Progress in malaria vaccine development

Christian Loucq, MDDirector, PATH Malaria Vaccine Initiative

Brussels / 17 March 2011

Update on progress

Social Affairs Committee, EU-ACP Joint Parliamentary Assembly

2

Malaria’s reach and retreat

3

Malaria’s reach in Africa

Statistics for 2009 (WHO):• 225 million cases (world)• 781,000 deaths (world)

• >80 percent of deaths are toyoung children in Africa

4

Why a vaccine?

Data as of the end of 2008, WHO

Vaccines are responsible for the prevention and control of at least 19 major human diseases, including smallpox, whooping cough, poliomyelitis, and measles.

5

Tools for malaria control

Safe and effective treatment (ACT)

Intermittent preventive treatment (IPT) - Pregnancy / infants / children

Insecticide treated bednets (ITNs)

Indoor residual spraying (IRS)

RDTs

6

The major challenges to success

Commercial

• Limited market in developed countries

• Malaria-endemic countries mostly poor

• Vaccine development is high-risk, high-cost

Scientific

• No vaccine in human use against a parasite

• Malaria parasite has ~6,000 genes, many more than a virus

• How to predict a vaccine candidate’s success?

7

The development of a malaria vaccine

• Challenging, but…

• Possible:• Individuals living in endemic regions acquire natural immunity against disease

• Experiments in the 1970s showed possibility of immunization (humans immunized by radiation-treated mosquitoes)

• First experiments at WRAIR

A malaria vaccine would be an essential componentof future malaria prevention and control measures

8

PATH Malaria Vaccine InitiativeTo accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world

A world free from malaria

9

• Since 2003, MVI has…• Advanced 10 projects into Phase 1 studies,• Advanced 5 into Phase 2a challenge studies

• In 2010…• 3 MVI-supported vaccine projects have

been in clinical development, including RTS,S• A fourth project is expected to enter the clinical

phase in early 2011.

• MVI has made possible significant progress in developing and refining evaluation technologies that allow malaria vaccine researchers to assess vaccine approaches in vitro

• And RTS,S

Progress, despite challenges

10

• RTS,S: first vaccine candidate to demonstrate that it can protect young children against clinical disease and infection caused by Plasmodium falciparum…

• RTS,S has demonstrated efficacy in different transmission settings (Kenya, Mozambique, Tanzania);

• 50% of malaria cases can be expected to be averted• Beneficial effect on clinical and severe disease up to

42 months after last vaccine dose• Trend toward higher efficacy again severe disease

• Acceptable reactogenicity and safety profile

• Can be co-administered with routine EPI immunizations

Progress, despite challenges

11

Phase 3 efficacy trial

(1) Age at f irst dose(2) ClinicalTrials.gov web site. Ef f icacy of GSK Biologicals' Candidate Malaria Vaccine 257049 Against Malaria Disease in Infants and Children in Africa. Available f rom: http://www.clinicaltrials.gov/ct2/show/NCT00866619?term=phase+III+malaria+vaccine&rank=2 [Accessed: 11 June 2009](3) MARA & ARMA web site. Maps. Map adapted f rom “Duration of Malaria Transmission Season”: http://www.mara.org.za/ [Assessed: 11 June 2009]

Enrollment complete: 15,461 children

11

• First vaccinations on May 26, 2009, in Bagamoyo, Tanzania

• 11 centers in 7 African countries with different transmissions settings

• Malaria control measures optimized

• Key safety & efficacy data to support file for regulatory authorities; trial ends at end-2013

• Significant capacity building investment

• Designed in collaboration with MVI and the Clinical Trials Partnership Committee, with feedback from WHO, FDA, EMA and NRAs

12

2009 2010 2011 2012 2013 2014 2015 2016Q3 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

Phased availability of Phase 3 efficacy data

Phase 3 efficacy study

Children 5-17 months

12 M post dose 3

Infants 6-12 weeks, EPI

12 M post dose 3

Public health efficacy endpoints in both

age-groups32 M- post dose 3

13

• Accelerate development of vaccines• Clinical disease and death caused by Pf and Pv• Develop Pf and Pv vaccines to support global

elimination and eradication effort

• Ensure clear development strategies• Manufacturing• Preclinical and clinical development • Regulatory• Policy

Overall R&D strategy

Parasite burden is dependent on lifecycle stage being targeted

14

<50

~100,000,000,000

<5

15

Prime-boost

16

Interrupt Reducelifecycle transmission

Transmission blocking vaccines

Elimination

17

What is needed?

• Early preparation to help close the gap between vaccine availability and use

• Investments in next-generation vaccines targeting elimination and eradication….

• Passion, strategy, partners, and support

Christian Loucq, MDDirector, PATH Malaria Vaccine Initiative

Brussels / 17 March 2010

Thank youFor more information:www.malariavaccine.orgwww.path.org

Social Affairs Committee, EU-ACP Joint Parliamentary Assembly