Research Gap and Neglected Diseases Edith Han February 8, 2007 Access to Essential Medicines (UAEM)

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) 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)

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.”

Research and Access Gap

Pecoul, PLoS Med. 2004

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!)

Dye, Christopher, “Global Epidemiology of Tuberculosis” The Lancet Vol. 367

Trajectories of tuberculosis

epidemic for nine epidemiologically different regions

of the world.

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

XDR-TB Paul Sommerfield: “XDR-TB is very

serious—we are potentially getting close to a bacteria that we have no tools, no weapons against.”