Neglected eg ectedTropical Diseases: Why should we care?

Presented by:Dr. Olawale SalamiClinical Project ManagerDrugs for Neglected Diseases initiativeAt the Media Briefing Workshop, Kigali Rwanda28th November 2018

WhyWhy Neglected?

Common features of Neglected tropical didiseases• Many of the neglected tropical diseases are disfiguring and y g p g g

stigmatizing.• They affect the poorest of the poor, with few or no 

i l k t f d d i i t thcommercial markets for drugs and vaccines against them.• The pharmacopoeia for these diseases has remained 

essentially unchanged since the middle of the 20th century.y g y

What are NTDsA group of infectious diseases that affect more than one billion people and cost developing economies billions of dollars every year

The diseases are found in tropical and subtropical conditions in 149 countries 

Populations living in poverty, without adequate sanitation, and in close contact with infectious vectors and domestic animals and livestock are those worst affected.

3 billion people are at risk of neglected tropical diseases 1 billion3 billion people are at risk of neglected tropical diseases, 1 billion affected

170,000 people will die by the end of each year from these diseases

There are 20 diseases in the WHO NTD list including mycetoma, added in 2016, as well as chromoblastomycosis and other deep mycoses, scabies and other ectoparasites and snakebite envenoming which were added in 2017other ectoparasites and snakebite envenoming which were added in 2017.

Global distribution of NTDs.

Approximately 1 billion people are affected by more than one of NTDs

WHO’s List of Neglected tropical Diseases

1. Dengue2. Rabies

12. Taeniasis and neurocysticercosis13. Echinococcosis

3. Trachoma4. Buruli ulcer5. Yaws

14. Foodborne trematodiases15. Lymphatic filariasis16. Schistosomiasis

6. Leprosy7. Chagas disease8. Human African trypanosomiasis 

17. Soil‐transmitted helminthiases18. Mycetoma, 

chromoblastomycosis and other (sleeping sickness)

9. Dracunculiasis (guinea‐worm disease)

deep mycoses,19. Scabies and other 

ectoparasites10. Leishmaniasis11. Onchocerciasis (river blindness)

20. Snakebite envenoming

Trachoma

Blinding trachoma, caused by a bacterium, chlamydia trachomatis, affects more than 80 million people around the world. Children are mainly concerned by the infection, 

d 4 l bli d f h 3 Af i i h i i h hand every 4 people blind from trachoma 3 are women. Africa is the continent with the greatest number of endemic countries, but America, Middle‐East and Asia are also endemic. SAFE strategy (Surgery, Antibiotics, Facial cleanliness, Environmental improvement) has proven its effectiveness in eliminating this scourge from humanity.improvement) has proven its effectiveness in eliminating this scourge from humanity.

Lymphatic filariasis (LF)O 120 illi l tl i f t d d d 1 3 billi l iOver 120 million people are currently infected and around 1.3 billion people in more than 80 countries are at risk of infection. Drugs used against lymphatic filariasis are either donated – albendazole and ivermectin, or very inexpensive DEC Albendazole is donated to WHO by GlaxoSmithKline for massDEC. Albendazole is donated to WHO by GlaxoSmithKline for mass administration to at‐risk populations.

Guinea-worm diseaseThe disease exists only in Africa and is transmitted exclusively by drinking contaminated water. 

Global progress in eradication linked to increased availability of safe drinking p g y gwater in endemic regions.

LeishmaniasisLeishmaniasis is a parasitic disease caused by the Leishmania parasite. ThisLeishmaniasis is a parasitic disease caused by the Leishmania parasite. This parasite typically lives in infected sand flies. You can contract leishmaniasis from a bite of an infected sand fly. The sand flies that carry the parasite typically reside in tropical and subtropical environments..p p

Visceral leishmaniasis Cutaneous leishmaniasisPost‐kala azar dermal leishmaniasis

MycetomaMycetoma is a bacterial or fungal infection that can be devastating, and can result  in amputation.Research on mycetoma is scarce & incidence unclear. However, prevalence of 14.5 per 1,000 reported in endemic areas

Disease Burden of the Neglected Tropical Diseases in Deaths and DALYs

Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, et al. (2006) Incorporating a Rapid‐Impact Package for Neglected Tropical Diseases with Programs for HIV/AIDS, Tuberculosis, and Malaria. PLOS Medicine 3(5): e102. https://doi.org/10.1371/journal.pmed.0030102https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0030102

Comparative Disease Burdens of Communicable Diseases Measured in DALYsDiseases Measured in DALYs

Hotez PJ Molyneux DH Fenwick A Ottesen E Ehrlich Sachs S et al (2006) Incorporating a Rapid Impact Package for Neglected Tropical DiseasesHotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, et al. (2006) Incorporating a Rapid‐Impact Package for Neglected Tropical Diseases with Programs for HIV/AIDS, Tuberculosis, and Malaria. PLOS Medicine 3(5): e102. https://doi.org/10.1371/journal.pmed.0030102https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0030102

Economic impact of NTDs• High endemicity in rural and in impoverished urban areas of low‐income countries.

• Significant ability to impair childhood growth, intellectual development, and education.

• Reduced  worker productivity. 

In this way, the neglected tropical diseases     y     g   p    are poverty‐promoting conditions. 

Economic impact of NTDs: filariasis• Lymphatic filariasis is most 

prevalent in working aged ki h imen, making the economic 

impact of this disease significant.

• Affected patients lose as much as 11 years of productivity, mainly in the agricultural sector.

• Cost per patient treated is no higher than $2.23 and the economic return is between $20 ‐ $60

Ref: Social and Economic Impact Review on Neglected Tropical Diseases November 2012, Hudson Institute.

Psychosocial burden of NTDs“Before this disease, I walked around easily 

d i dand carried out my activities the with ease. Nowadays I rarely visit my friends. I don’t want y fto be a burden to them”Zainab IbrahimMycetoma Patient

• Discrimination and poverty  are both causes and p yconsequence of NTDs.

• The psychosocial burden and stigma associated with life long disfigurement of some NTDs is frequently overlookedlong disfigurement  of some NTDs is frequently overlooked.

Neglected tropical diseases (NTDs):a right to health issuea right-to-health issue NTDs almost exclusively affects poor and marginalized people 

in low‐income countries, in rural areas and settings where poverty is widespread

Health interventions and research and development have longHealth interventions and research and development have long been inadequate and under funded and the picture has changed only in recent years.

Some of the essential drugs against NTD are now available but other are still inadequate or unavailable.

Addressing NTDs is vital towards attainment of the SDG 3 andAddressing NTDs is vital towards attainment of the SDG 3 and others.

What is the l ti hi

18

relationship between 

environmentalenvironmental change and 

neglected tropicalneglected tropical diseases?

Environmental change and NTD transmission

b hHuman behaviorVectors, pathogens and hosts each survive and 

Vector biology 

Environment

reproduce within a range of optimal climatic conditionsclimatic conditions (temperature, humidity etc)

Disease transmission

humidity etc)

Predicting the impact of Environmental change and NTD transmission

http://www.who.int/globalchange/climate/en/chapter6.pdf

Can we What21

Can we indeed eradicate

What  successes 

anderadicate neglected 

and challenges 

tropical diseases?

of current efforts?

Yes its possible to eradicate NTDs22

Control with current toolsDiagnostic procedures are not sensitive

Paris – 11 septembre 2006What do we need?Simple, efficient and                     

inexpensive diagnostic tools

Oral inexpensive drugs that do not

Diagnostic procedures are not sensitive, cannot be used at field level and are 

expensive

Oral, inexpensive drugs  that do not have side‐effectsTreatment is costly, difficult to 

administer, can have serious side‐effects and can become resistant

Integration within existing health structures is possible

Need for specialized services structures is possible

Integration is not possibleservices

Sustained control/elimination is feasibleSustained control/elimination is difficult

Preventive chemotherapy Existing field-applicable tools

Simple, cheap community diagnosisLarge scale treatment of groups or communities in needLarge scale treatment of groups or communities in need

Regular "preventive" treatment

Coordinated use of a few drugswill have an impact on many diseases

Sustained control / elimination

Persistence of the fatal imbalance

1975‐1999 2000‐2011

• 1.1% of new products for NTDs, malaria  • 756 products registered (excluding vaccines and TB  

• But 12% of global disease burden& biologicals) 

• 1% of 336 new chemical entities approved for NTDs, malaria and TB

• 1% of 148,445 clinical trials registered for

Sources: Fatal Imbalance: The Crisis in Research and Development for Neglected Diseases, MSF, 2001Pedrique B et al. The drug & vaccine landscape for neglected diseases (2000-11) Lancet Global Health, Oct 2013

1% of 148,445 clinical trials registered for neglected diseases

DNDi’s Response

DNDi, a new model for drug development created in 2003

• Non‐profit drug research & development (R&D) organization founded in 2003

• Addressing the needs of the most neglected patients

• H i f bli i tit ti i t i d t d hil th i titi

8 regional offices workingclose to patients in:

• Harnessing resources from public institutions, private industry and philanthropic entities

close to patients in: Brazil, Democratic Republic of Congo, Kenya, South Africa, Malaysia, India, Japan, USA

Founding PartnersIndian Council for Medical Research (ICMR), Kenya Medical Research Institute (KEMRI)Research Institute (KEMRI), Malaysian MoH, Oswaldo Cruz Foundation Brazil, Médecins Sans Frontières (MSF), Institut Pasteur France, WHO/TDR (permanent (pobserver)

DNDi’s Mission

• To develop new drugs or new formulations of existing drugs for people suffering from neglected diseasesfor people suffering from neglected diseases. 

• To develop drugs for the most neglected diseases (such as sleeping sickness, leishmaniasis, and Chagas disease), whileconsidering engagement in R&D projects for other neglected patients (e.g. malaria, paediatric HIV, filarial infections)infections) 

• To strengthen capacities in a sustainable manner, including through know‐how and technology transfers in the field of d & f l d didrug R&D for neglected diseases.

• To adopt a dynamic portfolio approach

Responding to the needs of patients suffering from neglected diseases

Sleeping sickness

HepatitisC

©Sa'adiaKh

an‐M

SF

DNDi’s PRIORITY: DNDi’s PRIORITY: MalariaMycetoma

Neglected Patients

Neglected Patients

PaediatricHIV

Chagasdisease

Filarialdiseases

Leishmaniasis

+ incubation with WHO of: 

…from bench to bedside

DNDi’s success is only possible through innovative partnerships Universities

& Research

PDPs

Int. Org.& NGOsBi hthrough innovative partnerships & Research

Institutes& NGOsBiotechs

CROs Pharmaceutical companies

CRITERIA FOR SUCCESS

Over 160 partnerships worldwide

CRITERIA FOR SUCCESS Share the same vision Mutual understanding Involvement throughout the 

whole process 

Some of DNDi’s Open Innovation Projects   NTD Drug Discovery Booster,  Est. 2015 Open Synthesis Network,  Est. 2016

The Mycetoma Open Source project (MycetOS),  Est. 2017

Anybody & Everybody!Anybody & Everybody!

8 new treatments delivered since 2007 Easy to use Affordable Field‐adapted Non‐patented

2007 ASAQMalaria>500 million patients reached

2011 PAEDIATRIC BENZNIDAZOLEChagas diseaseTwo sources developedp

2008 ASMQMalaria

2011 NEW VL TREATMENT ASIAVisceral leishmaniasis in AsiaMalaria

Used in Africa and Asia

2009 NECT

Visceral leishmaniasis in AsiaSupport to disease elimination

2016 SUPERBOOSTER THERAPY2009 NECTSleeping sickness100% of stage‐2 patients

2016 SUPERBOOSTER THERAPYPaediatric HIVRecommended by WHO

2010 SSG&PMVisceral leishmaniasis in E AfricaNow 1st line in all countries

2018 FEXINIDAZOLESleeping sicknessApproved by European Medicines Agency first all‐oral treatmentAgency, first all‐oral treatment

The R&D landscape for neglected patients h h d b t l till ihas changed but large gaps still remain

• R&D priorities do not sufficiently originate from low‐ and middle‐income countries

• Patients’ needs are not prioritized (e.g. Ebola, mycetoma, etc.)

1

2 Patients  needs are not prioritized (e.g. Ebola, mycetoma, etc.)

• Innovation is not linked to equitable access even when there is commercial incentive to drive innovation (e.g. HCV)

2

3

• Market incentives aligned with IP/exclusivity do not adequately address health needs in LMICs (e.g. AMR)4

These are the fundamental challenges for the future of biomedical innovation.

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