Post on 27-Dec-2015
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) Operational Definition (FDA: U.S. Orphan
Drug Act, 1983) Any disease that:
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)
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
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.”
Why?
Lack of market-based incentives for the pharmaceutical industryThe 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
African Trypanosomiasis
“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
African Trypanosomiasis Case Study (con’t)
Eflornithine – effective, less toxic “Resurrection drug” Developed in 1970’s (Albert Sjoerdsmanot) Approved by FDA in 1990; Aventis discontinued
production in 1995 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
Mycobacterium Tuberculosis Still a major problem in the world
(Also the neglected disease of the week!)
Case Study: Tuberculosis22 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 Fed13. Viet Nam 14. Tanzania 15. Uganda 16. Brazil 17. Afghanistan 18. Thailand 19. Mozambique 20. Zimbabwe 21. Myanmar 22. Cambodia
BCG Vaccination Bacillus Calmette-Guerin
Albert Calmette and Camille Geurin1921Live vaccine from Mycobacterium bovisVariable effectiveness against pulmonary TB
70% protecting in UK study No protecting in India study
Too late? 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 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
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 (2000-2004), 20% were MDR-TB, and 2% were XDR-TB