DNDi’s antimalarial: a new public good for neglected patients

Nicoletta DenticoPolicy and advocacy manager

Drugs for NeglectedDiseases Initiative(DNDi)

www.dndi.org

Founded in July 2003 as a new collaborative, patients’ needs- driven,

not-for-profit drug R&D model for neglected

diseases

Our Vision• A virtual non-profit drug R&D 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

• Secondary 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

The DNDi team

Kenya Medical Research Institute (KEMRI)

WHO/TDR (permanent observer)

Medecins Sans Frontieres (MSF)

Malaysian Ministry of Health

Institut Pasteur France

Oswaldo Cruz FoundationBrazil

Indian Council for Medical Research (ICMR)

Kenya

7 Founding Partners

Malaysia

RDC India

Japan17 Coordination team Geneva + consultants

6 Liaison Offices

Brazil

Nifurtimox-Eflornithine, H

Novel nitro-heterocycles, H

CP inhibitors, T

DHFR inhibitors, LT

TR inhibitors, L T

Ascofuranone, H

Nitroimidazoles 1, L T

Microtubule inhibitors, H

Kitasato screening, T

CDRI screening, T

Scynexis screening, T

Genzyme screening, T

Current DNDi Portfolio, 1Q2007: 22 Projects

Nitroimidazoles 2, H

NPC1161B, an 8-aminoquinoline,

VL

Drug combinations, VL

Amphotericin B polymer, VL

Ravuconazole, C

Paromomycin, VL

FDC Artesunate-Amodiaquine, M

FDC Artesunate-Mefloquine, M

Imiquimod, CL

L: LeishmaniasisVL: Visceral leishmaniasisCL: Cutaneous leishmaniasisT: TrypanosomiasisC: Chagas diseaseH: Human African trypanosomiasis

AmBisome, L

ClinicalPre-Clinical Discovery

ScreeningLead

selectionLead

optimization

AVAILABLE to patients

World pharmaceutical market$602 bn in 2005

Neglected Diseases

Most Neglected Diseases

Global Diseases

The global dimension of neglectsleeping sickness, leishmaniasis, Chagas disease, malaria, Buruli ulcera

lie outside of the world market

• World-wide spending on health R&D was never so high – Estimated at US$106bn for 2004 (GFHR, 2004)

• Since 90’s: private sector has become biggest investor

US-spending on health R&D:(>2/3rd total)

Sources:For government: National Science Foundation 2004,

http://www.nsf.gov/sbe/srs/nsf04329/pdf/nsf04329.pdfFor Industry: PhRMA 2004,

http://www.nsf.gov/sbe/srs/nsf04329/pdf/nsf04329.pdf

0.05.0

10.015.0

20.025.0

30.035.0

1980 1985 1990 1995 2000 2005

GovernmentIndustry

Bn US$

Spending on health R&D has increased

Tropical diseases: 18

Source: Chirac P, Torreele E. Lancet. 2006 May 12; 1560-1561.

New drugs developed from 1975-2004

Tropical diseases and tuberculosis account for 12% of the global disease burden but only 1.3% of new drugs developed.

TB: 3 1.3%

Total: 1,556

receive only 16% of funding from governments

Source: LSE / Wellcome Trust. The New Landscape of Neglected Disease Drug Development. 2005.

Philanthropic organizations79%

Public sector16%

UN Agencies 3%Private sector 2%

New Product Development Partnerships

The PDP reality: more products in pipeline but have yet to reach patients

19Drugs developed since 1975 to 2000

55Drugs in development from 2000Industry 21

Industry 14

MMV 22

DNDI 6

GATB 7

TDR 11

IOWH 3

0

10

20

30

40

50

60

70

Number of drugs/projects

PPPsIndustry

21Drugs developed in past

25 years (1975-2000)*

63Drugs registered or in

development since 2000

2000

* Some with TDR collaboration** Further SME in-house activity yet to be included

Success rate for PDPs likely to be lower(WHO CIPIH report)

• PDPs tend to seek breakthrough products rather thanincremental innovation (as compared to industry)

• Attrition rate higher in the longer term, once the “low hangingR&D fruits” have been picked

• R&D costs lower, but failure rates may be higher due toinadequate funding

CIPIH 3.3: “[…] governments cannot passively rely on what these partnerships clould eventually deliver; there is a need for stronger commitment on their partfor an articulatedarticulated and and sustainablesustainable efforteffort toto addressaddressthe the researchresearch gapsgaps””

PDPs’ new R&D business model:a transformational force or a

non-threatening niche?

DNDi’s innovative partnership with Sanofi-

Aventis on the production of antimalarials

2002• “WHO recommends in particular the use of drug

combinations containing Artemisinin”– Artesunate-SP– Artemether-lumefantrine– Artesunate-amodiaquine (AS-AQ)– Artesunate-mefloquine (AS-MQ)

• For both AS-AQ and AS-MQ– No co-formulations– No partners

Malaria: Rationale for the Fixed-Dose ACT Project

DNDi’s FACT Project

Objectives• 2 fixed-dose ACTs– Easy to use: • fewer tablets in regimen•paediatric strengths•ensure drugs are taken

together and in correct proportions

– Affordable– Available as public good

AS/MQ (Farmanguinhos)

AS/AQ (s-a)

AS/AQ: DNDi and sanofi-aventisAn Innovative Partnership

• DNDi licensed the product to s-a in Dec 2004

• Public price « at cost »– target <US$1 for adult, US$0.50 for

children• Patent free arrangement• Pediatric formulations available• Drug registered in Morocco• Production in Morocco good

sicence in the south for south • WHO pre-qualification:dossier

presented in February 2007

Co-blisteredArtesunate-amiodaquine

Fixed-dose Artemether/ lumefantrine (Coartem®)

AS: 50 mg; AQ 153 mg AM: 20 mg; LF: 120 mg

15-25 kg

Not recommended* <5 kg

>35 kg

25-35 kg

AM PM

AS: 100 mgAQ: 270 mg

AS: 100 mgAQ: 270 mg

AS: 50 mgAQ: 135 mg

AS: 25 mgAQ: 67.5 mg

NEW Fixed-doseArtesunate/amodiaquine

3 dosage strengths available

5-15 kg

* A pediatric formulation of AR/LU is currently under development by Novartis and MMV

AM PM

AS/AQ: Simple 3-Day ACT Dose Regimen

Adults (>35 kg)

Children (17-35 kg)

Young Children(8-17 kg)

Infants(<8 kg)

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 importantstatement about affordable medical care for the people in developingcountries” [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 Patrizia Sentinelli]

• UK “ The development of ASAQ is not only a wonderful breakthroughwhich 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 patientsare 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 InternationalDevelopment]

ASAQ: more reactionsEuropean Parliament “I very much welcome the fact that the new ASAQ

antimalarial fixed-dose combination is born without patent. This means that, for the first time, the health of millions of people has been rated more important than profits in the creation of a new life-saving drug.

I therefore would like to offer my deepest congratulations to DNDi and Sanofi/Aventis, as you finally give us the tangible evidence that patents can be skipped in the interest of public health, especially for poor people with no purchasing power. As you know, this is a concern that all human rights organizations and the civil society worldwide have voiced for years, claiming the fundamental people’s right of access to essential health tools.

Thanks to ASAQ solution, it will be more difficult now for the big pharmaceutical companies to defend the thesis according to which it is not possible to make progress in pharmaceutical innovation, without the patent profit mechanism” [MEP Luisa Morgantini, vice-president of the EP, delegated for Africa]

Which direction do we want totake ?

IGWG provides a historic opportunity toincrease appropriation about the requirements linked to essential healthR&D, and to project WHO/ governmentcommitments globally, well beyond the mid-term framework defined by WHA 59.24.

This paper was produced for a meeting organized by Health & Consumer Protection DG and represents the views of its author on thesubject. These views have not been adopted or in any way approved by the Commission and should not be relied upon as a statement of the Commission's or Health & Consumer Protection DG's views. The European Commission does not guarantee the accuracy of the dataincluded in this paper, nor does it accept responsibility for any use made thereof.