mmv · prof. michael ferguson, dr winston gutteridge, dr fatoumata nafo-traoré, dr robert newman,...

In 1999, MMV was a pioneering newcomer to the

world of antimalarial drug research. The World

Health Organization (WHO) was reporting more

than 300 million cases of malaria each year. The

malaria parasite had become resistant to widely-

used drugs. New medicines were desperately

needed as malaria continued to afflict and take

the lives of countless people across the world.

While the antimalarial market is huge in terms

of those in need, it is small in terms of profit.

By 1999, this imbalance had led to a virtually

empty pipeline of new antimalarial drugs.

Motivated by this glaring inequity and the need

to act in the face of a projected public health

disaster fuelled by escalating drug resistance, a

group of dedicated individuals and organizations

launched MMV. It started out modestly with only

USD 4 million in seed finance and three early-

stage projects in its portfolio, but was brimming

with ambition.

Today, 15 years on, this ambition has borne fruit.

By working in partnership with public and private

players, MMV has surpassed its original objective

to develop one new effective antimalarial before

the end of 2010. Since its foundation in 1999,

MMV and partners have developed and/

or registered four new medicines: Pyramax®,

(pyronaridine-artesunate) with Shin Poong;

Eurartesim® (dihydroartemisinin-piperaquine) with

Sigma-Tau; Artesun® (artesunate injection) with

Guilin; and Coartem® Dispersible (artemether-

lumefantrine) with Novartis.

Medicines for Malaria Venture and partners are working together to discover, develop and deliver new

effective and affordable antimalarials to give vulnerable populations a better chance of a healthy future,

and help ultimately eradicate this terrible disease.

Developing medicines, defeating malaria

Defeating Malaria Together

But we cannot stop there. To meet the ambitious

goal of malaria eradication, new medicines

with novel mechanisms of action are needed,

especially to fill the gap that might be left by

threats, such as resistance to artemisinin. We

also need new medicines to treat the most

vulnerable populations (children and pregnant

women), to cure relapsing malaria and to prevent

transmission.

As new medicines emerge from the pipeline,

MMV and partners collaborate to ensure that

they reach patients quickly and save lives.

With the largest-ever pipeline of antimalarial

molecules, MMV is set to develop and deliver

critical medicines for the ultimate eradication of

malaria.

AT AGLANCE

MMV

MMV shows how the market can work for the world’s poorest people.”Melinda Gates

Key achievements

Malaria Boxes 200dispatched to more than 30 countries since launch in December 2011, to catalyse malaria and neglected disease drug research.

Direct and in-kind support from our pharma partners more than trebling the value of each donor dollar for R&D.

=1 3.50USD USD

million treatments ofchild-friendlyCoartem®

Dispersible

250

( a r t e m e t h e r - l u m e f a n t r i n e ,

co-developed with Novart is) distributed to 50 countries since launch in 2009.

million

vials ofArtesun®

25(Guilin Pharmaceutical’s MMV-

supported injectable artesunate)

for severe malaria deliver-ed since 2010 – saving an est imated 165,000 additional lives compared to treatment with quinine.

enteredPhase IIItrialsin April 2014 – taking it closer to becoming the only new drug for relapsing malaria in over 60 years.

compounds 9targeting malaria eradi-cation, progressed from discovery to preclinical or clinical development.

new

MMV at a Glance 2014 I www.mmv.org

OZ439 together with piperaquine entered Phase IIB single-dose, combination studies in July 2014.

Tafe

noquin

e

MMV’s Product Development Partnership

(PDP) model has blossomed and born

fruit. By nurturing and strengthening

partnerships with clinicians and scientists

across academia and the pharmaceutical

industry, and combining this with rigorous

portfolio management, MMV has become

a highly cost-effective and productive

R&D organization. The model’s success

has created a virtuous circle that brings in

new donors and stakeholders.


The PDP model

Malaria...takes a child’s life every minute

kills ~627,000 people each year

– the vast majority are children

can kill within 24 hrs of symptom onset

can infect an African child up to

6 times a year

costs Africa USD 12-30 billion in lost

GDP every year

accounts for 40% of all public health

spending in Africa

is both a cause and consequence

of poverty

1. International Conference on Harmonisation of Technical

Requirements for Registration of Pharmaceuticals

for Human Use (ICH)

2. Good Laboratory Practice (GLP)

3. Good Clinical Practice (GCP)

4. Good Manufacturing Practice (GMP)

Over the years, MMV has worked in

partnership with more than 300 research

institutions and companies across the world.

Each partner brings expertise, enabling

technologies and research facilities, the value

of which often exceeds the funding received

from our donors.

In addition to innovative individual projects,

miniportfolios enable the efficient distribution of

resources that help to accelerate the discovery

of promising antimalarial compounds.

Meticulous selection processes are coupled

with support for the most promising candidate

drugs and quick termination of those that miss

milestones or do not meet MMV’s demanding

product profiles. This industry-style portfolio

management is not easy to execute but is

essential to maximise the use of every donor

dollar towards our highly-focused mission.

The innovative route to neglected disease drug development

Quality for allMMV strongly bel ieves that al l malaria

patients, rich or poor, deserve the best and

safest treatment possible. All new antimalarial

medicines co-developed by MMV must meet

high international standards, for example

those required by the European Medicines

Agency, the US FDA or WHO’s Prequalification

Programme. MMV and partners conduct

all clinical development projects to ICH1

guidelines every step of the way – from GLP2

standards for preclinical work, GCP3 standards

for clinical trials in malaria-endemic countries

that also adhere to national regulations, and

finally GMP4 standards during the manufacture

of the medicines.

Academic research and clinical trial sites

New medicines for malaria

Pharmaceutical research

Donors and in-kind contributions

MMV supported projects 4th quarter 2014Antimalarial drug discovery and development projects scientifically and/or financially supported by MMV.


ESAC Expert Scientific Advisory Committee

GSB Global Safety Board

MMV Board of Directors/Executive Committee/Financial Audit Committee

APMACAccess and Product ManagementAdvisory Committee

APAC Authorization for Phase III/Advancement Committee

Access andProduct

Management

GO

VE

RN

AN

CE

Research Translational Development APMLead

optimizationPreclinical Human

volunteersPatient

exploratoryPatient

confirmatoryUnder review

Novartis Miniportfolio

Novartis 1 project

GSK Miniportfolio

AstraZeneca Miniportfolio

GSK 3 projects

Sanofi Orthologue Leads

AnacorOxaboroles

Liverpool School of Trop Med/Univ. Liverpool Tetraoxanes

Univ. Texas Southwestern/ Monash Univ./ Univ. WashingtonDHODH

CelgeneHeterocycles

Univ. CampinasHeterocycles

Daiichi-Sankyo Screening

TakedaScreening

Univ. SydneyOpen Source Drug Discovery

EisaiScreening

Merck SeronoAmino-alcohols

Other projects 15 projects

P218 DHFRBiotec/ (Monash Univ./ LondonSchool of Hygiene & Trop Med)

DSM265Takeda/ NIH

Artemether- lumefantrinedispersible Novartis

Artesunate for injection Guilin

Dihydro-artemisinin- piperaquine Sigma-Tau

Pyronaridine-artesunateShin Poong

Artesunate- amodiaquine

Sanofi/ DNDi

Univ. Cape TownAminopyridines

OZ439/PQPSanofi

Research Translational Development APMLead

optimizationPreclinical Human

volunteersPatient

exploratoryPatient

confirmatoryUnder review Post

approval

Rectal artesunate Cipla/ Strides/WHO-TDR

*

MMV048Univ. Cape Town/ Technology Innovation Agency

OZ439/FQSanofi

MMV Pathogen Box

Artesunate- mefloquine

Cipla/ DNDi *

Tafenoquine GSK

Dihydro-artemisinin-piperaquinepaediatric Sigma-Tau

Pyronaridine-artesunatepaediatricShin Poong/Univ. Iowa

KAE609 Novartis

KAF156Novartis

SP+AQ(sulfadoxine-pyrimethamine + amodiaquine)

Guilin

MMV121(Univ. Dundee)

PA92(Drexel Univ./ Univ. Washington/ Genomics Institute of the Novartis Research Foundation)

MMV253(AstraZeneca )

GSK030GSK

SJ733St Jude/ (National Institutes of Health [NIH]/Rutgers Univ.)

TPP1 minimal essential: 3-day cure/artemisinin-based combination therapies

› Artemether-lumefantrine dispersible (Coartem® Dispersible), generic by Ajanta

› Dihydroartemisinin-piperaquine (Eurartesim®)

› Dihydroartemisinin-piperaquine paediatric (Eurartesim®)

› Pyronaridine-artesunate (Pyramax®)

› Pyronaridine-artesunate paediatric (Pyramax®)

› Artesunate-amodiaquine (CoarsucamTM, ASAQ/Winthrop®) FDC generics by Ajanta,

Ipca, Guilin and co-blistered generics by Strides & Cipla

› Artesunate-mefloquine, co-blistered generic by Acino/Mepha

Potential single-dose agents that could be combined into SERCaP

› OZ439/FQ

› OZ439/PQP

› KAE609

› KAF156

› Tafenoquine

Intermittent chemoprevention

› Sulfadoxine-pyrimethamine + amodiaquine (SP+AQ)

Severe malaria

› Rectal artesunate

› Artesunate for injection (Artesun®)

Fast clearance (TCP1)

Long duration (TCP2)

Relapse prevention (TCP3a)

Transmission blocking (TCP3b)

Chemoprevention (TCP4)

To develop the individual compounds for combination into the TPPs,

MMV has defined five Target Candidate Profiles (TCPs):

Non-artemisinin-based therapy

Artemisinin-based therapy

Bioequivalence studies planned in preparation for WHO prequalification

Included in MMV portfolio post registration

First review or approval by WHO Prequalification, or by regulatory bodies who are

ICH members or observers

The malaria community has defined two Target Product Profiles (TPPs) for medicines to make

eradication achievable: TPP1: a treatment combination that is ideally a Single Exposure Radical

cure and Prophylaxis (SERCaP) and TPP2: Single Exposure Chemoprotection (SEC).

Target Product Profiles and Target Candidate Profiles

Postapproval

1. To support new drug introduction, MMV

provides product briefings to policy decision

makers, and creates simple, understandable

packaging and training materials. For exam-

ple, in 2013 and 2014, MMV and partners,

Clinton Health Access Initiative and Malaria

Consortium, signed agreements with five of

six malaria-endemic countries, in which we

will scale-up the use of injectable artesunate

to treat severe malaria, with funding from UNI-

TAID. This programme also allows MMV to

support pharmaceutical partners to develop a

WHO-prequalified artesunate suppository for

pre-referral treatment of severe malaria.

2. MMV has pioneered new initiatives to

enhance the reach of new medicines via

the public and private sector. Our Consortium

for ACT private sector subsidy (CAPSS) ini-

tiative in Uganda first established key private-

sector subsidy principles, including that a

subsidy leads to a significant increase in the

use of ACTs. The principles were later em-

ulated in the Affordable Medicines Facility

for Malaria (AMFm) and are now a standard

option provided by the Global Fund via the Pri-

vate Sector Co-payment Mechanism.

3. Monitoring the uptake of quality medi-

cines is critical for MMV. We gather market


16 countries85 partnerships




Working in partnershipSince its inception, MMV has successfully worked in over 50 countries with more than 300 partners from the public and private sectors,

from NGOs and non-profit organizations, as well as from clinical trial sites.

Access for health impactMMV’s Access and Product Management (APM) team focuses on four key areas to ensure new antimalarials reach people in need:

intelligence on how new medicines are pro-

cured and ultimately reach patients. Key work

includes SMS for Life in Tanzania, where mobile

technology was used to track drug availabili-

ty, and our collaboration with IMS to routinely

gather data on antimalarial flow into Zambia.

4. The APM team’s engagement with the

“voice of countries” also helps us shape

our R&D work. For example, market research

has evaluated the acceptability of different

product presentations and is guiding critical

formulation decisions for single-dose cures

currently in development. Separately, APM is

supporting the development of a new complete

cure for relapsing malaria by documenting

current practices and attitudes regarding such

treatment.

By working hand-in-hand with MMV’s science

team and partners, APM ensures that MMV

will develop highly effective medicines that

respond to the evolving needs of malaria

patients and the marketplace.

GATHERING MARKETINTELLIGENCE

SUPPORTING INTRODUCTION

ENHANCINGREACH

INFORMINGR&D

GOAL:

Minimise time-to-market

for newly registered MMV

medicines in priority

countries.

GOAL:

Ensure timely availability

of key market data to inform

product development and

launch, and measure impact.

GOAL:

Expand access to

medicines, through existing

and innovative channels to

improve availability.

GOAL:

Help align product

development criteria with

unmet medical needs.

Board of DirectorsMr Ray Chambers (Chairman), Dr Pedro Alonso,

Dr David Brandling-Bennett, Dr Ernest Darkoh,

Prof. Michael Ferguson, Dr Winston Gutteridge,

Dr Fatoumata Nafo-Traoré, Dr Robert Newman,

Dr David Reddy, Dr Dennis Schmatz and Mr Per

Wold-Olsen.

MMV North America Inc. Board MembersDr Dennis Schmatz (President of the Board of

North America Inc.), Dr David Bowen, Mr Ray

Chambers, Dr David Reddy and Ms Wendy Taylor.

Expert Scientific Advisory Committee (ESAC)Dr David McGibney (Co-chairman, Development),

Dr Dennis Schmatz (Co-chairman, Discovery), Dr

Aileen Allsop, Dr Salim Abdullah, Prof. Kelly Chibale,

Dr Robert Clay, Prof. Simon Croft, Prof. Umberto

D’Alessandro, Prof. Ogobara Doumbo, Dr Michael

Dunne, Prof Paul Fish, Dr Kasturi Haldar, Prof Dennis

Kyle, Dr Trevor Laird, Prof John Lambert, Dr Mary

Mader, Dr Michael Makanga, Dr Christine Manyando,

Dr George K Mooney, Prof. François Nosten, Dr

Bernhards Ogutu, Dr Paul Reider, Dr David Roberts,

Dr Peter Siegl, Dr Per Sjoberg, Prof. Dennis Smith,

Prof. Terrie Taylor, Dr Neena Valecha, Dr Thomas

Wellems and Dr Matthew Wyvratt.

Access & Product Management Advisory Committee (APMAC)Prof. Christian Lengeler (Chairman), Dr Neena

Valecha (Vice Chairman), Ms Valentina Buj,

Dr Elizabeth Chizema, Dr Graciela Diap,

Dr Alexander Dodoo, Dr Gunther Faber,

Dr Douglas Lungu, Dr David McGibney,

Prof. Ric Price, Ms Melanie Renshaw,

Dr Claude Emile Rwagacondo, Dr Richard

Steketee, Prof. Andy Stergachis and

Dr Brenda Waning.

MMV TeamNada Abla Geiser, Marc Adamy, Nada Araeipour,

Adam Aspinall, Jaya Banerji, Chris Barker, Lidiya

Bebrevska, Soazig Bertrand, Benjamin Blasco,

Grégory Bonnaud, Isabelle Borghini-Fuhrer, Emilie

Burlot, Jeremy Burrows, Andrea Buscaglia, Brice

Campo, Stephan Chalon, Stéphanie Cherbuin, Marion

Colombani, Maud Couturier, Gelavizh Daghigh, Helen

Demarest, Heidi Divecha, Christina do Paço, Matthew

Doherty, Cristina Donini, Celia Doudou, Stephan

Duparc, Mélanie Dupuy, Myriam El Gaaloul, Isabelle

Fontaine, Sylvie Fonteilles-Drabek, Penny Grewal

Daumerie, Joan Herbert, Pierre Hugo, George Jagoe,

Alexis Kamdjou, Sonia Kanobana, Franziska

Karyabwite, Wiweka Kaszubska, Coline Legrand,

Didier Leroy, Andrea Lucard, Antonia Lundquist,

Adrienne MacDonald, Fiona Macintyre, Maud Majeres

Lugand, Neil McCarthy, Aleksandra Misiorowska,

Jörg Möhrle, Alicja Poczatenko, Elizabeth Poll, Anya

Ramalho, Elena Ramos, David Reddy (CEO), Emilie

Rossignol, Mélanie Rouillier, Marie-Ange Roustan,

Thomas Rückle, Binetou Sané, Sonia Schnieper

Samec, Thomas Spangenberg, Tareq Sunderji,

Yuko Takase, Simona Valigova, Wesley van Voorhis,

Helen Weir, Tim Wells and Paul Willis.

Editors: Elizabeth Poll and

Jaya Banerji

Photos: MMV (cover a & p 4c),

Merck Serono (cover b),

BMC St Jude (p 1) and Séverine Pillet (p 4a)

Jennifer Jackson (p 4b)

Designer: ComStone-Pierre Chassany

Medicines for Malaria Venture (MMV) International Centre Cointrin

Route de Pré-Bois 20 - PO Box 1826

1215 Geneva 15 - Switzerland

T + 41 22 555 03 00 - F + 41 22 555 03 69

www.mmv.org | [email protected]

Focus on finances Medicines for Malaria Venture receives

s u s t a i n e d f u n d i n g a n d s u p p o r t

f rom government agencies, pr ivate

foundations, international organizations,

corporations, corporate foundations

and private individuals. These funds are

used to finance the MMV portfolio of R&D

projects as well as specific, targeted

access and delivery interventions that

aim to make it easier for vulnerable

populations to access MMV products.

In 2013, MMV secured significant funding

commitments of USD 238 from four major

donors. This success, founded on our

donors’ firm belief in MMV’s vision and ability

to realise it, continued into 2014. In the

first 10 months of 2014, the Bill & Melinda

Gates Foundation and the United Kingdom’s

Department for International Development

(DFID) pledged an additional USD 40 million

to support MMV’s work.

Nevertheless, this still leaves a shortfall over

the next 5 years to sustain the portfolio and

advance towards the goal of elimination and

eradication. Progress is dependent on the

availability of long-term funding.

Figure 1 Sources of funding from 1999 to 2018

Project-Related R&D 77.0%

Access & Product Management 9.4%

External Relations & Advocacy 4.1%

Governance & Stakeholders 0.2%

Management & Administration 9.3%

Figure 2 MMV expenditure 2013: USD 65.2 million

Public and private investments need to

increase to support MMV’s discovery,

development and delivery of next-generation

antimalarials to help eradicate malaria.

As a result, MMV is striving to expand

and develop current and new donors and

negotiate the best terms with our partners.

Bill & Melinda Gates Foundation 62.87%

United Kingdom’s Department for International Development (DFID) 15.99%

Wellcome Trust 3.66%

United States Agency for International Development (USAID) 2.93%

Netherlands Minister for Development Cooperation 2.21%

Irish Aid 2.14%

Swiss Government SDC 2.13%

National Institutes of Health (NIH) 1.48%

Spanish Agency for International Development 1.36%

World Bank 0.96%

Rockefeller Foundation 0.72%

ExxonMobil Foundation 0.72%

World Health Organization/Roll Back Malaria (WHO/RBM) 0.67%

Global Health Innovative Technology Fund (GHIT) 0.46%

UNITAID 0.43%

Newcrest Mining Limited 0.41%

Norwegian Agency for Development Cooperation (Norad) 0.35%

Australian Government Department of Foreign Affairs and Trade (DFAT) 0.30%

BHP Billiton 0.09%

MerckSerono 0.06%

Individual donors 0.05%

EU CRIMALDDI 0.01%

© November 2014 Medicines for Malaria Venture - All rights reserved

mmv · prof. michael ferguson, dr winston gutteridge, dr fatoumata nafo-traoré, dr robert newman,...

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