APPMG BEAD meeting London, February 6, 2006

MALARIA VACCINES DEVELOPMENT:

THE WAY AHEAD

Joe Cohen, Ph.D.Vice President R&DVaccines for Emerging Diseases & HIV

APPMG BEAD meeting London, February 6, 2006

GSK: A global Vaccine GSK: A global Vaccine CompanyCompany

Global vaccine supplier

1.6 billion doses of GSK vaccines distributed in over 168 countries

90% of total volume went to the Developing World

Primary supplier to WHO, UNICEF, PAHO, GAVI

APPMG BEAD meeting London, February 6, 2006

Combination vaccines facilitating delivery and compliance e.g. Tritanrix: D, T, Pw, HepB, Hib

Meningitis vaccines aimed at Africa’s “Meningitis belt” e.g. MenACW; Hib MenAC

Rotarix early introduction in international markets based on medical needs

R&D on new vaccines for which primary or exclusive need is in DCs, e.g. Malaria, TB, HIV

GSK Vaccine Programs GSK Vaccine Programs addressing the needs of the addressing the needs of the

Developing WorldDeveloping World

APPMG BEAD meeting London, February 6, 2006

Vaccine Research & DevelopmentVaccine Research & Development

Identify Antigens

Produce Antigens

Test in Animals

Proof of Concept

Phase I III File

x

Registration/Post marktng

xup to 10-20M$ up to 50-100M$ up to 500-1B$

x x 1-10 yrs 2-3yrs 2-4 yrs 1 yr

x

Transfer Process to Manufacturing

Build Facility

II

Research (inc. Immunology)

Preclinical Development (inc. Formulation Science)

Clinical Development (inc Post Marketing Surveillance

APPMG BEAD meeting London, February 6, 2006

84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04

2 17

14 16 20 21

23

Studies in The Gambia

1

3 6 8 10

Rec E. coli based strategies

RTS,S studies in Non-immunes (US/EU)

9 11 12 1513 18 195 7

R16HBs

RTS,S adjuvant studiesPreclinical and CMI studies

CS cloned,sequenced

SKF/WRAIRCRDA

Program Transferred to Rixensart

GSK/MVIPartnership

4

Program led by SKF/SB Phila

Program led by SB/GSB Bio Rix

Hashed = preclinical ; Solid = clinical

GSK publications ; Key POC studies in green

A Brief History of the GSK Bio Malaria Vaccine Program

22

Studies in Mozambique 24

APPMG BEAD meeting London, February 6, 2006

Pediatric CDP for RTS,S/AS02A up Pediatric CDP for RTS,S/AS02A up to PoCto PoC

In partnership with PATH-MVIIn partnership with PATH-MVI

2001 2003 20042002

Ph I 6-11 yrsDose range

Ph I 6-11 yrsDose range

Ph I 1-5 yrsDose rangePh I 1-5 yrsDose range

Ph I Safety 1-4 yrs

Ph I Safety 1-4 yrs

½ adult dose

selectedPhase IIb Efficacy

1-4 yrs with long term F/U

Gambia

Mozambique

2005

Unblinding

APPMG BEAD meeting London, February 6, 2006

Summary of results from the Summary of results from the LandmarkLandmark

PoC Study in Mozambique*PoC Study in Mozambique*

Vaccine is safe and well tolerated in 1-4 year old children

Efficacy against uncomplicated malaria: 35%

Efficacy against severe malaria disease: 50%

Protection persists for at least 18 months

* P. Alonso et al, Lancet, 364:1411-20 , 2004* P. Alonso et al, Lancet, 366:2012-18, 2005

APPMG BEAD meeting London, February 6, 2006

Significance of the resultsSignificance of the results

Represent a major scientific breakthrough

Estimated vaccine efficacy is comparable to that of existing or contemplated malaria preventive methods (eg. insecticide impregnated bed nets, indoor spraying, IPTi)

If efficacy confirmed in subsequent clinical evaluation

This vaccine will have a significant public health impact

APPMG BEAD meeting London, February 6, 2006

The Way Forward: Clinical The Way Forward: Clinical Development PlanDevelopment Plan

Establish Safety in infants

– staggered with other EPI vaccines: 2005-06

Establish Safety and compatibility with current EPI vaccines and PoC in infants

– in co-administration with EPI vaccines: 2006-07

Multi-centric Phase III (Efficacy) in Africa (2008-2009)

Process scale-up and build Industrial scale Manufacturing facility (2005-2008)

File submission: 2010

APPMG BEAD meeting London, February 6, 2006

WHAT NEEDS TO BE DONE WHAT NEEDS TO BE DONE OVEROVER

THE NEXT 4 YEARS IN ORDER THE NEXT 4 YEARS IN ORDER TO AVOID ANY DELAYS IN TO AVOID ANY DELAYS IN VACCINE DEPLOYEMENTVACCINE DEPLOYEMENT

APPMG BEAD meeting London, February 6, 2006

Prepare for introductionPrepare for introduction

Implementation of the Clinical Development Plan (GSK, PATH-MVI, Collaborators)

Production scaling-up and manufacturing facility built and validated (GSK)

Regulatory strategy developed (GSK, MVI-PATH, European Reg. Authorities, WHO, National Reg. authorities)

Implementation strategy: integration with EPI and with other malaria control measures [GSK and partners, International Health Authorities (WHO, UNICEF) and National Heath Authorities]

APPMG BEAD meeting London, February 6, 2006

Accelerate IntroductionAccelerate Introduction

Create demand Advocacy

Demand Forecasting

Identify funding sources and mechanisms GAVI, The Global Fund

Advance Purchase Commitments

Important at beginning of Phase III clinical development

Financial under pinning for decisions on manufacturing facilities

Guaranteed number of doses to be purchased

Coordinated strategy between public and private sector

APPMG BEAD meeting London, February 6, 2006

CONCLUSIONS – Main MessagesCONCLUSIONS – Main Messages

An effective vaccine against malaria will become a reality in the short to mid-term future and possibly as early as 2010/2011

APPMG BEAD meeting London, February 6, 2006

CONCLUSIONS – Main MessagesCONCLUSIONS – Main Messages

It will need to be integrated into existing public health interventions (EPI vaccination, Malaria prevention measure) in endemic regions

APPMG BEAD meeting London, February 6, 2006

CONCLUSIONS – Main MessagesCONCLUSIONS – Main Messages

When the vaccine is available and registered, a rapid and broad introduction must be our common goal

APPMG BEAD meeting London, February 6, 2006

CONCLUSIONS – Main MessagesCONCLUSIONS – Main Messages

Now is the time to start planning for

– Manufacturing

– Regulatory Strategy

– Implementation policy

– Accelerated introduction

– Vaccine procurement mechanisms

APPMG BEAD meeting London, February 6, 2006

CONCLUSIONS – Main MessagesCONCLUSIONS – Main Messages

GSK is committed to achieving this goal through strong Partnership with Governments, NGO, International and National Health authorities and donor organizations