DEVELOPING NEW DRUGS & VACCINES FOR NEGLECTED DISEASES OF THE POOR

 
 
DEVELOPING NEW DRUGS & VACCINES FOR NEGLECTED DISEASES OF THE POOR
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
DEVELOPING NEW DRUGS & VACCINES
FOR NEGLECTED DISEASES OF THE POOR
The Product Developer Landscape




Copyright © 2012 BIO Ventures for Global Health
All rights reserved
DEVELOPING NEW DRUGS & VACCINES FOR NEGLECTED DISEASES OF THE POOR
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.
DEVELOPING NEW DRUGS & VACCINES FOR NEGLECTED DISEASES OF THE POOR
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
DEVELOPING NEW DRUGS & VACCINES FOR NEGLECTED DISEASES OF THE POOR
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
DEVELOPING NEW DRUGS & VACCINES FOR NEGLECTED DISEASES OF THE POOR
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                                                                                                     3
disease 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 Poor
INTRODUCTION

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 Landscape
R 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                                                                                                                               7
Neglected 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 Poor
OVERVIEW 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                                                                                                                                              9
Neglected 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 Landscape
DEVELOPER 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                                                                                                                           11
Academic/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 Poor
as 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                                                                                                                                                                                                     13
F 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                                                                                                                                           15
Product 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 Poor
development 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                                                                                                                                                                                                     17
F 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 Landscape
at 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                                                                                                                                            19
Biotechnology 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 Poor
You can also read
Next part ... Cancel