GSK’s Commitment to Malaria

Didier Lapierre

Vice President, Head of Global Clinical Development Centre for Early Development and DDW Vaccines

All Party Parliamentary Malaria Group Meeting 8 July 2008

A Global Company Committed to the Diseases of the Developing World

GSK is the only company with drugs and vaccines in development for the Big Three killer diseases: AIDS, TB and malaria

In 2007 we provided 85 millions epivir-combivir tablets and our licencees 183 millions tablets

More than 3 million doses of GSK Bio’s vaccines are distributed every day to 169 countries

Close to 80% of vaccine doses go to the developing world

Ranked #1 on the first ever Access To Medicines Index(2008)

Prevention

Treatment

Advocacy and mobilising support

Vaccine Development

Drug Development

Philanthropy and Community Engagement

GSK’s Has a Comprehensive Approach to Malaria

GSK DDW Drug Discovery CentreTres Cantos

122 Scientists with expertise in Drug Discovery

Partly supported by MMV, TB Alliance and DNDi

Supported by world-wide GSK R&D

ID CEDD Management Team and scientists

MDR, Preclinical and clinical development

GSK Site services

8,500 m2 of research facilities, including two P3 facilities, for in vitro (220 m2) and in vivo (4,000 m2) experimental work

TuberculosisMalariaOther DDW Neglected Diseases

Tres Cantos

GSK DDW Drug Discovery PipelinePortfolio in 2008

Target to Lead Lead to Candidate Candidate to PoC Post-PoC andLaunched

Malarone

Halfan

Zentel

Pentostam

sitamaquine

P IIItafenoqui

neP III

GSK antimicro

DHODH

GSKantimicro Pleuros

InhA

MGIFalcipainPyridone

BU

PyridoneGW932121

IsoquineGSK369796

Malate synthase

Macrolides

GSK-DDW Drug Discovery Partnerships

Major Partnerships

Targets and projects

Tools and Know-How

African Malaria PartnershipAfrican Malaria PartnershipThree projects to address education and behavioural change in African Three projects to address education and behavioural change in African communities communities

““Credit with Education” - Freedom from HungerCredit with Education” - Freedom from Hunger

Teaching village women about malaria prevention and treatment in Teaching village women about malaria prevention and treatment in 6 countries in West Africa6 countries in West Africa

““Ugandan Malaria Partnership” – AMREFUgandan Malaria Partnership” – AMREF

Training community health workers to deliver home based Malaria Training community health workers to deliver home based Malaria treatment to children and pregnant womentreatment to children and pregnant women

““Malaria prevention and Treatment” – Plan Int’lMalaria prevention and Treatment” – Plan Int’l

Behaviour promotion to prevent Malaria and treatment programme Behaviour promotion to prevent Malaria and treatment programme in White Nile State, Sudanin White Nile State, Sudan

Photographs: © KarlGrobl.com & Malaria Consortium

Mobilising for MalariaMobilising for MalariaA project of the GlaxoSmithKline African Malaria Partnership implemented A project of the GlaxoSmithKline African Malaria Partnership implemented by The Malaria Consortium by The Malaria Consortium

Purpose Purpose

““To strengthen capacity in the north and Africa to mobilise political To strengthen capacity in the north and Africa to mobilise political

support and increase resource allocations for malaria”support and increase resource allocations for malaria”

In Africa: In Africa: Focus on countries where strengthened Focus on countries where strengthened partnerships & political support needed partnerships & political support needed - Cameroon, Benin and Ethiopia- Cameroon, Benin and Ethiopia

In Europe: In Europe: Focus on countries with strong links to AfricaFocus on countries with strong links to Africa - UK, France and Belgium- UK, France and Belgium

Photographs: Photographs: © KarlGrobl.com & Malaria Consortium© KarlGrobl.com & Malaria Consortium

GSK’s Malaria Vaccine – The objective

Compatible with standard EPI vaccines(DTPw , HBV , Hib, OPV…)

Complements existing malaria control measures

A vaccine that will protect infants and young children residing inmalaria endemic regions from clinical disease and severe malaria resulting from Plasmodium Falciparum infection

Safe and well-tolerated

Implementable through existing delivery programs such as the EPI

85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07

History and Major Milestones of the RTS,S/AS Program

Proof of Concept in

Gambian adults (MRC)

GSK/MVIAgreement

Proof of Concept in

challenge model (WRAIR)

Start of the programin Belgium

Proof of Concept in

children(CISM)

Proof of Concept in

infants (CISM)

Key efficacy data in young Africa children and infants

CISM (Manhiça, Mozambique)

N ~2000, 1-4 years old

Safe and well tolerated

Highly immunogenic to CSP and HBSAg

Alonso et al, Lancet 2004; 364:1411-20

Alonso et al, Lancet 2005, 366:2012-18

clinical malaria: 35.3% (95% CI 22-47; p < 0.0001) 18 m FU severe malaria: 48.6% (95% CI 12-71; p = 0.02) 18 m FU hospitalized malaria: 30.5% (95% CI 4-50; p = 0.032) 18 m FU infection: 44.9% (95% CI 31-56; p < 0.001) 6 m FU

Vaccine efficacy in Infants 10 weeks old (Lancet 2007, 370:1543-51)Infection : 65% 3m FUClinical malaria : 65% 3m FU N~200

Limited Serious Adverse Events [0 - 45m]

n % ( 95% CI ) n % ( 95% CI )SEVERE MALARIA DISEASESerious Adverse events 235 326Cerebral malaria 2 0.2 0.0-0.7 4 0.4 0.1-1.0Severe malaria anemia 12 1.2 0.6-2.1 15 1.5 0.8-2.4Severe malaria (others) 37 3.7 2.6-5.0 58 5.7 4.4-7.4

MORTALITYAll deaths 12 1.2 22 2.2Excluded Trauma 11 1.1 18 1.8Malaria deaths 1 0.1 5 0.5

(n=1010)(n=1012)RTS,S/AS02A Control vaccines

Further indications of potential public health benefits

Sacarlal et al presented at ASTMH 2007

1.4-3.31.0-2.80.1-1.1

0.6-1.20.5-1.90.0-0.5

23 21-26 32 29-35

Clinical Trial Partnerships for RTS,S/AS

Northern Academic Institutions:• Prince Leopold Institut of Tropical Medicine, Belgium

• University of Copenhagen, Denmark

• University of Tuebingen, Germany

• Bernhard Nocht Institute, Germany

• University of Barcleona, Spain

• Swiss Tropical Institute, Switzerland

• London School of Hygeine and Tropical Medicine, UK

• US Centers for Disease Control and Prevention, USA

• Univeristy of North Carolina at Chapel Hill, USA

• Walter Reed Army Institute of Research, USA

Southern Academic Institutions:• Institut de Recherche en Science de la Sante, Burkina Faso

• Kumasi Centre for Collaborative Research and School of Medical Sciences Kumasi, Ghana

• Kintampo Health Research Centre, Ghana

• Albert Schweitzer Hospital, Gabon

• Kenya Medical Research Institute, Kenya

• Wellcome Collaborative Research Programme, Kilifi, Kenya

• University of North Carolina Project, Malawi

• Centro de Investigacao em Saude de Manhica, Mozambique

• Ifakara Health Research Development, Tanzania

• National Institute of Medical Research, Tanzania

Phase III Efficacy Trial

11 centers in 7 countries representing different transmission settings, launching late 2008/early 2009

Up to 16,000 children in 2 age categories:

6 weeks to 12 weeks (6,000 minimum)

5 to 17 months (6,000 minimum)

Designed to provide

Key safety and efficacy data to support file

Full evaluation of relevant disease and public health endpoints to inform implementation planning

If efficacy is confirmed in Phase III, the RTS,S/AS vaccine could have a major public health impact

Development Partnerships

PATH/MVI’s mission is to accelerate the development of promising malaria vaccines and ensure their availability and accessibility in the developing world.

The Bill & Melinda Gates Foundation's global health mission is to help to ensure that lifesaving advances in health are created and shared with those who need them most.

The Walter Reed Army Institute for Research was where the first breakthrough in the development of RTS,S was made. It was through our partnership with WRAIR that RTS,S/AS has grown into a viable vaccine candidate.

Partnering for Full & Rapid Access to a Malaria VaccineScaling Up for Production: GSK has spent more than 24 years and US $300m on developing a malaria vaccine, and building a manufacturing facility.

Unprecendented, Streamlined Regulatory Strategy GSK, MVI-PATH, European Reg. authorities, WHO, African national regulatory authorities

Implementation Strategy: Integration with EPI and other malaria control measures GSK and partners, international health authorities (WHO, UNICEF, GAVI) and national heath authorities

GSK Bio Rixensart, Belgium

Synergy with Other Interventions?

Infectious mosquito Infection of liver

Parasitemia

50% (95% CI 8 to 73) Schellenberg D et al., Lancet 2001; 357:1471IPTi

ITN

45% (95% CI 20 to 63) Lengeler C, Cochrane Database Syst Rev 2004

49% (95% CI 12 to 71) Alonso P et al.,Lancet 2005; 366:2012

RTS,S

Efficacy against Severe Malaria

Clinical episodes Severe Malaria

A Malaria Vaccine That Sits On the Shelf Is Useless

We Must Act NOW to Be Sure It Will Be Available and Widely Implemented As Soon As Possible