Nicoletta Dentico

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DNDi turning neglect into action

• Nicoletta Dentico
• Policy and advocacy manager
• ndentico_at_dndi.org
• A more enabling environment medical innovation
• Berlin - 10 May 2007
• www.dndi.org

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DNDi was created in 2003
5 Regional Support Liaison Offices
7 Founding Partners
Indian Council for Medical Research (ICMR)
Coordination team Geneva consultants
Brazil
Kenya Medical Research Institute (KEMRI)
India
Kenya
Malaysian MOH
Malaysia
Oswaldo Cruz Foundation Brazil
USA
Medecins Sans Frontieres (MSF)
Japan
Institut Pasteur France
2 Project Support Offices
RDC
WHO/TDR (permanent observer)
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• Our Vision
• A virtual non-profit drug RD organization to
  develop new treatments against the most neglected
  communicable diseases
• and Mission
• Primary Objective To deliver 6 - 8 new
  treatments by 2014 for leishmaniasis, sleeping
  sickness, Chagas disease, malaria
• complementary Objectives
• Use and strengthen existing capacity in
  disease-endemic countries via project
  implementation
• Raise awareness about the need to develop new
  drugs for neglected diseases and advocate for
  increased public responsibility

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Current DNDi Portfolio, 1Q2007 22 Projects
AVAILABLE to patients
Discovery
Lead selection
Lead optimization
Screening
DHFR inhibitors, LT
FDC Artesunate-Amodiaquine, M
CP inhibitors, T
FDC Artesunate-Mefloquine, M
TR inhibitors, L T
Nifurtimox- Eflornithine, H
Microtubule inhibitors, H
NPC1161B, an 8-aminoquinoline, VL
Scynexis screening, T
Paromomycin, VL
CDRI screening, T
Imiquimod, CL
Genzyme screening, T
AmBisome, L
Kitasato screening, T
Drug combinations, VL
Amphotericin B polymer, VL
Novel nitro- heterocycles, H
L Leishmaniasis VL Visceral leishmaniasis CL
Cutaneous leishmaniasis T Trypanosomiasis C
Chagas disease H Human African trypanosomiasis
Ravuconazole, C
Ascofuranone, H
Nitroimidazoles 1, L T
Nitroimidazoles 2, H
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The global dimension of neglect
sleeping sickness, leishmaniasis, Chagas disease,
malaria, Buruli ulcera lie outside of the world
market
Global Diseases
Most Neglected Diseases
Neglected Diseases
World pharmaceutical market 602 bn in 2005
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Spending on health RD has increased

• World-wide spending on health RD was never so
  high
• Estimated at US106bn for 2004 (GFHR, 2004)
• Since 90s private sector has become biggest
  investor

US-spending on health RD(gt2/3rd total)
Sources For government National Science
Foundation 2004, http//www.nsf.gov/sbe/srs/nsf
04329/pdf/nsf04329.pdf For Industry PhRMA 2004,
http//www.nsf.gov/sbe/srs/nsf04329/pdf/nsf04329
.pdf
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New drugs developed from 1975-2004
Total 1,556
Tropical diseases 18
1.3
TB 3
Tropical diseases and tuberculosis account for
12 of the global disease burden but only 1.3 of
new drugs developed.
Source Chirac P, Torreele E. Lancet. 2006 May
12 1560-1561.
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New Product Development Partnerships
receive only 16 of funding from governments
Public sector 16
UN Agencies 3
Private sector 2
Philanthropic organizations 79
Source LSE / Wellcome Trust. The New Landscape
of Neglected Disease Drug Development. 2005.
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The PDP reality more products in pipeline but
have yet to reach patients
2000
Some with TDR collaboration Further
SME in-house activity yet to be included
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Success rate for PDPs likely to be lower (WHO
CIPIH report)

• PDPs tend to seek breakthrough products rather
  than incremental innovation (as compared to
  industry)
• Attrition rate higher in the longer term, once
  the low hanging RD fruits have been picked
• RD costs lower, but failure rates may be higher
  due to inadequate funding
• CIPIH 3.3 governments cannot passively rely
  on what these partnerships clould eventually
  deliver there is a need for stronger commitment
  on their part for an articulated and sustainable
  effort to address the research gaps

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PDPs new RD business modela non-threatening
niche or a transformational force?
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The Artesunate-Amodiaquine Fixed-Dose
Combination ASAQ 
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Rationale for the ASAQ Project

• 2002
• WHO recommends in particular the use of drug
  combinations containing Artemisinin
• Artesunate-SP
• Artemether-lumefantrine
• Artesunate-amodiaquine (AS-AQ)
• Artesunate-mefloquine (AS-MQ)

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• 2006, WHO
• strengthens
• recommendations.
• ACTS should be
• first-line treatment for falciparum malaria
  everywhere
• in fixed-dose combinations when possible

www.who.int/malaria/docs/TreatmentGuidelines2006.p
df
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DNDi ASAQ Partnership
Industrial Partner Sanofi-Aventis
Funding DNDi, MSF, TDR, EUs INCODEV, DFID,
Farmanguinhos, AFD-France, DGIS Netherlands
Scientific Coordination Project Management
DNDi/TDR
Ellipse Pharma Tropival of Uni Bordeaux,
France pharmaceutical development
CNRFP, Burkina Faso phase III clinical trial
Contractual Partners Comips, Rottendorf Pharma,
Unitox, Genotox, Créapharm, Cardinal Systems
Uni Sains, Malaysia development of analytical
methods, human animal PKs, phase I study
Center for Tropical Med Univ Oxford, UK PK/PD,
in vitro and molecular studies
Farmanguinhos, Brazil Pharmaceutical
development, animal toxicity
- - - - - - Sharing information ----------
Sharing info/data/methods/products
AS/AQ Artesunate/Amodiaquine PK/PD
Pharmacokinetics/Pharmacodynamics
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ASAQ DNDi and sanofi-aventis An Innovative
Partnership

• Since 2002, DNDi partners have ensured the
  pharmaceutical and clinical development
• DNDi licensed the product to s-a in Dec 2004
• Patent free arrangement
• Public price  at cost 
• target ltUS1 for adult, US0.50 for children
• Pediatric strenghts available
• Drug registered in Morocco
• Production in Morocco ? good science in the south
  for south

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Advantages of the AS-AQ Fixed-Dose combination

• Optimized ASAQ ratio
• to prevent over- and under-dosing
• Taylor WRJ, et al. Bulletin of the WHO. 2006
  84 956-964.
• Easy to use fewer tablets in once-a-day
  treatment regimen
• gt drugs taken together and in correct
  proportions
• Affordable lt1 for adult, 0.50 for children
• Available no patent taken

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Simplified 3-Day Dose Regimen of ASAQ
Co-blistered non-fixed ASAQ Artesunate-amodiaquin
e
NEW Fixed-dose ASAQ Artesunate/amodiaquine
AS 50 mg AQ 153 mg
3 dosage strengths available
Infants (4.5-8 kg)
AS 25 mg AQ 67.5 mg
Young Children (8-17 kg)
AS 50 mg AQ 135 mg
Children (17-35 kg)
AS 100 mg AQ 270 mg
Adults (36 kg)
AS 100 mg AQ 270 mg
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Coarsucam Artesunate Amodiaquine Winthrop
Differentiated packagings
TM
TM
Pharmacies CAP program
Public market
Artesunate Amodiaquine Winthrop
COARSUCAM Impact Malaria
Private market
COARSUCAM
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Population in millions in 31 countries where ASAQ
could be considered as 1st line treatment for
uncomplicated malaria in Africa 497.3M
1st priority countries where ASAQ is adopted as
1st line where ASAQ is one of 1st-line
treatments 2nd priority countries where ASAQ can
be of benefit
Reference RBM-WHOAfro, 2006.
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Registration FileInternational standards

• Approved in Morocco, February 2007
• Submitted to the WHO prequalification process,
  March 2007
• Registered in 12 sub-Saharan African countries
• Benin, Togo, Mauritania, Burkina-Faso, Guinea,
  Mali, Gabon, Congo, DRC, Madagascar

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ASAQ governments reactions

• Germany I am particularly pleased of course that
  the new drug will be available without any
  patents for all suppliers and patients, i.e. as a
  public good. By taking this route, all those
  involved are making an important statement about
  affordable medical care for the people in
  developing countries Minister Heidemarie
  Wieczorek-Zuel
• Italy We do welcome the public good approach
  that has inspired the partnership between DNDi
  and Sanofi- Aventis.which has produced open and
  shared innovation. This is the way to follow
  State Secretary for Cooperation, Patrizia
  Sentinelli
• UK The development of ASAQ is not only a
  wonderful breakthrough which will allow poor
  people to access effective treatment for
  malaria.  The beauty of ASAQ is its simplicity
  and the fact that it will be  non-patented. 
  This means that developing country
  governments and patients are much more able to
  afford it and I am confident that the lives
  of millions of people will be improved as a
  result of this successful and innovative
  partnership. " Gareth Thomas, UK Minister for
  International Development
•  

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G8 promises from Okinawa (2000) to Rostock
(2007)

• The conditions are right for a step change in
  international health outcomes (G8 Com. 2000)
• we therefore committo urgently deliver three
  critical targets
• - 25 reduction of HIV/AIDS infected young
  people by 2010
• - reduce TB deaths and disease prevalence by
  50 by 2010
• - reduce malaria burden of disease by 50
  by 2010

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The G8 partnership agenda

• Mobilising addditional resources to prevention
  and treatment of infectious diseases
• Promoting political leadership in health
• Working to making existing cost-effective
  interventions more universally available and
  affordable in developing countries
• Addressing the issue of access to medicines.and
  assessing obstacles being faced by developing
  countries in that regard
• Strenghtening co-operation in the area of
  research and development of new drugs, vacines
  and other international public goods

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Still a long way to go which direction to take ?

• WHO IGWG provides a historic opportunity
• to increase governments ownership about the
  requirements linked to essential health
  innovation
• political leadership is key to grant innovation
  access
• to project WHO/ government commitments, well
  beyond the mid-term framework defined by WHA
  59.24