Ricerca medica indipendente

Nicoletta DenticoHealth Innovation in Practice (HIP)La Sapienza, Roma, 4 aprile 2014

Accesso ai Farmaci Essenziali

OMS, 1977: il TRS 615

• TRS (Technical Report Series) 615, destinato a fare storia come best seller dell’OMS, ben presto diventa uno degli snodi esemplari del rapporto tra salute e sanità, pubblico e privato, economia e diritto: IL PROGRAMMA DEI FARMACI ESSENZIALI

• Il significato della parola ESSENZIALE, che rimanda, senza specificare, a radici, progetti, obiettivi da raggiungere

la rivoluzione pacifica dell’OMS

Sono essenziali quei farmaci che sono di più grande importanza, di base, indispensabili, necessari pe ri bisogni di salute della maggioranza delle popolazioni dei diversi Paesi, a costi, e con condizioni di approvvigionamento, che siano compatibili con un’accessibilità corrispondente a quella auspicabile-necessaria per identificare, definire e farsi carico dei problemi-bisogni per I quali I farmaci hanno un’indicazione adeguatamente documentata

La Lista dei Farmaci Essenziali (1978)

Il 10/90 GAP

• The 1990 Commission on Health Research for Development made the first estimates of worldwide spending on health research and development (US$30.0 billion) and in analysing the flows of resources described what became known as the “10/90 gap” – capturing the inequality revealed in their estimate that: less than 10 per cent of the global budget for health R&D was being spent on 90 per cent of the world’s health problems

Non solo malattie infettive Le morti nel mondo per cancro

Decenni di enormi progressi nel campo della scienza e della tecnologia

>50 y of parasitology:

targets, inhibitors, cytotoxic

compoundsMigliaia di pubblicazioni, ma solo pochi farmaci contro le malattie tropicali

Quali farmaci per le malattie tropicali dimenticate?

• Non efficaci (resistenze)

• Tossici• Costosi• Di dolorosa

somministrazione• Difficili da

monitorare• Non adatti ai sistemi

sanitari dei paesi poveri

• Non registrati nelle regioni endemiche

• Restrizioni dovute alla protezione brevettuale

Launch & utilization

CHALLENGE 3

CHALLENGE 4

Specific

ActivitiesOrganizations

TDR

Unspecified

GSK

WRAIR

La ricerca per le malattie dimenticate nel 2000: il deserto

Screening

Lead identification

Lead optimization

In vivo efficacy

Regulatory toxicity & safety

Phase 1

Phase 2

Phase 3

Registration

CutaneousLeishmaniasis

CHALLENGE 1

CHALLENGE 2

VisceralLeishmaniasis

HAT Chagas

CHALLENGE 3

Launch &utilization

CHALLENGE 4

2007 Drug R&D Landscape for NTDs

Screening

Lead identification

Lead optimization

In vivo efficacy

Regulatory toxicity & safety

Phase 1

Phase 2

Phase 3

Registration

Launch & utilization

HAT Chagas VisceralLeishmaniasis

CutaneousLeishmaniasis

Dengue Malaria TB

CHALLENGE 1

Sandler Center

IOWHMMVGSK

DD@D

CDNDTB Alliance

DNDi

Specific

ActivitiesOrganizations

TDR

NITD – PC dengue, TB

CHALLENGE 2

CHALLENGE 3

CHALLENGE 4

Unspecified

BuruliUlcer

Intestinal helminth

WRAIR

BONO

MSF

250 PPPH WEFPHA

World Bank

http://www.dndi.org/index.phphttp://www.dndi.org/index.php

Ensure Sustainability

Critical Challenges for Product Development Partnerships

Generate Leads

Optimise Leads

Clinical Trial Capacity to Test New Drugs or Regimens

Pragmatic ID and

selection of

candidates from

existing compounds

Deliveringproducts to neglected population

s

Challenge 1

Clinical AVAILABLEto patients

ScreeningLead

selection

DiscoveryPre-Clinical

Lead optimisation

Challenge 3 Challenge 4Challenge 2

Challenge 5

The benefit of using global networks: creative harnessing of fragmented knowledge

DNDi

Sharing of experiences between

South-South LEAP scientits

CIPIH Report http://www.who. int/intellectualproperty/en/

Diagnosi e raccomandazioni dell’OMS per garantire la ricerca medica essenziale

“Innovation is pointless in the absence of favourable conditions for poor people in developing countries to access existing, as well as new, products”

“The market is not a determinant of value “

Il valore aggiunto delle Product Development Partnerships (PDPs)

PDPs possono fungere da motore, in termini di leadership scientifica;

PDPS hanno un ruolo determinante nella identificazione delle piste di R&D da seguire, e per natura possono più facilmente superare eventuali strozzature nel processo di favorire l’accesso ai farmaci ai pazienti che ne hanno bisogno

PDPs reppresentano una nuova opportunità affinché big pharma re-focalizzi la sua ricerca verso i bisogni dei paesi in via di sviluppo”

PPPs sono una nuova ed efficace strategia per portare avanti la ricerca che serve ai paesi impoveriti, sfruttando la diversità degi attori che riescono ad agggregare.

Il valore aggiunto delle PDPsPDPs can provide the drive and the scientific leadership + have a crucial role in identifying R&D pathways and overcome bottlenecks to get products to those in need

PPPs represent a new opportunity for big pharma to re-focus their research for developing countries

PPPs a new, effective and important means to pursue R&D relevant to developing countries, making use of a diversity of new players

After 15 years (and close to 1 billion US$):• Combined PDP pipeline including 122 candidates

– “Ripple effect”: R&D Capacity building, Developing country markets less opaque, Incentive for local industry, Regulatory networks

Challenges to build innovation and research capacities in Africa

• Public leadership to define R&D priorities• Significant investment with sustainable

funding• Ensure better access to knowledge and

promote innovative IP management policies

• Enable more adapted regulatory environment

• Transfer technology and strengthen research capacities in developing countries

Challenge to conduct clinical trials in very difficult settings

JS Dr. Jannin, WHO

GPTB

• Access to Sites

• Status of Infrastructure

• Staff Limitations

Dr. Jannin, WHO

Key question: How much is funding source determining R&D agenda / priority setting? Role of endemic countries?

How much are developing countries in the driving seat?

•Notion that PDPs are global organizations with equal representation from all regions is FALSE in most cases•Mision & Vision of PDPs is set in north with marginal input from south•“Nature of work, scope and budget decided by head offices not African researchers: executive decision-making remains outside Africa” •“....the current PPPO paradigm is fundamentally neocolonial in structure and operation and this needs to be revisited and addressed”

Big Pharma

Pro duct Development Partnerships

(PDPs)

FDA, EMA, Swissmedic, etc

Public R&D institutions and academia

At the end of the 90s a new “North Focused” architecture for R&D for health products for Neglected Diseases disproportionately affecting

developing countries begins to be shaped

Regulatory approval and standard setting

Translational research and developoment

Knowledge generation:

FundingPhilanthropic and

International development organizations

Corporate & Private

“London Declaration on Neglected Tropical Diseases: Ending the Neglect &

Reaching 2020 goals” (30 Jan.2012)

Promoters: Abbot, AstraZeneca, Bayer, Becton Dickinson, Bill & Melinda Foundation, Bristol-Myers Squibb, DNDi, Esai, Gilead, GlaxoSmithKline, Johnson & Johnson, Merck KGaA, MSD, Mundo Sano, Novartis, Pfizer, Sanofi, UKaid, USAID, World Bank http://unitingtocombatntds.org/

E l’OMS?

• Accelerating work to overcome the global impact of neglected tropical diseases. A roadmap for implementation,

Geneva, WHO, March 2012

• Sustaining the Drive to Overcome the Global Impact of Neglected Tropical Diseases: Second WHO Report on Neglected Tropical Diseases, Geneva, January 2013, http://www.who.int/neglected_diseases/2012report/en/

Quale impatto?

• Overall, the number of drugs shipped to endemic countries has increased nearly thirty-six percent over 2011 (995 million) with the amazing donation of nearly 1.35 billion in 2013;

• In the past two years, 74 countries — roughly two-thirds of all NTD-endemic countries — have developed integrated, comprehensive national NTD plans.

Fondo AIFA per la ricerca indipendente

Quale la situazione degli studi clinici non-commerciali in Italia?

I dati dell’ultimo Rapporto dell’AIFA segnalano che la percentuale di ricerca no-profit sul totale della ricerca sui farmaci in Italia, è passata dal 41,4% del 2008 al 35,7% nel 2010, fino a raggiungere un 32,3% nel 2012. E così dai 364 studi registrati nel 2008 si è arrivati a 225 nel 2012. Circa il 38% in meno.

http://www.agenziafarmaco.gov.it/it/content/la-ricerca-indipendente-sui-farmaci-0

Open Source Drug Discovery (OSDD), India: democratising research against Tuberculosis

OSDD(www.osdd.net ) : a global initiative driven by the Indian Council of Scientific and Industrial Research (CSIR) to provide affordable healthcare to the developing world. Set up in September 2008 as a platform for collaborative research, with the idea to offer a scientific venue where the best minds – scientists, doctors, research professionals, research organizations, software professionals, pharmaceutical enterprises and others with diverse expertise - can collectively endeavour to solve the complex problems associated with discovering novel therapies bacterial pathologies like TB

Open Source Drug Discovery (OSDD), India: democratising research against Tuberculosis (2)

• the financial commitment of $ 38 million granted by the Indian government, OSDD is one of the few public-funded open source initiatives dedicated to finding new affordable treatments for tuberculosis.

• The underlying vision of the OSDD platform was steered by the urgent need to replicate and test in the field of healthcare and medical science the success of open source models used in information technology and biotechnology, by initiating a similar open source model for drug discovery as a potentially competitive alternative to traditional closed propriety approach . See in this regard http://www.scribemedia.org/2010/10/11/the-ethos-of-open-source/

Big Pharma PDPs

NTD Product access & use in the context

of Endemic Country Health Systems

Reshaping of NTD Product R&D and delivery architecture

Product R&D based on ENDEMIC COUNTRY

Frameworks for: Priority setting, Knowledge generation

and access, Research collaboration, Medicines Regulation & Financing

agreements