How should Australia do global health R & D? Invest in PDPs to develop new health tools

HIV/AIDS TB Malaria NTD Diarrhea Respiratory

Diagnostics

Microbicides &preventatives

Therapeuticproduct

Vaccine Human hookworm vaccine initiative

Vaccine Development

Program

PDPs work across different diseases and modalities

&Source:

Product Development Partnerships (PDPs): Filling the Gaps in Translational Research and Product Development

Product Development Partnerships (PDPs)

Goal: to find solutions for diseases causing the greatest burden of sickness and death amongst neglected patients In neglected health systems

build global partnerships with complementary, strengths.

discover, develop, and deliver cost-effective health tools

0 2 4 6 8

7Feasibility

7TestDevelopment

6Evaluation

1Demonstration

6CountryAdoption

CD4FINDIDRI

Notes: Includes products not funded by Gates Foundation. Biopharmaceutical candidates in development Include: IAVI, IPM, IVI, GATB, Aeras, MMV, MVI, MVP, PVS, DNDi, iOWH, PDVI, HHVI.Source: PDPs

4%

22%

26%

22%

7

5

0 2 4 6 8

Early Stage

InDevelopment

IVCC

# candidates

Diagnostics

Vector control

26%

Pipeline Now Begins to Be Filled 143 Candidates

59Pre Clinical

15Phase I

12Phase II

10Phase III

2Registration

6Launched

DrugsVaccinesMicrobicides

# candidates

10%

12%

14%

57%

6%

2%

&Source:

104 biopharmaceutical candidates in development…

…and 39 diagnostic & vector control candidates

Successes of PDPs

Successes of PDPs

New tools to combat diseases in low- and middle-income countriesmalaria sleeping sickness cholera Japanese encephalitismeningitis visceral leishmaniasis tuberculosis Chagas disease

19 new products produced by PDPs

1. ASAQ (artesunate/amodiaquine) (DNDi) 11. KalazarDetect (IDRI)

2. ASMQ (artesunate/mefloquine) (DNDi) 12. Paromomycin (iOWH)

3. NECT (Nifurtimox Eflornithine Combination Therapy) (DNDi) 13. Killed whole-cell oral cholera vaccine (IVI)

4. SSG&PM Combination Therapy in Africa (DNDi) 14. Coartem® Dispersible (MMV w/Novartis, reg. by

SwissMedic)

5. Xpert MTB/RIF (or automated nucleic acid amplification) (FIND) 15. Injectable artesunate (MMV with Guilin

6. Liquid culture (FIND) Pharmaceuticals)

7. Rapid speciation for MDR-TB (FIND) 16. MenAfriVac (MVP)

8. LPA line probe assay (FIND) 17. JE Vaccine India (PATH)

9. Fluorescence microscopy (FIND) 18. Paediatric formulation of benznidazole (DNDi)

10 Eurartesim DHA-Piperaquine (MMV) 19. Leishmaniasis combination treatments in Asia (DNDi)

Therapeutic Product PDPs

Start with Disease Strategy defined by End Users

A Disease Strategy specifies:

Tool box vs. Single tool Drugs, Vaccines, Diagnostics Treatment strategies (MDA vs Case Management)

Commitment to a product from discovery

research through to patient access

End Users define Research Strategy

Major Role of Regional DiseasePlatforms: Defining patients’ needs and

target product profile (TPP) Strengthening local

capacities Conducting clinical trials

(Phase II/III studies)

Facilitating registration Accelerating implementation

of new treatments (Phase IV & pharmacovigilance studies)

HAT

VL

CHAGAS

Bes

t Sci

ence

for t

he M

ost N

egle

cted

Commitment from Discovery to Access

December 2011

Discovery Translational Clinical Implementation

Nitroimidazole backup (HAT)

Nitroimidazole backup (HAT)

Oxaborole backup (HAT)Oxaborole backup (HAT)Scr

eeni

ngS

cree

ning

Scr

eeni

ngS

cree

ning

Con

solid

ated

Lea

d O

ptim

isat

ion

VL-2098 (VL)VL-2098 (VL)

Alternative formulations of Amphotericin B (VL)

Alternative formulations of Amphotericin B (VL)

Nitroimidazole backup (VL)

Nitroimidazole backup (VL)

Fenarimol series (Chagas)Fenarimol series (Chagas)

K777 (Chagas)K777 (Chagas)

Flubendazole -Macrofilaricide (Helminth)

Flubendazole -Macrofilaricide (Helminth)

Improved PI for 1st-line• Prodrugs of LPV/RTV• New formulations of LPV/r

Improved PI for 1st-line• Prodrugs of LPV/RTV• New formulations of LPV/r

Fexinidazole (HAT)Fexinidazole (HAT)

Oxaborole SCYX-7158 (HAT)

Oxaborole SCYX-7158 (HAT)

New VL treatments –Bangladesh

New VL treatments –Bangladesh

New VL treatments – Africa AmBisome® MiltefosineNew VL treatments – Africa AmBisome® Miltefosine

New VL treatments –(Latin America)

New VL treatments –(Latin America)

HIV / VL HIV / VL

Azoles E1224 & Biomarker (Chagas)

Azoles E1224 & Biomarker (Chagas)

Benznidazole Paed. dosage form (Chagas) Benznidazole Paed.

dosage form (Chagas)

NECT (Stage 2 HAT) Nifurtimox - Eflornithine

Co-administration

NECT (Stage 2 HAT) Nifurtimox - Eflornithine

Co-administration

SSG/PM co-administration

VL in Africa

SSG/PM co-administration

VL in Africa

New VL treatments in Asia

(SD AmBisome®,3 drug combinations)

New VL treatments in Asia

(SD AmBisome®,3 drug combinations)

✓: NCE

✓

✓

✓✓

✓

✓✓

✓

✓

✓

✓HATHAT

LeishmaniasisLeishmaniasis

ChagasChagas

HelminthsHelminths

Paed. HIVPaed. HIVASMQ Fixed-Dose

Artesunate/ MefloquineASMQ Fixed-Dose

Artesunate/ Mefloquine

ASAQ Fixed-Dose Artesunate/ Amodiaquine

ASAQ Fixed-Dose Artesunate/ Amodiaquine

MalariaMalaria

10

TafenoquineGSK

MMV Drug Development Portfolio, 4Q 2011:Significant Australian Footprint at All Stages of R&D

RegistrationPreclinicalResearch* Translational Development

Lead Opt Phase IIaPhase ILead Gen Phase IVPhase IIb/III

Novartisminiportfolio

Novartis2 Projects

MK4815(Merck)

Artesunate for injection

Guilin

Coartem®-DNovartis

GSKminiportfolio

Broad/Genzymeminiportfolio

OxaborolesAnacor

Other Projects15 Projects

sanofi aventisOrthologue screen

KinasesMonash

PfizerScreening

GSK2 Projects

NITD609Novartis

OZ439(Monash/UNMC/

STI)

Azithromycin chloroquine

Pfizer

PyramaxShin Poong/University

of Iowa

ASAQ Winthropsanofi aventis/DNDi

AminopyridineUCT

QuinolonesUSF/ OHSU-VAMC

PyrazolesDrexelMed/UW

AstraZenecaScreening

GNF156Novartis

DSM265(UTSW/UW/

Monash)

AminoindoleBroad/Genzyme

Eurartesim sigma tau

AnitmalarialsSt

Jude/Rutgers/USF

P218 DHFRBiotec/Monash/LSHTM

AntimalarialsDundee

DHODHUTSW/UW/

Monash

PyramaxPaediatric

Shin Poong/University of iowa

Australian contribution to MMV science projects

Included in MMV portfolio at Phase IV

Targeting P. vivax

Source: MMV, March 2012

* In addition to individual projects listed here, Australian Research teams are contributing specific capabilities to virtually every MMV Research project, including:• High-throughput screening P. falciparum• Gametocyte assay

• P. vivax ex vivo field testing• Drug metabolism and pharmacokinetics

Dedicated Teams WorldwideOver 550 People Committed to DNDi’s Vision

30

40

200

100

90

80

15

Chagas Lead Optimization ConsortiumFrom a hit to a potential pre-clinical candidate

Key partners:

AUSTRALIA:

- CDCO/Monash University,

- Epichem, Murdoch University

SOUTH KOREA:

- Institut Pasteur Korea

Global network to address a global burden

DNDiPartnership of the Year

2011

13

MMV Current Science Collaborations In Australia IncludeWorld Class R&D Centers and Several CROs

Source: MMV, March 2012

Brisbane• Griffith University (Vicky Avery)• Queensland Institute of Medical

Research – QIMR(James McCarthy)

• Australian Army Research Institute(Dennis Shanks)

Sydney• Sydney University

(Todd Matthew)Melbourne

• Melbourne University (Julie Simpson)• Monash University (Andrew Wilks, Sue & Bill Charman)

Research Institute / University

Contract Research Organization

Adelaide• INCResearch Australia• CMAX• CPR

• Nucleus Network

• Q-Pharm• Q-Pathology

Darwin• Menzies School of Health Research

(Ric Price)

(Italics) Lead Researcher

Why are PDPs Good Investments?

Created largest global health product development pipeline ever for drugs, vaccines and diagnostic tools.

Ensure patient access to research outcomes

Part of the overall investment in health research that greatly boosts local and national economies.

Build and strengthen capacity of people and institutions in developing countries

Cost effectiveness

Estimates are $800 million to $2 billion (USD) for the pharma industry to develop one new drug.

DNDi developed 4 new treatments and research pipeline with $125 million (USD)

PDPs leverage funding to secure inkind contributions from pharma

Sustaining the Momentum

Many products are advancing to late-stage development…

Costs will be saved in the long run… with the deployment of cheaper diagnostics, drugs and vaccines

AND significant savings will accrue as populations grow healthier

HOW SHOULD AUSTRALIADO GLOBAL HEALTH R&D?

ANU

Dr Mary MoranExecutive Director, Policy Cures

WHAT DO YOU NEED?

Source: G‐FINDER 2011, Independent Review of Aid Effectiveness, 2011* Estimate 

Innovative solutions for global healthMedical research Pub/Pop health 

research

Pub/Pop health research

Basic research

Product R&D

Medical operational research

$9m• NHMRC = $6.8m, 74%• DIISR = $2.4m, 26%• AusAID = nil Australia's current role

Current spend on research

Unknown• NHMRC ??• AusAID ??

>$24m• AusAID – $24m*• Others – ??

$23m• NHMRC = $18.4m, 80%• DIISR = $4.4m, 20%• AusAID & ADF = <$0.2m, <1%

CURRENT INVESTMENTS LEAVE A PRODUCT R&D GAP

Source: G‐FINDER

Australia public sector funding by type of research, 2007‐2010

a widening gap…

68% 

60%  65% 

71% 

32% 

40% 

35%  29% 

0

5

10

15

20

25

2007 2008 2009 2010

Millions (A

U$)

Basic research Product developement

WHY SHOULD AUSTRALIA INVEST IN GLOBAL HEALTH RESEARCH& DEVELOPMENT?  THE EXAMPLE OF VACCINES

Global mortality in children under five years

Global Immunization, DPT3 coverage in 2009

In the next decade, estimated to:• Prevent over 400,000 cases• Save 44,000 lives• Avert 105,000 disabilities

INNOVATIVE SOLUTIONS CAN BE GAME‐CHANGERS –MENAFRIVACTM MENINGITIS A

TOOLS ARE ON THE WAY (VACCINE EXAMPLE)

Number of candidates in Phase II (54)

Bacterial pneumonia and meningitis (104.6m DALYs)

3

Diarrhoeal diseases (72.3m DALYs)

7

HIV/AIDS (57.8m DALYs) 16

TB (34m DALYs) 6

Malaria (33.9m DALYs) 17

Dengue (663,000 DALYs) 1

Salmonella infections  4

Number of candidates in Phase III  (12)

Bacterial pneumonia and meningitis (104.6m DALYs)

1

Diarrhoeal diseases  (72.3m DALYs)

4

HIV/AIDS (57.8m DALYs) 3

TB (34m DALYs) 1

Malaria (33.9m DALYs) 1

Schistosomiasis (1.7m DALYs) 1

Dengue (663,000 DALYs) 1

December 2011

THE MEDICAL R&D POLICY GAP

What is needed is the funding to bring these products to 

completion 

… CANNOT FUND EVERYTHING

• Many diseases, many choices• scientific challenges and risks• health impacts• timelines

• Government agencies have own priorities, agenda

• Australian researchers have certain strengths

A MEDICAL R&D INVESTMENT ROADMAP

IDENTIFY GLOBAL HEALTH NEEDS AND OPPORTUNITIES(CONSULTATION)

SHORTLIST THOSE THAT BEST MATCH EACH AGENCY’S AGENDA

PUBLISH ROADMAP

RESEARCHERS APPLY/ RESPOND

GOVERNMENT EVALUATES AND INVESTS

Outcome:

INNOVATIVE SOLUTIONS DEVELOPED THAT MATCH AUSTRALIA’S PRIORITIES

Australian Govt agencies

NHMRC

Work with best researchers –Australian and international

Aust researcher

PDPs

DIISR

Basic research

Product development

AusAID

PDPsPDPs

International researcher

Aust researcher

Industry

International researcher

THE ROADMAP STAKEHOLDERS

Aust researcher

Operational  research

Thank you

Recommendation 23: How should Australia do global health R&D

PREVENTATIVE HEALTH FLAGSHIP

Graeme Woodrow PhD FTSE FAICD 20 March 2012

Key Points

Research is important, seriously!

“Research ain’t Research” – the type of research is important

“United we stand” – the need for greater interconnectedness

Research is important, seriously!

‐ Research to a researcher is like water to a fish‐ But not everyone is of the same view

‐ e.g. Treasury staff ‐ Is R&D necessary for innovation?

‐ Research needs to be understood as critical to “core business”

‐We need good arguments and lots of examples of why research is critical.‐ e.g. continuous improvement, removing bottlenecks to implementation, maintaining international best practice, etc

‐Maybe we need research on research.

“Research ain’t Research” – the type of research is important

Sir Mason Durie talks of “dual accountabilities”:– To science, to the science community, to scientific merit– To community knowledge, to the local community, to translational merit

Research that makes a difference

• Understand need and develop and test solutions with local communities

• Identify most successful approach and scale it up

Action Research

Implementation Science

Example is B4MD – bringing local communities, business and researchers together in Indonesia

Challenge to traditional research process

Challenge to researchers – must work with local communities and/or delivery partners from outset

Challenge to funders – not your traditional grant –“where are the milestones?”

This requires trust developed through long term partnerships

Principles underpinning initiativesWhole of system understanding

Community‐based and guided

Emphasis on families and communities

“Co‐creational” vs Observational

Research that creates new knowledge AND makes a lasting difference to community

Integrating public health and clinical/biomedical, i.e. combining prevention and treatment 

Responsive and flexible, i.e. based on principles of Implementation Science rather than RCTs

Long term

Emphasis on equity, ensure programs target the deprivation gradient

Multidisciplinary project – low cost diagnostic for detecting infectious diseases from breath and urineRobust, simple sensors

Algorithms and data processing

Mobile phone as reader and apps integrator

Integrated diagnostic

tool

We understand the need but we don’t understand the pathway to marketMarket access through PDPs

The Global Research Alliance (GRA)

“United we stand” – the need for greater interconnectednessWe share common goals, but operate in different cultures

– Physical and social sciences– Public and private– Research and delivery– Public health and clinical– Services and products

Competitive funding model builds competitive culture

Challenges are multi‐faceted and multi‐layered requiring collaboration

Funders hear multitude of self interest

Need for an Australian Global Health Researchers’ AllianceFocus on:

‐ Development of a coherent and aligned research agenda allowing larger collaborative programmes

‐ United and well articulated call for growth of funding

Progress

- Consultation process underway

- Interim leadership group meeting soon

- Establishment in 2012

Collaboration

“Think of what we could achieve when we don’t care who gets the credit.”

- Geoff Garrett, CEO CSIRO, 2000-2008

Thank youP‐Health FlagshipGraeme Woodrow

t +61 2 9490 8232e graeme.woodrow@csiro.auw www.csiro.au/

P-HEALTH FLAGSHIP

How should Australia do global health R&D?

Stephen Howes20 March 2012

Australia is no longer a small donorAid relative to the median among the top 15 donors, 2005 and 2012 (est.)

Source: OECD DAC, Development Policy Centre

0

0.5

1

1.5

2

2.5

3

United Stat

es

United King

domSwitz

erlan

dSwed

enSpa

inNorw

ayNetherl

ands

Japa

nIta

lyGerm

any

France

Denmark

Canada

Belgium

Austra

lia

2005 2012

(4.1,3.6) (3.5)

Key funding principles and choices

Funding principles• Maximize value for money • Minimize management burdenFunding choices• Team Australia or Team world?• Fund inputs, outputs or outcomes?• Management arrangements?• Big or small?Existing situation• $20m+ a year from NHMRC

Choice 1: Team Australia or Team World

• The approach followed to date (NHMRC)• Agricultural research follows a team Australia approach

– Recent ACIAR review explicit about this.– Most ACIAR funding involves Australian researchers; a small 

amount for global research institutions.• Advantages: 

– Geographical rationale for agriculture, but not for medicine.– Political buy‐in– Good if international institutions not functioning well

• Disadvantages:– Protectionist (tied aid)– May not give value for money

Choice 2: Inputs, outputs or outcomes

• Most medical research funding is input based– PDPs

• But there are alternatives– Advance Market Commitment: output based– Health Fund: outcome based.

• Results‐based aid is attractive, but has its disadvantages– Output‐based approach: Very difficult to specify the output. This 

probably explains very limited use of this approach.– Outcome‐based approach: Requires 20 year commitments, 

which are very difficult to make credible.

Choice 3: Management arrangements

• AusAID? – No expertise, stretched, but quick and cheap

• NHMRC?– Already funding global R&D– Appropriate for a Team Australia approach

• ACIHR?– Establish a new body (to parallel ACIAR)– A lot of work, with limited rationale?

Choice 4: Big or small?• Arguments for rapid scale up depend on how you scale up.– Ease of management– Stresses of overall scale up

• Aid review argued for greater reliance on effective multilateral agencies for precisely these reasons.– Allows a performance‐based, transparent, hands‐off, results‐oriented approach to be taken with minimal management burden.

– This is what our approach to global health R&D should look like.

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Global health R&D funding Total ODA

SwitzerlandSpainNorwayNetherlandsSwedenAustraliaGermanyFranceUKUS

Share of global health R&D among top 10 OECD funders (2010), and share of

total ODA among the same 10

Global health R&D to total ODA for top 10 OECD funders

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

7.0%

US UKFrance

Germany

Austra lia

SwedenNetherla

ndsNorway

SpainSwitze

rland

Source: Policy Cures G-Finder 2011; Development Policy Centre

Conclusion• Substantial NHRC funding already in place for global medical 

R&D will presumably continue. • Value for money considerations support a shift towards a 

“Team World” approach if an expanded budget for global R&D is available.

• If we are happy with an input based approach, this in turn points us to the Product Development Partnerships as a suitable vehicle.

• This in turn would have light management requirements, avoiding the need for a separate management institution, even if we want to go in big (as we should).