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Transcript
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
Priority Medicines For Europe and the World
"A Public Health Approach to Innovation"
Background Paper for Review
Public-Private Partnerships for Neglected Diseases:
Opportunities to address pharmaceutical gaps for
neglected diseases
CASE STUDY 1
Medicines for Malaria Venture (MMV)
By Elizabeth Ziemba, JD, MPH
7 October 2004
8.1 CS1-1
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
Case Studies and Needs Assessment of Four Public-Private Partnerships
Medicines for Malaria Venture (MMV)
Introduction:
The Medicines for Malaria Venture is a nonprofit foundation (501(c) 3
equivalent) focused on the delivery, development and registration of new
medicines for the treatment and prevention of malaria in disease endemic
countries. Founded in 1999 and headquartered in Geneva, MMV receives
public and philanthropic funding to support the drug discovery and
development efforts of its partners in academia and the pharmaceutical
industry.1
History of Medicines for Malaria Ventures
MMV was established by the founding partners, the World Health
Organization (WHO) and the International Foundation of Pharmaceutical
Manufacturers Association (IFPMA) and originally operated under the
umbrella of the WHO “Roll Back Malaria” program.Error! Bookmark not
defined. MMV was created because the increased cost of developing and
registering pharmaceutical products, coupled with inadequate return on
investment, have resulted in the withdrawal of the majority of pharmaceutical
companies from focusing resources to fund research and development on
malaria.Error! Bookmark not defined.
In addition to the lack of investment in research and development needed to
produce antimalarial medicines, the existing drugs for treating and controlling
the symptoms of malaria are losing their effectiveness as the malaria parasite
as transmitted by mosquitoes builds up resistance.Error! Bookmark not
defined.
The combination of the two factors, lack of investment in the basic science
needed to produce antimalarial medicines and the growing ineffectiveness of
current medicines to treat people in endemic countries, have created the
current public health care crisis.
Mission:
The Mission of the non-profit public-private partnerships, Medicines for
Malaria Venture, is:
To bring public, private and philanthropic sector partners together to fund
and manage the discovery, development and registration of new medicines
for the treatment and prevention of malaria in disease-endemic countries.2
8.1 CS1-2
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
Stated slightly differently, the 2002 Annual Report indicates that:
“Medicines for Malaria Venture is a nonprofit foundation dedicated to
reducing the burden of malaria in disease endemic countries by discovering
new affordable antimalarial medicines through effective public-private
partnerships”.1
The organization seeks to accomplish its mission by discovering, developing
and commercializing antimalarial medicines at prices that are affordable to
the populations living in endemic countries. MMV aims to develop one new
product every five years.1 3
According to its Business Plan for 2003-2007, MMV employs a threecomponent integrated strategy to achieve its mission:
1. Focuses predominantly on drug discovery and development through
portfolio management;
2. Interfaces with global health actors on up and downstream activities to
achieve health impact.
3. Conducts supporting activities, prioritizing communications and
fundraising.
Disease Rationale:
The worldwide resurgence of malaria has been extensively documented, and
with 300-500 million cases occurring each year it is likely that more people are
infected with malaria today in sub-Saharan Africa than any other time in
history. This region of the world bears the brunt of disease burden: a heavy
mortality toll that can reach up to 3 million lives especially among children
under the age of 5 and pregnant women, along with immense social and
economic costs that hamper people’s quality of life and perpetuate
underdevelopment. Because access to effective medicines or even to basic
tools are often lacking, a child dies from malaria every 30 seconds – over 2,500
young lives are lost every day.Error! Bookmark not defined.
According to the Centers for Disease Control, malaria is a serious, sometimes
fatal, disease caused by a parasite.4 Malaria is present in over 100 countries
and territories and more than 40% of the people in the world are at risk of
getting malaria.4
Symptoms of malaria include fever and flu-like illness, including shaking
chills, headache, muscle aches, and tiredness. Nausea, vomiting, and diarrhea
may also occur. Malaria may cause anemia and jaundice (yellow coloring of
the skin and eyes) because of the loss of red blood cells. Infection with one
8.1 CS1-3
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
type of malaria, Plasmodium falciparum, if not promptly treated, may cause
kidney failure, seizures, mental confusion, coma, and death.4
Malaria is diagnosed by looking for the parasites in a drop of blood. Blood
will be put onto a microscope slide and stained so that the parasites will be
visible under a microscope.4
Current Organizational Composition, Partners, and Funding:
Organization
MMV is composed of three teams: the Board of Directors; the Expert Scientific
Advisory Committee (ESAC), and the Management Team and Staff.5
The Board of Directors
According to its website, MMV is governed by a Board of a maximum of
twelve members, chosen for their scientific, medical and public health
expertise in malaria and related fields, their research and management
competence, as well as their experience in business, finance and fundraising.6
The MMV Board meets twice a year usually in Geneva at MMV headquarters.
It is the highest policy and decision-making body of the Foundation. Its main
duty is to ensure that the management, through the annual budget and work
plan, is efficiently executing the objectives of MMV. The Board establishes the
policies and principles followed by the Foundation and appoints the Chief
Executive Officer.
The board members are not compensated.3 Please refer to Annex 8.1.3, Section
A for a listing of MMV’s Directors.
The Expert Scientific Advisory Committee (ESAC)
The function of the Expert Scientific Advisory Committee (ESAC) is to advise
on the selection and review of projects for funding by MMV and to provide
more advice and general information on appropriate technical strategies for
the organization to achieve its goals.7
MMV’s ESAC is composed of voluntary members nominated by the CEO and
ratified by the Chair of the governing Board. Members are appointed for a
period of four years for up to two terms. Appointments are staggered to
provide a rotating membership.3 Please refer to Annex 8.1.3, Section A for a
list of ESAC members.
Management Team and Staff
8.1 CS1-4
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
The MMV team is responsible for all day-to-day operations of the
organization. The management team consists of the Chief Executive Officer, a
Chief Scientific Officer, a Chief Financial Officer and a Human Resources and
Administration Manager. A Director of International Operations, three
Scientific Officers, a Communications and Advocacy Officer and
administrative support staff, completes the team.3
The organization is very flat with the CEO managing MMV’s three strategic
areas of drug discovery & development, interfacing with drug supply
partners and supporting MMV through communications and fundraising.
The core drug discovery and development operations are managed by a Chief
Science Officer with a team of Scientific Officers and Science Team
Administrator. The International Operations Director supervises interface
activities. The Communications and Advocacy Officer and the CEO’s
Executive Assistant manage support activities.3
Please refer to Annex 8.1.3, Section A, for more information about MMV’s
Management Team.
Partners
MMV has partners who participate actively in the discovery and development
process as well as partners who provide funding for the organization.
To date, MMV has mobilized 33 partners in the drug discovery and
development process including research institutes, academic partners,
pharmaceutical companies, and international organizations.5
Funding
As of October 2003, MMV has succeeded in raising US $97 million from a
diverse set of public and philanthropic organizations.
MMV has received funding from: the Bill & Melinda Gates Foundation;
ExxonMobil Corporation; Global Forum for Health Research; International
Federation of Pharmaceutical Manufacturers Associations; Netherlands
Minister for Development Cooperation; Rockefeller Foundation; Swiss
Agency for Development and Cooperation; United Kingdom Department for
International Development; the World Bank; World Health Organization; Roll
Back Malaria; UNDP/World Bank/WHO Special Programme for Research and
Training in Tropical Diseases; and the Wellcome Trust.8
The Gates Foundation has pledged US $65 million to MMV. In 2000, the Gates
Foundation awarded US $25 million over five years and in 2003, pledged an
additional US $40 million over five years.9
8.1 CS1-5
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
8.1 CS1-6
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
The following figures represent the percentages of total contributions to MMV
from 1999 to October 2003:10
The Gates Foundation
UK DFID
Rockefeller Foundation
Netherlands Minister of Devt. Cooperation
WHO/Roll Back Malaria
Wellcome Trust
World Bank
Swiss Government
ExxonMobil Foundation
67%
11%
5%
5%
4%
3%
3%
2%
Less than 1%
No funds in support of this partnership have been received from the
European Union.
MMV has engaged in portfolio modeling to project future financial needs
which depending on the number of projects added and the rate at which the
projects proceed, planned expenditures over the next five years is estimated at
US $152 million including project and fixed costs. Total cost expenditures
exceed current funds by US $83 million.11
Strategy and Pipeline Overview
Strategy
In order to address the market failures that have produced a dearth of
research and development to support new malaria medicines, MMV has
chosen to address this problem through the vehicle of a public-private
partnership. Public-private partnerships are fast becoming the preferred way
to ensure that progress can be made in addressing those healthcare issues
which neither the public nor the private sector can solve on their own.12 The
combination of the pharmaceutical industry, with its knowledge and expertise
in drug discovery and development, and the public sector, with its depth of
expertise in basic biology, clinical medicine, field experience and above all its
public remit, constitutes the rationale for MMV.13
As stated above, MMV employs a three-component integrated strategy to
achieve its mission: drug discovery and development through portfolio and
project management; interfacing with global health actors to achieve health
impact; and conduct supporting activities including communications and
fundraising.3
According to MMV’s business plan, the core of MMV’s operations lies in
research and development enhanced by portfolio and project management.
8.1 CS1-7
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
Drug management is carried out in the laboratories of the academic and
pharmaceutical partner organizations funded by MMV. MMV’s Expert
Scientific Advisory Committee advises MMV’s management and scientific
team on the selection and termination of projects. Projects are co-managed by
MMV’s Scientific Officers with the academic and pharmaceutical partners.
MMV optimizes the likelihood and cost effectiveness of developing a new
antimalarial medicine based on its global perspective of research projects,
ongoing dialogues with scientists from both public and private sectors, and
the application of best practices in project and portfolio management.
The Business Plan further elaborates that “interface activities are a critical
complement to portfolio management. Through effective interfaces, MMV
leverages its public-private status to engage organizations to ensure that the
up and downstream drug supply prerequisites to health impact are achieved”.
The third strategic objective is focused on “supporting activities in
communications and fund raising” to ensure that the drug discovery and
development and the interface efforts are successful. Without adequate funds,
drug discovery and development projects cannot be completed and without
appropriate communication with the global actors in the field of public health,
the relevant partners will not be aware of MMV’s progress and the
implementation for health impact.3
Pipeline
As an organization dedicated to the discovery and development of
antimalarial medicines that are safe, effective, acceptable and affordable for
people living in endemic countries, MMV strives to have a balanced portfolio
that responds to these public health needs.
With a view to these priorities, target drug requirements include:3











Effectiveness against drug resistant strains of malaria (P. falciparum)
Treatment within three days to ensure patient compliance
Low propensity for drug resistance to emerge rapidly
Safe for small children (less than six months of age) and for
intermittent treatment in infancy
Safe for pregnant women and for intermittent treatment during
pregnancy
Appropriate formulations and packaging
Affordable to low income populations in endemic countries
Suitable for treatments in emergency situations (e.g. refugee camps)
Treatment against P. vivax
Treatment against severe malaria
Transmission blocking treatments
8.1 CS1-8
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
To date, MMV has 21 projects in various stages of discovery and development
with four additional backup projects selected. MMV believes the current
portfolio represents the largest single antimalarial drug research portfolio
since World War II and possibly ever.1 3 The portfolio includes new
compounds as well as improving existing compounds.
The following table sets out the various stages of drug discovery and
development as found on MMV’s website:
Table 8.1.7. MMV’s Approach to Drug Discovery and Development
Managing the stages of drug discovery and development
(from the MMV Annual Report 2002)
There is a high dropout rate in drug discovery and that may be due to a
number of factors including: a biologically poor target; lack of activity against
the target or parasite; toxicity; tolerability; or cost of goods.14
8.1 CS1-9
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
The following diagram show the 21 projects current undertaken by MMV.
Table 8.1.8. MMV’s Portfolio of Products and Stage of Development
MMV Portfolio
January 2004
Exploratory
Discovery
Lead
Lead
Identification Optimization
Glyceraldehyde
-3-phosphate
dehydrogenase
Fatty acid
biosynthesis
(Fab1)
Peptide
deformylase
inhibitor (PDF)
Dihydrofolate
reductase
(DHFR)
Falcipain
inhibitors
Fatty acid
biosynthesis
(FASII)
Protein
Farnesyl
Transferase
(Pf-PFT)
Preclinical
Transition
4(1H)Pyridones
Entantiomers
8-amino
quinolines
Phase I
Phase II
Phase III
Synthetic
peroxide
(OZ)
Manzamine
Alkaloids
New
dicationic
molecules
Clinical Development
Artemisone
(semi-synthetic
endoperoxide)
Isoquine
(superior 4aminoquinoline)
DHA
Piperaquine
Pyronaridine
artesunate
Intravenous
artesunate
ChlorproguanilDapsone
(LapDap™)
Artesunate
DB289
Pediatric
Coartem®
Novel
Tetracycline
Outlook and critical constraints
The portfolio of prospective candidates for an antimalarial medicine is
promising but several obstacles are facing MMV.
The major obstacle to the discovery of new antimalarial medicines is the lack
of global investment in drug R&D.15 The enormous costs and time needed for
R&D, with little or no prospect of return upon investment requires substantial
support from all sectors including government, international agencies, and
private industry. While MMV has raised US $97 million from November 1999
to November 2003, this number falls far short of even the most modest
financial projections.3
Fatty
acid
biosynthesis
(Fab1)
To date, the most funding received by MMV has come from the United States
while projected support from Europe and United Nations Organizations is
projected to decline.
8.1 CS1-10
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
Figure 8.1.4. MMV Funding by Geographical Area
MMV Funding Support Received/Pledged by Geographical Area
(December 2003)
18,000,000
16,000,000
US Dollars
14,000,000
12,000,000
10,000,000
8,000,000
6,000,000
4,000,000
2,000,000
0
2000
2001
2002
USA
2003
2004
EUROPE
2005
2006
2007
UN Organizations
MMV has taken steps to mitigate the high cost of drug discovery and
development. Through the partnership model, MMV avoids the need to
invest in infrastructure such as capital items. In-kind contributions by the
pharmaceutical industry and academic institutions are reducing the cost
through the donation or reduced pricing for compound libraries, technologies,
donated staff time, and infrastructure.3
Another obstacle is the high failure rate inherent in drug discovery and
development. MMV has taken steps to mitigate this concern through its
management practices which include: high profile in the scientific community
and among pharmaceutical partners; authoritative Expert Scientific Advisory
Committee; mission driven and fair project selection criteria; mission driven
and fair contractual conditions.3
8.1 CS1-11
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
Contact information:
Medicines for Malaria Venture (MMV)
International Center Cointrin
Block G, 3rd floor
20, route de Pré-Bois
PO Box 1826
1215 Geneva 15
Switzerland
Tel. +41(0) 22 799 4060
Fax +41 (0) 22 799 4061
www.mmv.org
email: info@mmv.org
References and key documents consulted:
Specific references are located at the end of the paper in the endnotes section.
Key documents and individuals consulted:
Hentschel C, Itoh M. The resurgence of Malaria and the role of the Medicines
for Malaria Venture, MMV publication available on the MMV website at:
www.mmv.org/filesUpld/105.pdf
Kettler H, Towse A, Public Private Partnership, CMH Working Paper Series,
Paper No. WG2:21.
MMV Annual Reports for 2002, 2001, and 2000
MMV Business Plan 2003-2007
Interviews conducted during the week of 1 March 2004 with Dr. Solomon
Nwaka, Scientific Officer, Mr. Peter Potter-Lesage, CFO, Dr. Lise Riopel,
Scientific Officer.
With special thanks to the members at MMV who contributed their time and
assistance to provide information for this case study.
8.1 CS1-12
Chapter 8.1 CS1: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
References to Case Study 1
Medicines for Malaria Ventures Annual Report 2002.
Website for Medicines for Malaria Venture, (www.mmv.org, accessed 4 March 2004).
3 MMV Business Plan 2003-2007.
4 The Centers for Disease Control and Prevention (CDC) is recognized as the leading United States
federal agency for protecting the health and safety of people - at home and abroad, providing credible
information to enhance health decisions, and promoting health through strong partnerships. CDC
serves as the United States national focus for developing and applying disease prevention and control,
environmental health, and health promotion and education activities designed to improve the health
of the people of the United States.
CDC, located in Atlanta, Georgia, USA, is an agency of the Department of Health and Human
Services.
(http://www.cdc.gov/travel/malinfo.htm, accessed 4 March 2004).
5 MMV Annual Report 2002.
http://www.mmv.org/pages/content_frame.asp?ThePage=page1_0002_1.htm&Nav=0002, accessed 4
March 2004).
6 MMV website, (www.mmv.org/pages/content_frame.asp?ThePage=page1_0002_1.htm&Nav=0002,
accessed 4 March 2004).
7 MMV website,
http://www.mmv.org/pages/content_frame.asp?ThePage=page1_0002_1.htm&Nav=0002, accessed 4
March 2004.
8 MMV Annual report 2002 MMV website at
http://www.mmv.org/pages/content_frame.asp?ThePage=page1_0002_1.htm&Nav=0002, accessed 4
March 2004.
9 Website for the Gates Foundation, grants section, (www.gatesfoundation.org, accessed 4 March
2004).
10 Information provided by Mr. Peter Potter-Lesage, Chief Financial Officer for MMV, in an interview
conducted 3 March 2004 at MMV, Geneva, Switzerland.
11 MMV Business Plan 2003-2007
12 MMV website, about MMV,
http://www.mmv.org/pages/content_frame.asp?ThePage=page1_0002_1.htm&Nav=0002, accessed 4
March 2004.
13 MMV website, about MMV,
http://www.mmv.org/pages/content_frame.asp?ThePage=page1_0002_1.htm&Nav=0002, accessed 4
March 2004.
14 MMV Website,
http://www.mmv.org/pages/content_frame.asp?ThePage=page1_0002_1.htm&Nav=0002, accessed 4
March 2004.
15 MMV Website,
http://www.mmv.org/pages/content_frame.asp?ThePage=page1_0002_1.htm&Nav=0002, accessed 4
March 2004.
1
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8.1 CS1-13