DEVELOPING NEW DRUGS & VACCINES FOR NEGLECTED DISEASES OF THE POOR - The Product Developer Landscape March 2012
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DEVELOPING NEW DRUGS & VACCINES
FOR NEGLECTED DISEASES
OF THE POOR
The Product Developer Landscape
March 2012
DEVELOPING NEW DRUGS & VACCINES FOR NEGLECTED DISEASES OF THE POOR The Product Developer Landscape Copyright © 2012 BIO Ventures for Global Health All rights reserved
This report was written by Elizabeth Ponder and Melinda Moree. Authors’ note: We acknowledge the Bill & Melinda Gates Foundation for its financial support. We would also like to acknowledge Molly Polen, Robert Schendle, Priya Mehta, and Don Joseph for their input and valuable feedback. This report is based on the BIO Ventures for Global Health Global Health Primer and associated database. The Global Health Primer is available online at www.globalhealthprimer.org.
C ONTENTS
Executive Summary ............................................................................................................3
Introduction .......................................................................................................................5
Results ...............................................................................................................................7
Overview of the Neglected Disease Research and Development (R&D) Pipeline ............7
Neglected Disease Pipeline by Disease ....................................................................8
Neglected Disease Pipeline by Product Type and Phase of Development...................8
Overview of Neglected Disease Product Developers.......................................................9
Partnering Among Neglected Disease Product Developers .......................................9
Neglected Disease Product Developers by Country ................................................10
Developer Participation by Organization Type ..............................................................11
Academic/Research Institutions ............................................................................12
Product Development Partnerships (PDPs) .............................................................16
Biotechnology Companies ....................................................................................20
Large Pharmaceutical Companies .........................................................................24
Other Developers .................................................................................................28
Comparison of Drug and Vaccine Pipelines ..................................................................28
Neglected Disease versus Overall R&D Activity by Country ...........................................31
Impact of Translational Research .................................................................................31
Product Development Outside of the Product Development Partnership (PDP) Model ...32
Comparison of Biotechnology and Pharmaceutical Company Participation ...................35
Discussion ........................................................................................................................40
Methodology....................................................................................................................43
Product and Disease Scope .........................................................................................43
Definitions .................................................................................................................44
Limitations .................................................................................................................45
FIGURE LIST
Figure 1. Overall Research and Development (R&D) Figure 22. Biotechnology Company Collaborations
Pipeline by Disease. ..........................................................................8 by Phase of Product Development...................................................22
Figure 2. Distribution of Drugs and Vaccines by Figure 23. Who is Partnering with Biotechnology
Phase of Development......................................................................8 Companies? ...................................................................................23
Figure 3. Unique Developers by Type Participating Figure 24. Large Pharmaceutical Company Pipeline
in Neglected Disease Product Development.......................................9 by Disease......................................................................................24
Figure 4. Unique Developers by Country or Region Figure 25. Large Pharmaceutical Company Participation
of Headquarters Participating in Neglected Disease in Drug Development by Phase .......................................................25
Product Development ......................................................................9
Figure 26. Large Pharmaceutical Company Participation
Figure 5. Unique Developers in Europe by Country in Vaccine Development by Phase ...................................................25
Participating in Neglected Disease Product Development .................10
Figure 27. Large Pharmaceutical Company Collaborations
Figure 6. Academic/Research Institution Pipeline by Number of Partners and Product Type .........................................26
by Disease......................................................................................12
Figure 28. Large Pharmaceutical Company Collaborations
Figure 7. Academic/Research Institution Participation by Phase of Product Development...................................................26
in Drug Development by Phase .......................................................13
Figure 29. Who is Partnering with Large Pharmaceutical
Figure 8. Academic/Research Institution Participation Companies? ...................................................................................27
in Vaccine Development by Phase ...................................................13
Figure 30. Country Neglected Disease R&D Activity
Figure 9. Academic/Research Institution Collaborations Relative to Overall R&D Activity ......................................................30
by Number of Partners and Product Type .........................................14
Figure 31. Neglected Disease Drug Pipeline with
Figure 10. Academic/Research Institution Collaboration No PDP Involvement by Phase ........................................................33
by Phase of Product Development...................................................14
Figure 32. Neglected Disease Vaccine Pipeline with
Figure 11. Who is Partnering with Academic/ No PDP Involvement by Phase ........................................................33
Research Institutions? ....................................................................15
Figure 33. Level of Participation of Other Developer
Figure 12. Product Development Partnership (PDP) Types in All Projects, Projects with PDP developers,
Pipeline by Disease .........................................................................16 and Projects with no PDP Developer................................................34
Figure 13. Product Development Partnership (PDP) Figure 34. Biotechnology and Pharmaceutical Company
Participation in Drug Development by Phase ...................................17 Participation in Drug Development by Phase ...................................37
Figure 14. Product Development Partnership (PDP) Figure 35. Biotechnology and Pharmaceutical Company
Participation in Vaccine Development by Phase ...............................17 Participation in Vaccine Development by Phase ...............................37
Figure 15. Product Development Partnership (PDP)
Collaborations by Number of Partners and Product Type ..................18
TABLE LIST
Figure 16. Product Development Partnership (PDP)
Collaboration by Phase of Product Development .............................18 Table 1. Diseases and Products Identified ..........................................7
Figure 17. Who is Partnering with Product Table 2. Level of Participation of Developers by
Development Partnerships (PDPs)?..................................................19 Organization Type for All Products, Drugs, and Vaccines ...................11
Figure 18. Biotechnology Company Pipeline by Disease ...................20 Table 3. Number of Products in Development per Company .............35
Figure 19. Biotechnology Company Participation in Table 4. Estimation of Pharmaceutical versus
Drug Development by Phase ...........................................................21 Biotechnology Contributions for Product Development ....................38
Figure 20. Biotechnology Company Participation in Table 5. Pharmaceutical Company Access to Medicines
Vaccine Development by Phase .......................................................21 Index R&D Scores and Number of Active Neglected
Disease Projects .............................................................................39
Figure 21. Biotechnology Company Collaborations
by Number of Partners and Product Type .........................................22 Table 6. Diseases and Products Included .........................................43
EXECUTIVE SUMMA RY
Understanding the research and development (R&D) pipeline disease R&D has focused to a large extent on the PDP
for neglected diseases as well as the spectrum of organizations model. However, our analysis found that more than half
participating in developing these new drugs and vaccines is of drug and vaccine development for neglected diseases is
essential to evaluate the efficiency and effectiveness of current occurring without a PDP partner.
R&D models and to inform the design of new programs and
• Industry participation in product development is simi-
initiatives to fill gaps in the neglected disease R&D pipeline.
lar for products with and without PDP development
However, this type of analysis has been hindered in part because
partners. The PDP model emphasizes promoting industry
neglected disease pipelines have not been systematically tracked.
partnership to accelerate product development. However,
Millions of lives could be saved through faster and more effi-
products with and without PDP participation have similar
cient R&D. It is critical to target our resources and R&D efforts
levels of partnership with both biotechnology and large
to provide the greatest benefit to the world’s poor.
pharmaceutical companies.
In 2011, BIO Ventures for Global Health (BVGH) released the
• Biotechnology company participation is higher than
new and expanded Global Health Primer, a report and online
anticipated with respect to the number of neglected dis-
database of compiled drug and vaccine development pipelines
ease products with at least one biotechnology company
for neglected diseases. Using this unique dataset, we explored
developer. Large pharmaceutical companies invest larger
for the first time the extent to which different types of organiza-
amounts of money in neglected disease R&D than small
tions are participating in drug and vaccine development for
companies; therefore, the high level of biotechnology com-
a broad range of neglected diseases. BVGH’s new analysis of
pany participation was surprising.
product developers participating in drug and vaccine develop-
ment revealed: • Biotechnology companies participating in neglected
disease R&D represent engagement of less than 3% of
• Academic/research institution participation is broad
the total number of biotechnology companies world-
and deep but often under recognized. Academic/
wide. Despite the large proportion of neglected disease
research institutions, better known for contributing to
pipeline products with biotechnology company participa-
our understanding of basic biology of neglected diseases,
tion, the 104 active companies identified represent a small
represent the highest number of unique developers, the
proportion of the more than 3,800 biotechnology compa-
greatest breadth of disease focus, the highest number of
nies worldwide. These data suggest biotech companies are
products with participation, and are involved in every
an underutilized resource for neglected disease R&D.
phase of development—for both drugs and vaccines—and
have partnered with every developer type profiled. • Large pharmaceutical companies participating in
neglected disease R&D represent engagement of
• The product development partnership (PDP) model
approximately 65% of the total number of large, innova-
for neglected disease R&D supports 40% of the overall
tor pharmaceutical companies. Although pharmaceuti-
neglected disease pipeline. Investment in neglected
cal companies are only participating in 17% of neglected
BIO Ventures for Global Health 3disease products in development, 13 of the 20 large, increasing the depth of participation of large pharmaceu-
innovator pharmaceutical companies are engaged. tical companies.
• The majority of pharmaceutical company participation • Translational research initiatives targeting academic/
is attributable to a minority of companies. Although research institutions should emphasize neglected disease
the 13 large pharmaceutical companies participating in product innovation.
neglected disease R&D participate in an average of 5.4
• Engagement of innovators from emerging market
products per company, 72% of products in development
countries still affected by neglected diseases should be
with a pharmaceutical company partner are being devel-
increased.
oped by just four companies.
This report serves as an in depth analysis of the organizations
• Neglected disease product developers primarily
developing products for neglected diseases and an overview
represent developed countries. Although the potential
of the neglected disease R&D pipeline (presented in more
for engagement of emerging market product developers
depth in the online BVGH Global Health Primer). The database
exists, our analysis suggests this potential has not yet
supporting this analysis will allow us to monitor trends and
been realized.
changes in both developer participation and product pipelines
Based on these findings, BVGH recommends that efforts to moving forward. In concert with data on U.S. Food & Drug
fill gaps in neglected disease pipelines be tailored to reflect the Administration (FDA) approvals and neglected disease R&D
needs, obstacles, and opportunities of each of the unique types funding, we hope our data will inform the evaluation of the effi-
of public and private organizations that comprise the global ciency and effectiveness of neglected disease R&D models. We
health product developers. Our analysis suggests that: believe the findings of this report are complementary to other
reports, and we hope the reported findings stimulate discussion
• New industry engagement should focus on engaging the
and action in the neglected disease R&D space.
full breadth of innovators in the biotechnology sector and
4 Developing New Drugs and Vaccines for Neglected Diseases of the PoorINTRODUCTION
Neglected diseases affect more than 1 billion people worldwide.1 Tuberculosis and Malaria—founded in 2002—brought billions
As the majority of those impacted are poor and living in devel- of dollars of financing to the improvement of health delivery
oping countries, commercial markets that traditionally drive systems and purchasing power to poor countries for lifesav-
pharmaceutical company investment in new product research ing drugs, vaccines, and diagnostics. In parallel, investment in
and development (R&D) are lacking. Investment in R&D for R&D for neglected diseases increased, largely focused on a new
new products to prevent or treat neglected diseases increased R&D funding vehicle now referred to as product development
substantially over the last two decades, primarily through public partnerships (PDPs).3 The PDPs were created to bring together
and philanthropic investment. However, a lack of systematic industry expertise and partners with complementary neglected
tracking of the organizations participating in product develop- disease expertise using philanthropic dollars in order to advance
ment and the products they support has made it difficult to product development. Total annual R&D funding for neglected
specifically target groups of product developers to fill gaps in diseases increased from $2.6 billion in 2007 to $3.1 billion in
the neglected disease R&D pipeline, evaluate the efficiency and 2010.4 PDPs are the largest recipients of neglected disease R&D
effectiveness of past investments, or inform the design of new funding. After the United States National Institutes of Health
programs and initiatives. (NIH), PDPs are the largest source of funding granted to others
for neglected disease R&D.5
Over the last two decades, the R&D landscape for new drugs
and vaccines that treat or prevent neglected diseases has Despite investment in neglected disease R&D, it has been
evolved. Overall development assistance in the health sector difficult to assess the impact of this investment on neglected
increased substantially during this timeframe, from $5.5 bil- disease product approvals and the size of neglected disease
lion in 1990 to $21.8 billion in 2007. The creation of entities
2
pipelines. Multiple factors contribute to the challenge, includ-
such as the Global Alliance for Vaccines and Immunization ing variations in definitions of neglected diseases, differences
(GAVI)—founded in 2000—and the Global Fund for AIDS, in how products in development are counted, and the lack of
1 World Health Organization (2012) “Accelerating Work to Overcome the Global Impact of Neglected Tropical Diseases: A Roadmap for
Implementation.”
2 Ravishanskar N et al. (2009) “Financing of global health: tracking development assistance for health from 1990 to 2007.” The Lancet 373: 2113-24;
Moran M (2005) “A Breakthrough in R&D for Neglected Diseases: New Ways to Get the Drugs We Need.” PLoS Medicine 2: e302; Moran M et al.
(2009) “Neglected Disease Research and Development: How Much Are We Really Spending?” PLoS Medicine 6: e1000030; Grace C (2010) Product
Development Partnerships (PDPS): Lessons from PDPDs established to develop new health technologies for neglected diseases, Department for
International Development, UK; Trouiller P et al. (2002) “Drug development for neglected diseases; a deficient market and a public-health policy
failure.” The Lancet 359: 2188-94.
3 Grace C (2010) Product Development Partnerships (PDPS): Lessons from PDPDs established to develop new health technologies for neglected
diseases, Department for International Development, UK; USAID (2009) Report to Congress: Coordinate Strategy to Accelerate Development of
Vaccines for Infectious Diseases, USA.
4 Moran M et al. (2011) Neglected Disease Research and Development: Is the Global Financial Crisis Changing R&D?, Policy Cures, Australia.
5 Moran M et al. (2011) Neglected Disease Research and Development: Is the Global Financial Crisis Changing R&D?, Policy Cures, Australia.
BIO Ventures for Global Health 5(BVGH) built and launched a new online
Global Health Primer database in 2011.9
Although BVGH produced snapshot
reports on subsets of the neglected dis-
ease pipeline in 2007 and 2009,10 the new
database facilitates tracking of changes in
the neglected disease product develop-
ment pipeline over time moving forward.
In this study, we used the Global Health
Primer dataset to identify 348 unique
organizations participating alone or
in partnerships with each other in the
development of 374 drugs and vaccines
for 23 neglected diseases. Each developer
was categorized by organization type to
explore trends in participation across
subsets of developers. We demonstrate
here that neglected disease product
development is being carried out by a
broad range of organization types and
participation varies greatly depending
on the product type, disease focus, and
systematic tracking of the neglected disease R&D pipelines over type of organization evaluated. Our findings suggest that, while
the last two decades. Between 1975 and 1999, estimates of new the PDP model for R&D and engaging large pharmaceuti-
product approvals for neglected diseases ranged from 16 to cal companies in product development has been a key focus
46. Counting methods varied between these studies and have
6
areas for global health, other less well recognized developer
been the subject of ongoing debate. Between 2000 and 2009,
7
types—including academic/research institutions and biotech-
26 additional products were approved, but debate over the nology companies—are making significant contributions to the
historical baseline number of U.S. Food & Drug Administration landscape. We hope these data will support the evolution and
(FDA) approvals has made it difficult to judge whether or not optimization of neglected disease R&D models in the future to
this number represents an increase. Unfortunately, compre-
8
better engage the full spectrum of neglected disease product
hensive data on the size of the pipelines that fed these approv- developers. While much progress has been made, much more
als are not available. In order to facilitate neglected disease work is still required to stop the suffering and death of the more
pipeline tracking over time, BIO Ventures for Global Health than 1 billion people affected by neglected diseases.
6 Trouiller P et al. (2002) “Drug development for neglected diseases; a deficient market and a public-health policy failure.” The Lancet 359: 2188-94;
Cohen J et al. (2010) “Development of and Access to Products for Neglected Diseases.” PLoS ONE 5: e10610.
7 Commentary on the Cohen 2010 paper and the author’s rebuttle is available on the PLoS ONE website; Adams P (2011) “The ongoing debate over
R&D output.” TropIKA.net.
8 Cohen J et al. (2010) “Development of and Access to Products for Neglected Diseases.” PLoS ONE 5: e10610.
9 BVGH Global Health Primer, available at: http://www.bvgh.org/Biopharmaceutical-Solutions/Global-Health-Primer.aspx
10 BVGH (2007) Global Health Primer. BVGH (2009) Global Health Primer.
6 The Product Developer LandscapeR ESULTS
OVERVIEW OF THE NEGLECTED DISEASE
RESEARCH & DEVELOPMENT (R&D)
health community. For the purposes of this study, 23 diseases
PIPELINE
were included, falling into three broad categories as described in
In order to investigate which organizations are participating in the methods section. The full list of diseases and whether drugs
product development for neglected diseases, it was necessary and/or vaccines were identified for each disease are listed in
to first identify all of the products in development for neglected Table 1.
diseases. Neglected diseases are categorized as a single group
More information on how diseases and products were identified
due to neglect rather than their biological or medical basis.
and categorized can be found in the methods section along with
Therefore, the term “neglected” has been difficult to define and
a table detailing which product types were included for evalua-
challenging to gain consensus around, even within the global
tion for each disease (Table 6).
Table 1. Diseases and Products Identified
DISEASE DRUGS VACCINES
BIG THREE
HIV 9 (Microbicides) 48
Tuberculosis 49 45
Malaria 44 23
OTHER NEGLECTED TROPICAL DISEASES
Buruli ulcer 2 2
Chagas disease 9 0
Dengue 11 13
Fascioliasis 4 1
HAT 10 1
Leprosy N/A 1
Leishmaniasis 20 7
Lymphatic filariasis 2 2
Onchocerciasis 3 2
Schistosomiasis 4 5
STH: Hookworm 0 2
STH: Ascariasis & Trichuriasis 1 0
Trachoma N/A 4
OTHER IMPORTANT DISEASES OF POVERTY
Diarrheal disease 4 N/A
Cholera N/A 5
ETEC N/A 11
Rotavirus N/A 4
Shigellosis N/A 7
Typhoid fever N/A 6
Pneumococcal disease N/A 13
The neglected diseases included in this study are summarized here. Diseases are divided into three general categories. The numbers of products identified
are listed. Those product types not researched for inclusion are designated by not applicable (N/A); STH=Soil Transmitted Helminths
BIO Ventures for Global Health 7Neglected Disease Pipeline by Disease Neglected Disease Pipeline by Product Type
and Phase of Development
Using the criteria described above and outlined in more detail
in the methods section, 374 drugs and vaccines currently in Of the 374 products identified, 173 products were drugs (46%
development were identified for 23 neglected diseases that dis- of all products) and 201 products were vaccines (54% of all
proportionately affect the developing world. Figure 1 summa- products) (Figure 2). The distribution of drugs and vaccines
rizes the distribution of these products across the 23 diseases. across the phases of development differ by product type.
The drug development pipeline is shaped much as would be
As expected, drugs (including microbicides) and vaccines for
expected and desired, given the likelihood of attrition across the
malaria, tuberculosis, and HIV (the “big three”) represent the
development phases, with the majority of products in the early
largest proportion of the pipeline, totaling 218 out of 374 total
stages and tapering off at the later stages of clinical develop-
products (58%; Figure 1). Fewer products are in development
ment. In contrast, there are relatively even numbers of vaccines
for other neglected diseases, such as those characterized as
in pre-clinical through phase II clinical development, dropping
“neglected tropical diseases” by the World Health Organization,
off only at phase III. Differences in the vaccine and drug pipe-
and diarrhea and pneumonia, which are often excluded from
lines will be discussed in more detail in subsequent sections.
neglected disease analyses but have a significant disproportion-
ate effect on the world’s poor.
Figure 1 Overall Research and Development (R&D) Figure 2 Distribution of Drugs and Vaccines by Phase
Pipeline by Disease of Development
218 106 50 80
STH: Ascariasis & Trichuriasis 1
Leprosy 1
STH: Hookworm 2
Diarrheal Disease
Buruli Ulcer 4 4
75
Lymphatic filariasis 4 Rotavirus
HIV 70 Drug
Trachoma 4 4
57
Fascioliasis 5
Vaccine
Cholera
Onchocerciasis 5 Cholera
5
60
Chagas Disease
9
Typhoid Fever
Schistosomiasis 6
56
Tuberculosis 54
9
67 50
50
Number of Products
HAT Shigellosis
11 7 47
40
Dengue 35
24 ETEC
11 30
Malaria
94
20
Leishmaniasis
Pneumococcal Disease 18
13 16
27 14
10
9
The "Big Three" Other Neglected Other Important
Tropical Diseases Diseases of Poverty 0
Discovery Pre-Clinical Phase I Phase II Phase III
The disease name and total number of products covered in this study are
summarized in the Mekko plot here. The area of each rectangle in the Mekko
plot is proportional to the number of products for that disease. Restrictions on The total number of drugs (including HIV microbicides) and vaccines were summed
drugs or vaccines evaluated for each disease are summarized in Table 6. The total for each phase of development.
number of products in each of the three disease categories is listed at the top
of the column.
8 Developing New Drugs and Vaccines for Neglected Diseases of the PoorOVERVIEW OF NEGLECTED DISEASE
PRODUCT DEVELOPERS
rarely occurs within a single organization. Therefore, we
The 374 drugs and vaccines included in this study are in
determined how many developers were associated with each
development by 348 organizations spanning both the private
neglected disease product identified in this study by calculating
and public sectors as summarized in Figure 3. Definitions of
the average number of unique developers associated with each
organization types used to categorize developers are provided
product. Of the 374 products in development, 39% were found
in the methods section and will be discussed in more detail in
to be in development by a single organization with no partners
subsequent sections. Academic/research institutions and bio-
(data not shown). The average number of developers was 2.2
technology companies represent the largest number of unique
unique developers per product. The average number of partners
organizations (Figure 3).
varied little for drugs as compared to vaccines (2.1–2.3) or phase
Partnering Among Neglected Disease Product of development (1.9–2.7) (data not shown). These averages only
Developers reflect the number of partners associated with products in this
study at the time of analysis and do not account for developers
While 348 unique organizations were identified, it is generally
who may have participated in development at earlier stages but
understood that product development for neglected diseases
are no longer involved.
Figure 3 Unique Developers by Type Participating in Figure 4 Unique Developers by Country or Region of
Neglected Disease Product Development Headquarters Participating in Neglected Disease
Product Development
Other Non-profit South Africa Other Africa
Other Industry Academic/Research 4 (1%)
7 (2%) 8 (2%)
Institution Other Asia
25 United States
Big Pharma 136 China 17
13 (7%) 11
(4%) (39%) (5%)
India (3%) 129
PDP Japan 18
26 (37%)
7 (2%) (5%)
(7%)
Government Australia/ 16
New Zealand (5%)
37
(11%) Russia
3 (1%)
115
104 Europe (33%) 14
(30%) (4%)
Brazil
Other 6 (2%)
Biotech Americas
Organizations identified as participating in the development of the 374 products Organizations identified as participating in the development of the 374 products
included in this study were categorized by organization type. Here, the proportion included in this study were categorized by country or region of headquarters. Here,
of the total 348 unique organizations identified is presented by organization type. the proportion of the total 348 unique developers identified is presented by coun-
try or region.
BIO Ventures for Global Health 9Neglected Disease Product Developers
by Country
Neglected diseases disproportionately affect the developing
world, but drug and vaccine research and development outside
of neglected diseases traditionally occur in the developed world.
Therefore, the country or region of each of the 348 unique
developer’s headquarters was evaluated as a surrogate mea- Figure 5 Unique Developers in Europe by Country
surement of the participation of developed versus developing Participating in Neglected Disease Product
Development
country organizations in product development. The number of
unique organizations participating in product development for Europe (not specified) 1 (1%)
neglected diseases is summarized by country of headquarters Hungary 1 (1%)
Austria
in Figure 4. European organizations participating in neglected 1 (1%) Iceland 1 (1%)
Portugal 1 (1%)
Ireland 3 (3%)
disease drug development are further broken down by country United Kingdom Norway 3 (3%)
Spain 4 (3%)
in Figure 5.
Belgium
The majority of developers participating in neglected disease 27
(23%) 5 (4%)
product development were based in the United States, Europe, Denmark
5 (4%)
and other developed countries (246 out of 348 unique develop-
ers, or 71% of all developers identified; Figure 4). While there 5 (4%) Italy
were some developers from Brazil, India, China, Russia, and 5 (4%)
15 Sweden
South Africa—known to be innovative, emerging market coun- (13%)
tries, these made up a small minority of organizations identified Netherlands 12
13 (10%)
in this study. (11%)
13 France
(11%)
European country governments and the European Commission
account for nine of the top 12 public sector funders of neglected Switzerland
Germany
disease R&D. 11
Therefore, we looked at the distribution of
developers across European countries in more detail (Figure 5). Organizations identified as participating in the development of products for
neglected diseases headquartered in Europe were counted based on country of
The United Kingdom had the largest number of developers par- headquarters. Here, the proportion of the total 115 unique developers identified
ticipating in neglected disease product development followed as being headquartered in Europe are presented by country.
by the Netherlands, Switzerland, Germany, and France.
11 Moran M et al. (2011) Neglected Disease Research and Development: Is the Global Financial Crisis Changing R&D?, Policy Cures, Australia
10 The Product Developer LandscapeDEVELOPER PARTICIPATION BY
ORGANIZATION TYPE
in neglected disease product development, such as the extent
For the purposes of this report, we chose to focus on four
to which each organization contributes money, employee time,
developer categories: academic/research institutions, product
physical reagents, know-how, etc. This is particularly true in the
development partnerships (PDPs), biotechnology companies,
case of products with multiple development partners. Here, and
and large pharmaceutical companies. Table 2 provides an
for the remainder of this analysis, all participation in product
overview of the level of participation of each organization type
development in the context of a partnership is assumed equal.
as measured by the percentage of products in development with
While this is an oversimplification, it provides a mechanism to
at least one associated developer of that type.
understand the level of participation of different organization
When we calculated how many products in development had at types in terms of number of products as a proportion of all
least one academic/research institution, PDP, or biotechnology products in development.
company participating in development, similar proportions of
products in development for neglected
diseases were identified for each organiza-
tion type, whether analyzed in the aggre-
gate (40–43%) or segregated by drugs and
vaccines (39–40% for drugs and 39–46%
for vaccines) (Table 2). Using this same
approach, large pharmaceutical companies
were participating in 17% of products in
development with lower participation in
vaccines as compared to drugs (10% versus
32%, respectively). The participation of
each organization type in neglected disease
product development is examined in more
detail in the subsequent sections.
The current analysis is not designed to
quantify or provide qualitative assessment
of the nature of developer participation
Table 2. Level of Participation of Developers by Organization
PRODUCTS WITH AT LEAST ONE DEVELOPER OF THIS TYPE
TOTAL PRODUCTS DRUGS VACCINES
DEVELOPER TYPE
(% OF ALL PRODUCTS) (% OF ALL DRUGS) (% OF ALL VACCINES)
Academic/Research Institution 162 (43%) 69 (40%) 93 (46%)
PDP 149 (40%) 70 (41%) 79 (39%)
Biotech 153 (41%) 68 (39%) 85 (42%)
Big Pharma 65 (17%) 44 (25%) 21 (10%)
*Note: the percentages will not total to 100% as several developers may be involved with the R&D of a unique drug or vaccine.
BIO Ventures for Global Health 11Academic/Research Institutions
Academic/Research institutions made up the largest number
of organizations participating in neglected disease product
development (129 out of 348 total unique organizations; Figure
3). They participated in the development of the greatest number
of products (162 of 374 products, 43%; Table 2) and the great-
est range of diseases with products in development (20 of the
23 neglected diseases included in this study; Figure 6) of any
individual developer type. Figure 6 Academic/Research Institution Pipeline by
Disease
Academic/research institutions are participating in the devel-
88 52 18
opment of a greater number of vaccines than drugs (Figure 7 STH: Ascariasis & Trichuriasis 1
Shigellosis 1
and Figure 8), but their participation across drugs, vaccines, Lymphatic filariasis 3
and phases of development was largely reflective of the overall HIV Trachoma 3 Rotavirus
2
20
pipeline (Figure 2) and relatively consistent across drugs, vac- Onchocerciasis 3
cines, and phases of development, ranging from participation Buruli Ulcer
Cholera
2
4
in 21-54% of products in a given phase (Figure 7 and Figure Fascioliasis
4
Typhoid Fever
8). In general, academic/research institutions are participating 2
Tuberculosis
in more discovery and preclinical phase products with lesser 20 Chagas Disease
6
participation as product development moves into the clinical
phases of testing (Figure 7 and Figure 8). Schistosomiasis Pneumococcal Disease
5
7
As most products in development for neglected diseases are
being developed by partnerships of multiple organizations, we HAT
8
next wanted to assess the extent to which academic/research Malaria
48
institutions partner with other organizations. While we could
not assess the nature of partnerships using the current dataset, ETEC
6
Leishmaniasis
we could determine the average number of partners participat- 13
ing in the development of drugs or vaccines with at least one
academic/research institution developer. The number and
proportion of all products with at least one academic/research The "Big Three" Other Neglected Other Important
Tropical Diseases Diseases of Poverty
institution developer with zero, one, two, or three/greater than
three partners is summarized in Figure 9 by product type and The disease name and total number of products with at least one academic/
research institution developer covered in this study are summarized in the Mekko
Figure 10 by phase of development.
plot here. The area of each rectangle in the Mekko plot is proportional to the
number of products for that disease. Restrictions on drugs and vaccines evaluated
On average, products in development for neglected diseases for each disease are summarized in Table 6. The total number of products in each
with at least one academic/research institution developer have of the three disease categories is listed at the top of the column.
more partners per product than the neglected disease pipeline
12 Developing New Drugs and Vaccines for Neglected Diseases of the Pooras a whole—2.9 total developers per product as compared to The number of partners associated with products in develop-
2.2 for the composite pipeline (Figure 9; Figure 10). Also, the ment with at least one academic/research institution developer
number of products in development with an academic/research raised the question as to what types of organizations academic/
institution developer with no additional partners was 19% research institutions are collaborating or partnering with. For
(30 total products; Figure 9) which is less than the 39% of the each of the 132 products in development that have at least one
neglected disease pipeline as a whole (146 total products). While academic/research institutions and at least one additional part-
there is essentially no difference in the average number or distri- ner, we asked what organization types any additional partners
bution of developer numbers by drug or vaccine (Figure 9), the represented. For example, if a product in development by an
number of partners per product is higher for products in late academic/research institution was also partnered with a PDP
stage clinical development than early stage products (Figure 10). and a pharmaceutical company, that product is counted as a col-
laboration between an academic research institution and a PDP
F i gure 7 Academic/Research Institution Participation Figure 8 Academic/Research Institu tion Participation
in Drug Development by Phase in Vaccine Development by Pha se
DRUGS IN DEVELOPMENT VACCINES IN DEVELOPMENT
40 60% 40 60%
54%
54%
35 36
48% 50% 50%
30 30
30 40%
Percentage of All Vaccines
38% 40% 41% 40%
Percentage of All Drugs
25 40%
Number of Products
Number of Products
20 22 33%
20 30% 30%
20 19 19
15
22% 21% 20% 20%
10 10
10% 10%
5 6
4 3
3 0
0 0% 0%
Discovery Pre-Clinical Phase I Phase II Phase III Discovery Pre-Clinical Phase I Phase II Phase III
The total number of drugs with at least one academic/research institution devel-
oper was summed for each phase of development in the bar graph (left Y-axis). The total number of vaccines with at least one academic/research institution
The percentage of drugs in the given phase of development with at least one developer was summed for each phase of development in the bar graph (left
academic developer relative to the total number of drugs at the indicated phase Y-axis). The percentage of vaccines in the given phase of development with at
was calculated and presented as a line (right Y-axis). least one academic developer relative to the total number of vaccines at the indi-
cated phase was calculated and presented as a line (right Y-axis).
BIO Ventures for Global Health 13F i gure 9 Academic/Research Institution Figure 10 Academic/Research Institu tion
Co llaborations by Number of Partners and Collaboration by Phase of Product
Product Type Development
Total # of Products Total # of Products
162 69 93 162 55 50 28 23 6
100% 100%
21% 15% 12% 11% 57% 67%
34 (21%) 14 (20%) 20 (22%)
80% 24 (35%) 80%
29% 40% 32% 21%
47 (29%) 23 (25%)
21 (30%)
60% 60%
51 (31%)
30 (32%)
4%
40% 40%
31% 29% 26% 61% 22%
30 (19%) 10 (14%) 20 (22%) 20% 33%
20%
19% 16% 30% 7% 17%
0% All Dru Vac 0% All Dis Pre Pha Pha Pha
Pro Pro c -Cli
duc gs c ine
s duc overy nic
se
I
se
II se
III
ts ts al
2.9 2.8 2.9 2.9 2.9 2.5 2.6 3.2 5.8
Average # of Partners 3+ Partners
Average # of Partners 3+ Partners
2 Partners
2 Partners
1 Partner
1 Partner
No Partners
No Partners
For all products with at least one academic/research institution developer, the
For all products with at least one academic/research institution developer, the number of additional developers associated with that product was counted. Each
number of additional developers associated with that product was counted. Each bar graph segment is number of products with the given number of partners for
bar graph segment is number of products with the given number of partners for all products for each phase of development and the proportion of all products
all products, drugs, or vaccines and the proportion of all products (%) with that (%) with that number of partners. The total at the top of the column is the total
number of partners. The total at the top of the column is the total number of prod- number of products with at least one academic/research institution partner at the
ucts with at least one academic/research institution partner. The average number given phase. The average number of partners per product at each phase with at
of partners per product across all products, drugs, or vaccines with at least one least one academic/research institution partner is given below the graph.
academic/research institution partner is given below the graph.
2.9 2.9 2.5 2.6 3.2 5.8
14 The Product Developer Landscape(one of the 47 products counted in the bar labeled “PDP”) and a development, including other academic/research institutions,
collaboration between and academic/research institution and a PDPs, biotechnology companies, large pharmaceutical compa-
pharmaceutical company (one of 18 products counted in the bar nies, and other organization types not included in this analy-
labeled “Big Pharma”) in Figure 11. The results of this analysis sis. At least half of all projects had at least one PDP partner,
are presented in Figure 11. irrespective of product type (Figure 11). This was not surprising
as partnerships are necessary to drive early stage discoveries in
Academic/research institutions participated in collaborations
academia toward product development.
with all other organization types for neglected disease product
Fi gure 11 Who is Partnering with Acad emi c/Research Institutions?
35 (23%)
Total Projects
79 (53%)
47 (32%)
18 (12%)
50 (34%)
23 (33%)
Other Academic
38 (54%)
Drug Projects
PDP
17 (24%) Biotech
13 (19%)
Big Pharma
13 (19%)
Other
12 (15%)
Vaccine Projects
41 (52%)
30 (38%)
5 (6%)
37 (47%)
0 10 20 30 40 50 60 70 80
# of Products (% of All Products)
For each of the 132 products in development that have at least one academic/research institution developer and at least one additional partner, it was determined whether
the additional partner(s) included at least one of the following developer types: other academic/research institution, PDP, biotechnology company, large pharmaceutical
company, or some other type of organization. The number of products and the proportion of all products, drugs, or vaccines with an academic/research institution developer
and at least one of the indicated organization types as a partner are given at the end of each bar.
BIO Ventures for Global Health 15Product Development Partnerships (PDPs)
Although there are a relatively small number of PDPs (26
unique organizations identified in this study), 40% of products
in development have at least one PDP developer (149 products;
Table 2). Given the emphasis on the PDP model for new fund-
ing for neglected disease research and development (R&D) in
the last 10 years,12 it is interesting to note that more than half of
the products identified here are being developed outside of this
R&D model. Figure 12 Product Development Partn ership (PDP)
Pipeline by Disease
PDPs have products in development for 16 of the 23 diseases 91 33 24
included in this study (Figure 12). Well over half (61%) of the Buruli Ulcer 1 Typhoid Fever 1
Leprosy 1
Cholera 2
products with PDP participation are in development for HIV Schistosomiasis 1
HIV
(microbicides and vaccines only), malaria, and tuberculosis. 22 Chagas Disease Diarrheal Disease 2
5
PDPs are participating in the development of a greater number Shigellosis
2
of vaccines than drugs (Figure 13 and Figure 14), and their par-
ticipation across drugs, vaccines, and phases of development is Tuberculosis HAT Rotavirus
9 4
largely reflective of the overall pipeline (Figure 2) and relatively 26
consistent across drugs, vaccines, and phases of development,
ranging from participation in 22-57% of products in a given
ETEC
phase (Figure 13 and Figure 14). 5
Surprisingly, PDPs are only involved in 10 of the 23 total prod-
ucts in phase III, representing participation in 43% of products Malaria Leishmaniasis
43 16
at this phase (Figure 13 and Figure 14). If we break participa- Pneumococcal
Disease
tion in phase III products down by products type, PDPs are 8
participating in 57% of drugs in phase III development (Figure
13) but only 22% of vaccines in phase III development (Figure
14). Because of the expense of phase III clinical trials and the
The "Big Three" Other Neglected Other Important
emphasis on public-private sharing of financial risk fostered by Tropical Diseases Diseases of Poverty
the PDP model, we would have expected nearly all the phase III
The disease name and total number of products with at least one PDP developer
trials to involve a PDP.
covered in this study are summarized in the Mekko plot here. The area of each
rectangle in the Mekko plot is proportional to the number of products for that dis-
As the PDP model is designed for foster partnership, particu- ease. Restrictions on drugs or vaccines evaluated for each disease are summarized
larly between the public and private sectors, we next wanted in Table 1. The total number of products in each of the three disease categories is
listed at the top of the column.
to assess the extent to which PDPs partnered with other
organizations on the products identified in this study. While
we could not assess the nature of these partnerships, we could
determine the average number of partners participating in the
12 Grace C (2010) Product Development Partnerships (PDPS): Lessons from PDPDs established to develop new health technologies for neglected
diseases, Department for International Development, UK; USAID (2009 Report to Congress: Coordinate Strategy to Accelerate Development of
Vaccines for Infectious Diseases, USA.
16 Developing New Drugs and Vaccines for Neglected Diseases of the Poordevelopment of drugs or vaccines with at least one PDP devel- 15) as compared to 39% of the neglected disease pipeline as a
oper. The number and proportion of all products with at least whole. There is little variation in the number of collaborators
one PDP developer with zero, one, two, or three/greater than participating in products with at least one PDP developer by
three partners is summarized in Figure 15 by product type and drugs, vaccines, or by phase, although the average number of
Figure 16 by phase of development. partners increases slightly in the late clinical stages of develop-
ment (Figure 16).
On average, products in development for neglected diseases
with at least one PDP developer have more partners per product PDPs, both by design and in the data presented here, use part-
than the neglected disease pipeline as a whole—3.1 total devel- nering as part of their core model for neglected disease R&D.
opers per product as compared to 2.2 for the composite pipeline Therefore, for those products with at least one PDP developer,
(Figure 15; Figure 16). Also, PDPs have virtually no products in we asked which types of organizations PDPs were collaborating
development with no additional development partners (Figure with. For each of the 142 products in development that have
Fi gure 13 Pro duct Development Partnershi p (PDP) Figure 14 Product Development Partnership (PDP)
Participation in Drug Development by Phase Participation in Vaccine Development by
Phase
DRUGS IN DEVELOPMENT VACCINES IN DEVELOPMENT
40 57% 60% 40 60%
35 50% 47% 50%
47%
30 30 43%
44% 41%
Percentage of All Vaccines
40% 40%
Percentage of All Drugs
38%
Number of Products
Number of Products
20 20 26% 22 22
30% 30%
26% 18
20% 15 22% 20%
13
10 10
8 8 10% 10%
6
0 2
0% 0 0%
Discovery Pre-Clinical Phase I Phase II Phase III Discovery Pre-Clinical Phase I Phase II Phase III
The total number of drugs with at least one PDP developer was summed for each The total number of vaccines with at least one PDP developer was summed for
phase of development in the bar graph (left Y-axis). The percentage of drugs in the each phase of development in the bar graph (left Y-axis). The percentage of vac-
given phase of development with at least one PDP relative to the total number of cines in the given phase of development with at least one PDP relative to the total
drugs at the indicated phase was calculated and presented as a line (right Y-axis). number of vaccines at the indicated phase was calculated and presented as a line
(right Y-axis).
BIO Ventures for Global Health 17F i gure 15 P ro duct Development Partnershi p (PDP) Figure 16 Product Development Partnership (PDP)
Collaborations by Number of Partners and Collaborations by Phase of Product
Pro duct Type Development
Total # of Products Total # of Products
149 70 79 124 45 28 24 23 8
100%
100% 15% 11% 11% 13% 30% 13%
40 (27%) 17 (24%) 23 (29%)
43% 47% 57% 38% 13%
80%
80%
26%
60% 60%
53 (36%) 27 (39%) 26 (33%)
40% 40%
40% 40% 18% 50% 35% 75%
49 (33%) 23 (33%) 26 (33%)
20% 20%
14% 9%
7 (5%) 3 (4%) 4 (5%) 2% 2%
0% All Dru Vac 0% All Dis Pre Pha Pha Pha
Pro c -Cli
Pro
duc gs c ine duc overy nical
se
I
se
II se
III
ts s ts
3.1 3.0 3.1 3.1 3.0 3.0 3.1 3.3 3.4
Average # of Partners 3+ Partners Average # of Partners 3+ Partners
2 Partners 2 Partners
1 Partner 1 Partner
No Partners No Partners
For all products with at least one PDP developer, the number of additional devel- For all products with at least one PDP developer, the number of additional devel-
opers associated with that product was counted. Each bar graph segment is opers associated with that product was counted. Each bar graph segment is num-
number of products with the given number of partners for all products, drugs, or ber of products with the given number of partners for all products for each phase of
vaccines and the proportion of all products (%) with that number of partners. The development and the proportion of all products (%) with that number of partners.
total at the top of the column is the total number of products with at least one PDP The total at the top of the column is the total number of products with at least one
partner. The average number of developers per product across all products, drugs, PDP partner at the given phase. The average number of developers per product at
or vaccines with at least one PDP partner is given below the graph. each phase with at least one PDP partner is given below the graph.
18 The Product Developer Landscapeat least one PDP and at least one additional partner, we deter- academic/research institutions for both drugs and vaccines.
mined what organization types any additional partners repre- Collaboration with biotechnology and pharmaceutical compa-
sented. The results are presented in Figure 17. nies differed for drugs as compared to vaccines. Biotechnology
companies were collaborating with PDPs on 46% of PDP vac-
PDPs partnered with the full range of organization types exam-
cine projects but only 21% of PDP drug products (Figure 17).
ined in this study, including other PDPs, academic/research
In contrast, pharmaceutical companies were collaborating with
institutions, biotechnology companies, pharmaceutical compa-
PDPs on 36% of PDP drug projects and only 6% of PDP vaccine
nies, and others. PDPs collaborated to the greatest extent with
projects (Figure 17).
Fi gure 17 Who is Partnering with Product Development Partnerships (PDPs)?
79 (53%)
Total Projects
23 (15%)
51 (34%)
30 (20%)
56 (38%)
38 (54%)
Academic/Research Institution
10 (14%) Other PDP
Drug Projects
15 (21%) Biotech
25 (36%)
Big Pharma
19 (27%)
Other
41 (52%)
Vaccine Projects
13 (16%)
36 (46%)
5 (6%)
37 (47%)
0 10 20 30 40 50 60 70 80
# of Products (% of All Products)
For each of the 142 products in development that have at least one PDP developer and at least one additional partner, it was determined whether the additional partner(s)
included at least one of the following developer types: other PDP, academic/research institution, biotechnology company, large pharmaceutical company, or some other type
of organization. The number of products and the proportion of all products, drugs, or vaccines with a PDP developer and at least one of the indicated organization types as
a partner.
BIO Ventures for Global Health 19Biotechnology Companies
Biotechnology companies make up the second largest number
of organizations participating in neglected disease product
development (104 out of 348 total unique organizations; Figure
3). These companies participated in the development of 153 of
374 products (41%; Table 2) and 16 of the 23 neglected dis-
eases included in this study (Figure 18). Unlike the academic/
research institutions and PDPs already profiled, the neglected
tropical disease with the largest number of products in devel- Figure 18 Biotechnology Company Pipeline by Disease
opment with at least one biotechnology company partner was
90 35 28
dengue, with 16 products (Figure 18). Buruli Ulcer 1
Rotavirus
Lymphatic filariasis 1
2
Biotechnology companies participated in the development HIV Schistosomiasis 1
14 HAT Shigellosis
of a greater number of vaccines than drugs and their pattern 3 3
of participation varies greatly by product type (Figure 19 and
Figure 20). Diarrheal Disease
4
Participation in drug development was greatest in the discovery Tuberculosis
Leishmaniasis
13
and pre-clinical phases with 29 and 30 products, represent- 33 Typhoid Fever
4
ing participation in 39 and 60% of all drugs at those phases
(Figure 19), respectively. In the pre-clinical stage in particular,
Cholera
biotechnology company participation was higher than any 5
other developer type (Figure 19). The high level of participation
in pre-clinical stage projects is interesting, as this is generally Dengue
Malaria
16
considered the “valley of death” in neglected disease product 43 ETEC
5
development. Biotechnology company participation is sub-
stantially lower for products in the later clinical stages of drug
Pneumococcal
development (Figure 19). Disease
5
In contrast, biotechnology company participation in vaccine
The "Big Three" Other Neglected Other Important
development is high across products in discovery through Tropical Diseases Diseases of Poverty
phase II of development, ranging from participation in 39-51%
of all vaccines at these phases of development (Figure 19 and The disease name and total number of products with at least one bio-
tech developer covered in this study are summarized in the Mekko plot
Figure 20). The high level of biotechnology company participa-
here. The area of each rectangle in the Mekko plot is proportional to the
tion through phase II is surprising as phase II efficacy trials number of products for that disease. Restrictions on drugs and vacciens
are expensive. evaluated for each disease are summarized in Table 1. The total number
of products in each of the three disease categories is listed at the top of
As biotechnology company participation differed substantially the column.
across drugs, vaccines, and phases of development, we wanted
to understand if the extent of collaborations of biotechnology
companies differed across these parameters. While we could not
assess the nature of these partnerships, we could determine the
20 Developing New Drugs and Vaccines for Neglected Diseases of the PoorYou can also read
