
2
Why prioritize<br />
• No need to prioritize if:<br />
• Resources are unlimited<br />
• Only one choice / no trade-offs between or<br />
within goals / projects<br />
• What is the current state of affairs in the global<br />
<strong>malaria</strong> <strong>vaccine</strong> pipeline<br />
3
Tables of <strong>malaria</strong> <strong>vaccine</strong> projects globally:<br />
"The Rainbow Tables"<br />
UPDATED NOVEMBER 2012<br />
Clinical<br />
Trial Registration No<br />
(click to go to link,<br />
hold down to select<br />
cell)<br />
Trial Sponsor<br />
Preclin. 1a 2a 1b 2b Pivotal<br />
Country/start<br />
date<br />
Country/start<br />
date<br />
Country/start<br />
date<br />
Country/start<br />
date<br />
Country/start<br />
date<br />
Pre-erythrocytic Projects<br />
RTS,S/AS01E<br />
Adenovirus (Ad35)<br />
vectored CS and RTS,S-<br />
AS01 in heterologous<br />
prime-boost regimen<br />
ChAd63/MVA ME-TRAP<br />
ChAd63/MVA ME-TRAP<br />
+ Matrix M<br />
Phase III:<br />
NCT00866619<br />
Phase<br />
I/IIa:NCT01366534<br />
Phase I:<br />
NCT00890019<br />
Phase I/IIa: NCT00890760<br />
Phase I/IIa: NCT01142765<br />
PhaseI: NCT01364883 (V043)<br />
Phase Ib: NCT01379430<br />
(VAC040)<br />
Phase Ib: NCT01373879<br />
(VAC041)<br />
Phase Ib: NCT01450293<br />
(VAC042)<br />
Phase IIb: NCT01666925<br />
(VAC043)<br />
Phase IIb: NCT01658696<br />
(VAC047)<br />
Phase I/IIb: NCT01635647<br />
(VAC050)<br />
Phase<br />
I:NCT01669512<br />
(VAC048)<br />
GSK (Belgium) USA USA<br />
GSK (Belgium)<br />
University of Ox<strong>for</strong>d<br />
(UK)<br />
University of Ox<strong>for</strong>d<br />
(UK)<br />
USA<br />
USA<br />
UK<br />
Aug-12<br />
UK<br />
Kenya<br />
adults<br />
Kenya/June<br />
2010<br />
The<br />
Gambia/June<br />
2010<br />
The Gambia/Oct<br />
2011<br />
Kenya and<br />
Tanzania<br />
children<br />
Kenya / March<br />
2012<br />
Senegal/ Jul/Aug<br />
2012<br />
Burkina Faso /<br />
Nov 2012<br />
Country/start<br />
date<br />
Burkina Faso,<br />
Gabon, Ghana,<br />
Kenya, Malawi,<br />
Mozambique,<br />
Tanzania (2009)<br />
Funder<br />
African Malaria Network Trust (AMANET)<br />
The Bill & Melinda Gates Foundation (BMGF)<br />
(direct funding)<br />
European Union (EU) (direct funding)<br />
European Vaccine Initiative (EVI) (<strong>for</strong>merly<br />
European Malaria Vaccine Initiative (EMVI))<br />
European and Developing Countries Clinical<br />
Trials Partnership (EDCTP)<br />
National Institute of Allergy and Infectious<br />
Diseases (NIAID), of US NIH<br />
PATH Malaria Vaccine Initiative (MVI)<br />
color code<br />
Adenovirus (Ad35)<br />
vectored CS<br />
PfSPZ<br />
Phase Ia:<br />
NCT00371189<br />
Phase Ib:<br />
NCT01018459<br />
Phase I/IIa:<br />
NCT01001650<br />
Phase I:<br />
NCT01441167<br />
NIAID (USA)<br />
http://www.who.int/<strong>vaccine</strong>_research/links/Rainbow/en/index.html<br />
USA<br />
USA<br />
Sanaria, Inc. (USA) USA USA<br />
PfSPZ Phase I/IIa Sanaria, Inc. (USA). USA USA<br />
Polyepitope DNA<br />
EP1300<br />
Adenovirus (Ad35) and<br />
adenovirus 26 (Ad26)<br />
vectored CS in<br />
heterologous primeboost<br />
regimen<br />
PfCelTOS FMP012<br />
Pf GAP p52-/p32-<br />
(Genetically Attenuated<br />
Sporozoites)<br />
CSVAC<br />
Efficacy of Plasmodium<br />
falciparum Sporozoite<br />
Chemoprophylaxis<br />
Vaccine (PfSPZ-CVac)<br />
in Tanzania<br />
(SPOROVAC)<br />
ChAd63/MVA (CS; ME-<br />
TRAP)<br />
Phase Ia:<br />
NCT01169077<br />
Phase I/IIa:<br />
NCT01397227<br />
Phase I/IIa:<br />
NCT01024686<br />
Phase I:<br />
NCT01450280<br />
Phase 1/2a<br />
Phase 1/2a:<br />
NCT01623557<br />
NIAID USA USA<br />
Crucell N.V. (The<br />
Netherlands)<br />
Office of the Surgeon<br />
General, Department<br />
of the Army,<br />
USAMRMC<br />
Seattle Biomedical<br />
Research Institute<br />
(Seattle Biomed)<br />
(USA)<br />
USA<br />
USA<br />
USA<br />
USA<br />
USA (Jan<br />
2012)<br />
USA<br />
University of Ox<strong>for</strong>d<br />
(UK) UK Ireland<br />
Sanaria, Inc. (USA)<br />
University of Ox<strong>for</strong>d<br />
(UK)<br />
UK<br />
TANZANIA<br />
Q1 2013<br />
UK<br />
Burkina Faso<br />
Medical Research Council (MRC), UK<br />
United States Agency <strong>for</strong> International<br />
Development (USAID)<br />
United States Department of Defense (US<br />
DoD)<br />
Wellcome Trust, UK<br />
Industry<br />
Institution<br />
National Government<br />
World Health Organization (WHO/IVR/TDR)<br />
4
Global <strong>malaria</strong> <strong>vaccine</strong> pipeline<br />
Phase 1a<br />
TRANSLATIONAL PROJECTS<br />
Phase 2a<br />
Phase 1b<br />
VACCINE CANDIDATES<br />
Phase 2b Phase 3<br />
ChAd63/MVA ME-<br />
TRAP + Matrix M<br />
(Ox<strong>for</strong>d U)<br />
Ad35.CS/RTS,S-AS01<br />
(GSK/Crucell/WRAIR)<br />
PvCSP-AS01<br />
(WRAIR/GSK)<br />
Ad35.CS.01<br />
(NIAID)<br />
ChAd63/MVA<br />
ME-TRAP<br />
(Ox<strong>for</strong>d U)<br />
RTS,S-AS01<br />
(GSK)<br />
PfSPZ<br />
(Sanaria)<br />
Ad35.CS/Ad26.CS<br />
(Crucell/Seattle<br />
BioMed)<br />
ChAd63/MVA<br />
MSP 1<br />
(Ox<strong>for</strong>d U)<br />
AMA1-C1-<br />
Alhydrogel+CPG<br />
7909 (NIAID)<br />
FMP2.1-AS02A<br />
(AMA1 3D7)<br />
(USAMRMC)<br />
Polyepitope DNA<br />
EP 1300<br />
(NIAID)<br />
ChAd63/MVA<br />
(Ox<strong>for</strong>d U)<br />
ChAd63.AMA1/<br />
MVA.AMA1<br />
(Ox<strong>for</strong>d U)<br />
BSAM-2-Alhydrogel<br />
+ CPG 7909<br />
(NIAID)<br />
GMZ2<br />
(EVI)<br />
PfCelTOS FMP012<br />
(USAMRMC)<br />
ChAd63/MVA<br />
(CS; ME-TRAP)<br />
(Ox<strong>for</strong>d U)<br />
FMP2.1-AS01B<br />
(AMA1 3D7<br />
(USAMRMC)<br />
CSP, AMA1<br />
(PEV 301, 302)<br />
(Swiss TPH)<br />
MSP3 [181-276]<br />
(EVI)<br />
CSVAC<br />
(Ox<strong>for</strong>d U)<br />
PfSPZ<br />
(Sanaria)<br />
NMRC.M3V.Ad.PfCA<br />
(USAMRMC)<br />
EBA 175.R2<br />
(NIAID)<br />
ChAd63.AMA/MVA.<br />
AMA1 +Al/CPG7909<br />
(Ox<strong>for</strong>d U)<br />
PfGAP p52- / p32-<br />
(Seattle BioMed)<br />
NMRC.M3V.D/<br />
Ad.PfCA<br />
(USAMRMC)<br />
SE36<br />
(Osaka U)<br />
SR11.1<br />
(Institut Pasteur)<br />
PfSPZ-CVac<br />
(Ox<strong>for</strong>d U)<br />
Pfs25-EPA<br />
(NIAID)<br />
P. falciparum <strong>vaccine</strong>s: Pre-erythrocytic Blood-stage Transmission-blocking<br />
P. vivax <strong>vaccine</strong>s: Pre-erythrocytic Blood-stage Transmission-blocking<br />
Data source: http://www.who.int/<strong>vaccine</strong>_research/links/Rainbow/en/index.html<br />
5
Thoughts on how <strong>vaccine</strong> <strong>candidates</strong> should be<br />
prioritized <strong>for</strong> <strong>further</strong> <strong>development</strong><br />
• Why prioritize<br />
• What to prioritize<br />
• How to approach prioritization<br />
6
What to prioritize<br />
• Strategic goals<br />
• Specific approaches or targets<br />
• Preferred product characteristics<br />
• Which species<br />
• Which age groups<br />
• What geographies<br />
• With what other <strong>malaria</strong> interventions<br />
• Early versus late-stage <strong>development</strong><br />
• Specific projects<br />
7
The Malaria Vaccine Technology Roadmap<br />
http://www.<strong>malaria</strong><strong>vaccine</strong>.org/files/<br />
Malaria_Vaccine_TRM_Final_000.pdf<br />
8
The Malaria Vaccine Technology Roadmap<br />
• The Malaria Vaccine Technology<br />
Roadmap was launched in 2006 at<br />
the WHO Global Vaccine Research<br />
Forum and established a shared<br />
Vision, Strategic Goal (2025), and<br />
Landmark (2015) <strong>for</strong> <strong>development</strong><br />
of <strong>malaria</strong> <strong>vaccine</strong>s. The Roadmap<br />
also identified 11 Priority Areas in<br />
four categories: research, <strong>vaccine</strong><br />
<strong>development</strong>, key capacities,<br />
policy, and commercialization.<br />
http://www.who.int/<strong>vaccine</strong>_research/diseases/<br />
<strong>malaria</strong>/roadmap_update_jul12/en/index.html<br />
http://www.<strong>malaria</strong><strong>vaccine</strong>.org/files/<br />
Malaria_Vaccine_TRM_Final_000.pdf<br />
9
The Malaria Vaccine Technology Roadmap circa 2006<br />
Priorities circa 2006<br />
• Prevent severe disease<br />
and death<br />
• P. falciparum<br />
• Children under five<br />
• Sub-Saharan Africa and<br />
other highly endemic<br />
countries<br />
• In conjunction with other<br />
<strong>malaria</strong> interventions<br />
http://www.<strong>malaria</strong><strong>vaccine</strong>.org/files/Malaria<br />
_Vaccine_TRM_Final_000.pdf<br />
10
1<br />
2<br />
Reasons to update the Roadmap<br />
• “The need to update the Roadmap Vision and 2025 Strategic<br />
Goal in response to a number of changes since 2006, including<br />
changes in the strategic role of <strong>malaria</strong> <strong>vaccine</strong>s and changes<br />
in <strong>malaria</strong> epidemiology and control status.” 1<br />
• “Further reviews of the vision and strategic goals will occur at<br />
least every 5 years in light of the epidemiological and control<br />
situation at that time and progress with other tools and<br />
technologies. Changes will be made only if necessary. Should<br />
projects aimed at either of the 2 strategic <strong>vaccine</strong> goals reach<br />
major milestone per<strong>for</strong>mance indicators, such as proof of<br />
concept of efficacy, this will trigger a WHO-led consultative<br />
process to develop <strong>new</strong> Landmark goals <strong>for</strong> late stage<br />
<strong>development</strong> of these <strong>vaccine</strong>s.” 2<br />
http://www.who.int/<strong>vaccine</strong>_research/diseases/<strong>malaria</strong>/roadmap_update_jul12/en/index.html<br />
http://www.who.int/<strong>vaccine</strong>_research/diseases/<strong>malaria</strong>/Roadmap_update_<strong>for</strong>_second_public_c<br />
onsultation.pdf<br />
11
Updating the Malaria Vaccine Technology Roadmap<br />
Expanded Vision (draft)<br />
Vision after first public<br />
consultation in October 2012<br />
The <strong>malaria</strong> <strong>vaccine</strong> community will<br />
develop safe and effective <strong>vaccine</strong>s<br />
that prevent disease and death caused<br />
by Plasmodium falciparum and<br />
Plasmodium vivax in <strong>malaria</strong>-endemic<br />
regions. Vaccines that interrupt<br />
<strong>malaria</strong> transmission will contribute to<br />
ensuring that <strong>malaria</strong> is no longer a<br />
significant public health problem, and,<br />
in conjunction with other tools, will<br />
enable <strong>malaria</strong> elimination. Efficient<br />
global coordination and collaboration<br />
will stimulate the <strong>malaria</strong> <strong>vaccine</strong><br />
pipeline and accelerate progress<br />
towards these achievements.<br />
Expanded vision<br />
• Includes P. vivax<br />
• Not restricted to children<br />
under five<br />
• Includes all <strong>malaria</strong>endemic<br />
regions<br />
• Includes <strong>vaccine</strong>s that<br />
interrupt transmission<br />
• In conjunction with other<br />
<strong>malaria</strong> interventions,<br />
contemplates elimination<br />
http://www.who.int/<strong>vaccine</strong>_research/diseases/<strong>malaria</strong>/<br />
Roadmap_update_<strong>for</strong>_second_public_consultation.pdf<br />
12
Updating the Malaria Vaccine Technology Roadmap<br />
Expanded Strategic Goals – Part 1 (draft)<br />
Strategic Goals after first<br />
public consultation in Oct 2012<br />
In the 2025 to 2050 timeframe, license<br />
safe <strong>vaccine</strong>s targeting <strong>malaria</strong><br />
species with significant global disease<br />
burden and encompassing the<br />
following two objectives, <strong>for</strong> use by the<br />
international public health community 1 :<br />
1) Malaria <strong>vaccine</strong>s with a protective<br />
efficacy of more than 80% 2 against<br />
clinical <strong>malaria</strong>, suitable <strong>for</strong><br />
administration to both children and<br />
adults in <strong>malaria</strong>-endemic areas. The<br />
efficacy measure will be an 80%<br />
absolute reduction in incidence of all<br />
episodes of clinical <strong>malaria</strong> over at least<br />
2 years. 3<br />
New strategic goal <strong>for</strong><br />
disease prevention<br />
• Protective efficacy of more<br />
than 80%<br />
• Clinical <strong>malaria</strong><br />
• Over at least 2 years<br />
• Children and adults<br />
• Includes all <strong>malaria</strong>endemic<br />
areas<br />
http://www.who.int/<strong>vaccine</strong>_research/diseases/<strong>malaria</strong>/<br />
Roadmap_update_<strong>for</strong>_second_public_consultation.pdf<br />
13
Updating the Malaria Vaccine Technology Roadmap<br />
Expanded Strategic Goals – Part 2 (draft)<br />
Strategic Goals after first<br />
public consultation in Oct 2012<br />
In the 2025 to 2050 timeframe, license<br />
safe <strong>vaccine</strong>s targeting <strong>malaria</strong><br />
species with significant global disease<br />
burden and encompassing the<br />
following two objectives, <strong>for</strong> use by the<br />
international public health community: 1<br />
2) Malaria <strong>vaccine</strong>s that inhibit<br />
transmission 4 of the parasite and<br />
thereby substantially reduce the<br />
incidence of human <strong>malaria</strong> infection to<br />
achieve elimination in multiple settings,<br />
in conjunction with other <strong>malaria</strong> control<br />
tools. The <strong>vaccine</strong>s should be suitable<br />
<strong>for</strong> administration to people of all ages<br />
in mass campaigns. 5<br />
Additional <strong>new</strong> strategic goal<br />
• Inhibit transmission*<br />
• Reduce incidence of<br />
<strong>malaria</strong> infections<br />
• Achieve elimination in<br />
multiple settings<br />
• All ages<br />
• Mass campaigns<br />
*Not restricted to any one life-cycle<br />
stage or <strong>vaccine</strong> approach<br />
http://www.who.int/<strong>vaccine</strong>_research/diseases/<strong>malaria</strong>/<br />
Roadmap_update_<strong>for</strong>_second_public_consultation.pdf<br />
14
Strategic goals, outcomes, and <strong>vaccine</strong> targets<br />
Goal/impact<br />
Control &<br />
elimination<br />
Saving lives<br />
& preventing<br />
disease<br />
15
Strategic goals, outcomes, and <strong>vaccine</strong> targets<br />
Goal/impact<br />
Control &<br />
elimination<br />
Saving lives<br />
& preventing<br />
disease<br />
Outcome<br />
Transmission<br />
interrupted<br />
Infections<br />
prevented<br />
Cases<br />
averted*<br />
*Impact on asymptomatic reservoir<br />
16
Strategic goals, outcomes, and <strong>vaccine</strong> targets<br />
Goal/impact<br />
Control &<br />
elimination<br />
Saving lives<br />
& preventing<br />
disease<br />
Outcome<br />
Transmission<br />
interrupted<br />
Infections<br />
prevented<br />
Cases<br />
averted*<br />
Vaccine target<br />
Sexual/<br />
sporogonic/<br />
mosquito<br />
(SSM)<br />
Preerythrocytic<br />
(PE)<br />
Blood-stage<br />
(BS)<br />
17
Another level of prioritization<br />
ChAd63/MVA ME-<br />
TRAP + Matrix M<br />
(Ox<strong>for</strong>d U)<br />
Ad35.CS/RTS,S-AS01<br />
(GSK/Crucell/WRAIR)<br />
PvCSP-AS01<br />
(WRAIR/GSK)<br />
Ad35.CS.01<br />
(NIAID)<br />
ChAd63/MVA<br />
ME-TRAP<br />
(Ox<strong>for</strong>d U)<br />
RTS,S-AS01<br />
(GSK)<br />
PfSPZ<br />
(Sanaria)<br />
Ad35.CS/Ad26.CS<br />
(Crucell/Seattle<br />
BioMed)<br />
ChAd63/MVA<br />
MSP 1<br />
(Ox<strong>for</strong>d U)<br />
AMA1-C1-<br />
Alhydrogel+CPG<br />
7909 (NIAID)<br />
FMP2.1-AS02A<br />
(AMA1 3D7)<br />
(USAMRMC)<br />
Polyepitope DNA<br />
EP 1300<br />
(NIAID)<br />
ChAd63/MVA<br />
(Ox<strong>for</strong>d U)<br />
ChAd63.AMA1/<br />
MVA.AMA1<br />
(Ox<strong>for</strong>d U)<br />
BSAM-2-Alhydrogel<br />
+ CPG 7909<br />
(NIAID)<br />
GMZ2<br />
(EVI)<br />
Projects<br />
PfCelTOS FMP012<br />
(USAMRMC)<br />
CSVAC<br />
(Ox<strong>for</strong>d U)<br />
ChAd63/MVA<br />
(CS; ME-TRAP)<br />
(Ox<strong>for</strong>d U)<br />
PfSPZ<br />
(Sanaria)<br />
FMP2.1-AS01B<br />
(AMA1 3D7<br />
(USAMRMC)<br />
NMRC.M3V.Ad.PfC<br />
A(USAMRMC)<br />
CSP, AMA1<br />
(PEV 301, 302)<br />
(Swiss TPH)<br />
EBA 175.R2<br />
(NIAID)<br />
MSP3 [181-276]<br />
(EVI)<br />
ChAd63.AMA/MVA.<br />
AMA1 +Al/CPG7909<br />
(Ox<strong>for</strong>d U)<br />
PfGAP p52- / p32-<br />
(Seattle BioMed)<br />
NMRC.M3V.D/<br />
Ad.PfCA<br />
(USAMRMC)<br />
SE36<br />
(Osaka U)<br />
SR11.1<br />
(Institut Pasteur)<br />
PfSPZ-CVac<br />
(Ox<strong>for</strong>d U)<br />
Pfs25-EPA<br />
(NIAID)<br />
P. falciparum <strong>vaccine</strong>s:<br />
P. vivax <strong>vaccine</strong>s:<br />
Stage of <strong>development</strong><br />
Pre-erythrocytic Blood-stage Transmission-blocking<br />
Pre-erythrocytic Blood-stage Transmission-blocking<br />
18
Thoughts on how <strong>vaccine</strong> <strong>candidates</strong> should be<br />
prioritized <strong>for</strong> <strong>further</strong> <strong>development</strong><br />
• Why prioritize<br />
• What to prioritize<br />
• How to approach prioritization<br />
19
Probability of success (%)<br />
How to approach prioritization<br />
• A wide range of tools<br />
• Most efficient and effective, when done as a portfolio<br />
rather than on a project-by-project basis<br />
• Incents better resource stewardship<br />
• Allows richer strategic trade-offs analyses<br />
Probability of Success (%) vs. Cost vs. NPV<br />
Development costs (x$10M)<br />
(Bubble area is proportional to NPV)<br />
20
Cost<br />
Low<br />
High<br />
A commercial-sector model <strong>for</strong> prioritization:<br />
Portfolio management<br />
Inputs<br />
Metrics<br />
Low<br />
High<br />
Probability of success (POS)<br />
(Bubble area is proportional to NPV)<br />
POS<br />
(risk)<br />
Costs<br />
Value<br />
Probability of technical &<br />
regulatory success<br />
(PTRS)<br />
Commercialization risk<br />
Development costs<br />
Commercialization,<br />
including cost of goods<br />
sold (COGs)<br />
Net present value (NPV)<br />
(discounted cash flow)<br />
“Strategic value”<br />
21
Adaptation of portfolio management<br />
model <strong>for</strong> prioritization<br />
Inputs<br />
Metrics<br />
POS<br />
Probability of technical & regulatory success (PTRS)<br />
Financing and country-level uptake<br />
Costs<br />
Development costs<br />
Implementation, including cost of goods sold (COGs)<br />
Value<br />
Public health impact (metric)<br />
“Strategic value”<br />
Saving lives &<br />
preventing<br />
disease<br />
Control<br />
& elimination<br />
Public health impact: Cases or deaths averted<br />
Strategic value: Metric<br />
22
Cost<br />
Low<br />
High<br />
A commercial-sector model <strong>for</strong> prioritization:<br />
Portfolio management<br />
Inputs<br />
Metrics<br />
Low<br />
High<br />
Probability of Success<br />
(POS)<br />
Bubble Area is proportional to NPV<br />
POS<br />
(Risk)<br />
Costs<br />
Value<br />
Probability of Technical &<br />
Regulatory Success<br />
(PTRS)<br />
Commercialization Risk<br />
Highly sensitive to assumptions<br />
Development costs<br />
Commercialization,<br />
including cost of goods<br />
sold (COGs)<br />
Assumptions = Risk + Uncertainty<br />
Net Present Value<br />
(Discounted Cash Flow)<br />
“Strategic Value”<br />
23
Probability of<br />
technical & regulatory<br />
success<br />
(PTRS)<br />
24
Sources and management of uncertainty and risk<br />
in <strong>vaccine</strong> <strong>development</strong> (PTRS + commercial opportunity)<br />
Sources of uncertainty and risk in <strong>vaccine</strong> <strong>development</strong><br />
Biological Technical (R&D) Commercial<br />
Immunity<br />
Safety/<br />
Tolerability<br />
CMC Clinical Regulatory<br />
Disease<br />
burden<br />
Payor<br />
policy<br />
Health care<br />
provider<br />
Competition<br />
/future trends<br />
Pathogen Uncertainty --- --- Uncertainty Uncertainty Uncertainty --- --- ---<br />
Vaccine Uncertainty Uncertainty Both Risk Both Both Both Both Both<br />
= Mainly uncertainty = Mainly risk = Both uncertainty and risk<br />
Biological<br />
Malaria <strong>vaccine</strong>s<br />
Technical (R&D)<br />
Strategic<br />
goal<br />
Immunity<br />
Safety/<br />
Tolerability<br />
CMC Clinical Regulatory<br />
Uncertainty --- --- Uncertainty Uncertainty<br />
Vaccine Uncertainty Uncertainty Both Risk Both<br />
25
Sources and management of uncertainty and risk<br />
in <strong>vaccine</strong> <strong>development</strong> (PTRS)<br />
Strategic<br />
goal<br />
Biological<br />
Immunity<br />
Malaria <strong>vaccine</strong>s<br />
Safety/<br />
Tolerability<br />
Technical (R&D)<br />
CMC Clinical Regulatory<br />
Uncertainty --- --- Uncertainty Uncertainty<br />
Vaccine Uncertainty Uncertainty Both Risk Both<br />
<strong>Prioritizing</strong> through<br />
defining/managing<br />
uncertainty<br />
26
<strong>Prioritizing</strong> through defining/managing uncertainty:<br />
controlled human <strong>malaria</strong> infections<br />
Experimental medicine<br />
Translational<br />
research<br />
Challenge<br />
model(s)<br />
Product <strong>development</strong><br />
Translational<br />
<strong>development</strong><br />
Challenge<br />
model(s)<br />
Phase1<br />
Control<br />
Vaccine 1<br />
Vaccine 2<br />
Infected mosquitoes<br />
Aseptic sporozoites<br />
Blood-stage parasites<br />
Time after challenge<br />
27
Translational research product <strong>development</strong><br />
learn-confirm* (+ apply) paradigm<br />
*Sheiner, 1997<br />
Learn* Confirm* Apply<br />
Translational<br />
<strong>development</strong><br />
Product <strong>development</strong><br />
Late-stage<br />
<strong>development</strong><br />
Post<br />
approval<br />
Challenge<br />
model(s)<br />
Phase1 Phase 2 Phase 3 File Phase 4/5<br />
Experimental medicine<br />
Translational<br />
research<br />
Challenge<br />
model(s)
Summary<br />
• There is an ongoing need to prioritize the global <strong>malaria</strong><br />
<strong>vaccine</strong> pipeline.<br />
• Updating the Malaria Vaccine Technology Roadmap (T-2013)<br />
serves to maintain a shared Vision, Strategic Goals, and<br />
Landmarks <strong>for</strong> <strong>development</strong> of <strong>malaria</strong> <strong>vaccine</strong>s.<br />
• A portfolio management approach is likely the most efficient<br />
and effective way to deploy limited resources.<br />
• Leveraging the Controlled Human Malaria Infection models in<br />
Translational Research and Translational Development in a<br />
Learn-Confirm-Apply paradigm enables defining and<br />
managing the uncertainty in the high-risk endeavor of<br />
developing <strong>malaria</strong> <strong>vaccine</strong>s.<br />
29
For more in<strong>for</strong>mation:<br />
www.<strong>malaria</strong><strong>vaccine</strong>.org<br />
www.path.org<br />
Thank you
Change language