Transcript Research Gap and Neglected Diseases

Research Gap and
Neglected Diseases
Edith Han
February 8, 2007
Access to Essential Medicines (UAEM)
10/90 Gap

“Only 10% of the world expenditure on
health R&D is spent on health conditions
that represent 90% of the global disease
burden.” (Global Forum for Health Research)
10/90 Gap
“[They] have no purchasing power, no vocal
advocacy group is pleading for their needs,
and no strategic interests—military or
security—are driving concern about these
conditions” (BMJ 325: 176–177).
Neglected Disease (ND)
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Operational Definition (FDA: U.S. Orphan
Drug Act, 1983)
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Any disease that:
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affects less than 200,000 persons in the U.S.
affects more than 200,000 persons in the
U.S. and for which there is no reasonable
expectation that the cost of developing and
making available in the U.S. a drug for such
disease or condition will be recovered from
sales in the U.S. of such drug
Neglected Disease (ND)
Neglected Disease (ND)

What NDs have in common:
They affect the world’s poorest people (and
are a cause of poverty)
 They are often vector-borne or parasitic
 Disabling, disfiguring, and stigmatizing
 Shortage of safe, effective treatments
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Resistance is a huge problem
Affected patients represent a low-priority
market for Western pharma manufactures.
Neglected Diseases

Where does ND research take place?

Universities!
 Department of Defense
 NIH/NIAID
 Research institutes
“30 billion dollars of total public spending (that includes
government spending for research in institutes, universities,
and government facilities), on health research worldwide,
only an estimated 100 million dollars was spent annually for
four of the most neglected diseases combined.”
Research and Access Gap
Pecoul, PLoS Med. 2004
Why?

Lack of market-based incentives for the
pharmaceutical industry
 The
pharmaceutical industry in the U.S.
derives only 5-7% of its profits from all LMI
countries
 Latin America, Africa, Asia (excluding Japan),
and Australia comprised only 12% of the total
worldwide market for pharmaceuticals,
including generic drugs
Other Issues
Heat-stable formulations
 Formulation for children
 Poor diagnostic
technology
 Lack of suitable drug
regiments

Malaria
$323 million (2004)
 49%: NIAID and the Gates Foundation

 Account
for 80% of growth in funding (’93-’04)
37%: Drugs
 24%: Vaccines
 <1%: Diagnostics
 “Were malaria research funded at the
average rate for all medical conditions,
it would receive more than $3 billion in
annual R&D funding.”
Malaria R&D Alliance
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African Trypanosomiasis
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“African Sleeping Sickness”
Between 300-500K deaths each
year in Africa
A local disease – prevalence as
high as 20-50% in some areas
Symptoms: pain, headaches in
first phase, severe neurological
disease (confusion, sleep cycle
disruption, etc.)
Fatal without treatment
African Trypanosomiasis

Case Study
 Well-studied
disease
~13,000 publications (PubMed)
 Caused by protozoan parasite

 Melarsoprol
– most widely-used
Developed in 1940’s
 Arsenic-based, administered by
injection (extremely painful)
 Fatal for about 10% of cases
 Drug resistance
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African Trypanosomiasis
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Case Study (con’t)
 Eflornithine
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“Resurrection drug”
Developed in 1970’s (Albert Sjoerdsmanot)
Approved by FDA in 1990; Aventis discontinued
production in 1995

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– effective, less toxic
Patent rights and remaining stocks of drug donated to
WHO (unsuccessfully tried to secure manufacturer)
New use for eflornithine discovered 5 years later and
was marketed as Vaniqa

Public-Private Partnership (PPP) formed: Brystol-Myers
Squibb, Dow Chemical Co, Akorn Manufacturing Inc,
Aventis, WHO, MSF
Case Study: Tuberculosis
(Also the neglected disease of the week!)
Mycobacterium Tuberculosis
 Still a major problem in the world

Dye, Christopher, “Global Epidemiology of Tuberculosis” The Lancet Vol. 367
Trajectories of
tuberculosis
epidemic for nine
epidemiologically
different regions
of the world.
Case Study: Tuberculosis
22 countries account for 80% cases of TB
Burden ranking
1. India
2. China
3. Indonesia
4. Nigeria
5. South Africa
6. Bangladesh
7. Pakistan
8. Ethiopia
9. Philippines
10. Kenya
11. Dem Rep of Congo
12. Russian Fed
13. Viet Nam
14. Tanzania
15. Uganda
16. Brazil
17. Afghanistan
18. Thailand
19. Mozambique
20. Zimbabwe
21. Myanmar
22. Cambodia
BCG Vaccination
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Bacillus Calmette-Guerin
 Albert
Calmette and Camille Geurin
 1921
 Live
vaccine from Mycobacterium bovis
 Variable effectiveness against pulmonary TB
70% protecting in UK study
 No protecting in India study
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Too late?
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Only have we recently in the past decade
or so realize that tuberculosis is a large
threat and a big problem in public health.
TB: MDR-TB
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Resistance to at least isoniazid and rifampicin
MDR-TB reveals problems infrastructure
 Misuse
of antibiotics
 Inadequate public health systems
 Poor quality “counterfeit” drugs
 Default on treatment

Challenges to treating MDR-TB
 Cost
up to 1,400x regular treatment (“second-line”)
 Up to 2 years of treatment
 No new drugs developed in the past 40 years
 HIV co-infection inc proportion of resistant cases
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425,000 cases of MDR-TB a year globally
TB: XDR-TB (extensive/extreme)
“Virtually untreatable” TB
 “MDR-TB plus resistance to (i) any
flouroquinolone, and (ii) at least 1 or 3
injectable second-line drugs capreomycin,
kanamycin, amikacin.
 Of 17,690 isolates of 49 countries (20002004), 20% were MDR-TB, and 2% were
XDR-TB
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XDR-TB
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Paul Sommerfield: “XDR-TB is very
serious—we are potentially getting close
to a bacteria that we have no tools, no
weapons against.”