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Neglected Diseases and the Research Gap

Neglected Diseases and the Research Gap. UAEM Introductory Seminars. October 17, 2009. Canadian Patient: High Blood Pressure (Hypertension) Treatment Options 50+ Cost $20-100/year Availability High (need prescription) Side Effects

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Neglected Diseases and the Research Gap

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  1. Neglected Diseasesand the Research Gap UAEM Introductory Seminars October 17, 2009

  2. Canadian Patient: • High Blood Pressure (Hypertension) • Treatment Options • 50+ • Cost • $20-100/year • Availability • High (need prescription) • Side Effects • Low blood pressure (dizziness, lightheadedness, headache, change in vision, and fatigue)

  3. Alpha Blockers / Inhibitors Cardura (Doxazosin)Catapres (Clonidine)Dibenzyline (Phenoxybenzamine)Hytrin (Terazosin)Micardis (Telmisartan)Minipress, Minizide (Prazosin) Beta Blockers Blocadren, Timolide (Timolol)Cartrol (Carteolol)Cibenzyline (Phenoxybenzamine)Coreg (Carvedilol)Corgard, Corzide (Nadolol)Inderal, Inderide, Innopran (Propranolol)Kerlone (Betaxolol)Levatol (Penbutolol)Lopressor, Toprol (Metoprolol)Normodyne, Trandate (Labetalol)Sectral (Acebutolol)Tenormin, Tenoretic (Atenolol)Visken (Pindolol)Zebeta, Ziac (Bisoprolol) Calcium Channel Blockers Adalat, Procardia (Nifedipine)Caduet (Amlodipine Besylate + Atorvastatin Calcium)Cardizem, Dilacor, Tiazac (Diltiazem)Cardene (Nicardipine)Calan, Covera, Isoptin, Veralan, Tarka (Verapamil)DynaCirc (Isradipine)Norvasc, Lotrel (Amlodipine)Plendil, Lexxel (Felodipine)Posicor (Mibefradil)Sular (Nisoldipine) Angiotensin Converting Enzyme (ACE) Inhibitors Aceon (Perindopril Erbumine)Accupril (Quinapril)Altace (Ramipril)Capoten, Capozide (Captopril)Lotensin (Benazepril)Mavik (Trandolapril)Monopril (Fosinopril)Prinivil, Prinzide, Zestril, Zestoretic (Lisinopril)Univasc, Unitrec (Moexipril)Vasotec, Vaseretic (Enalapril) Angiotensin II Receptor Antagonists Atacand (Candesartan)Avapro, Avalide (Irbesartan)Benicar (Olmesartan Medoxomil)Benicar HCT (Olmesartan Medoxomil + Hydrochlorothiazide)Cozaar, Hyzaar (Losartan)Diovan (Valsartan)Micardis (Telmisartan) Diuretics Aldactone, Aldactazide (Spironolactone)Bumex (Bumetanide)Camadex, Demadex (Torsemide)Diuril, Hydrochlorothiazide, HCTZ, Hydrodiuril, Oretic, Enduron (Thiazides)Dyazide, Maxzide, Moduretic (Combinations)Dyrenium (Triamterene)Lasix (Furosemide)Lozol (Indapamide)Mykrox (Metolazone)Zaroxolyn, Mykrox (Metolazone) More than 50!!!

  4. South Asian Patient: • Leishmaniasis • Treatment Options • 5 • Cost • $50-500/treatment of 20-30 days • Side Effects • Toxicities to major organs (renal, hepatic, cardiac, pancreatic) • GI problems, fever, fatigue, rash, hypo/hypertension, Diabetes Mellitus • Availability • Due to limited health care access and funding

  5. Paromomycin Interferon-gamma-1b Only 5!!! Pentamidine Sodium antimony gluconate Amphotericin B

  6. Question: Why is the treatment so different for these two diseases? Answer: It’s all about the pipeline… the drug pipeline

  7. 1. Discovery: - basic research - discover therapeutic targets - possible candidate molecules 2. Development: - formulation - assessment via clinical trial($$$) - mass production processes 3. Delivery: - registration - manufacturing - sale - distribution Time: 8 - 15 years Cost: $200 million - $1 billion Pecoul, PLoS Med. 2004

  8. Discovery: - Produces useful knowledge, but not marketable technologies - Requires creativity and relatively modest investment - Carried out by academic researchers with grants from governments/charities 2. Development: - Produces marketable technologies - Requires big investments: testing is expensive and most candidates will fail - Carried out by private biotech and pharmaceutical industries who expect to make a profit 3. Delivery: • - Requires infrastructure • Relatively inexpensive compared to drug development • Problems with intellectual property (patents) • - Also carried out by mainly by industry, for profit

  9. Cancer Cardiovascular disease HIV/AIDS TB Malaria Tropical diseases

  10. Cancer Cardiovascular disease HIV/AIDS TB Malaria Tropical diseases

  11. Advocacy groups/charities Industry Government Patients

  12. Advocacy groups/charities Industry Government Patients

  13. 10/90 Gap • 10% of Total funding for R&D • Poorest 90% of the world’s population’s health problems • Needs present – but no resources available • Disconnect with needs and invested interest What former MSF-USA director Nicolas De Torrente called "a fundamental mismatch, expressed as millions of lives lost each year, between human needs and scientific innovation."

  14. Neglected Diseases • Limited or no basic health care • Life-long disabilities • Many cause mortality • Economic and social costs • A neglected disease… • Predominantly affects people who are too poor to constitute a market attractive to R&D investment

  15. Malaria Major health burden: 250,000,000 cases and 900,000 deaths/year, mostly children Major economic burden: reduced African GNP by 50% from 1965 to 1990

  16. Malaria Present in more than 100 countries and threatens half of the world’s population Widespread resistance to old treatments Only one major new class of drugs in last decade (artemisinin derivatives) Difficult to synthesize; frequent shortages No vaccine

  17. Malaria

  18. Tuberculosis 2,000,000,000 people (1 in 3 worldwide) are currently infected – mostly dormant #1 killer of HIV/AIDS patients worldwide Curative therapy requires months or years to complete Drug resistance is a major problem XDR-TB: virtually untreatable

  19. Tuberculosis

  20. A major parasitic killer on a worldwide scale Superficial infections cause disfiguring skin lesions, and destroy the mouth and nose (non-fatal), visceral infections damage organs and bone (fatal) Once clinical symptoms show, fatal within months if untreated Leishmaniasis TDR Poster 2001

  21. Leishmaniasis Spread and fatality are correlated to environmental conditions, malnutrition, complex emergencies and large population movements Treatments are limited by the same factors, in addition: Difficult administration (IV, IM ) Lengthy treatment time (20-30d) Toxicity (cardiac, pancreatic, nephritic, hepatic, otic, GI, teratogenicity) Cost Resistance

  22. Leishmaniasis

  23. Onchocerciasisriver blindness Parasitic worm Onchocerca volvulus invades the skin and eyes, causes lifelong blindness and lesions Affects the most fertile agricultural areas in tropical Africa

  24. Onchocerciasisriver blindness Only one treatment (ivermectin) Not curative, but controls the symptoms of infection and suppresses its spread A single dose every 6-12 months until asymptomatic Manufacturer donates it for free and onchocerciasis has been eliminated from several African countries However, resistance is beginning to emerge

  25. Onchocerciasisriver blindness

  26. The neglected diseases The “big three”: HIV/AIDS Malaria Tuberculosis “Most neglected” diseases: Dengue fever Leishmaniasis Schistosomiasis African trypanosomiasis Chagas disease Trachoma Buruli ulcer Leprosy Yaws Lymphatic filariasis Onchocerciasis >6 million deaths annually10% of global disease burden 1 billion currently infected10% of global disease burden

  27. Neglected needs Diagnostic tests Need for simple, easy to administer tests in areas with limited health care facilities Different populations Need for pediatric formulations of drugs Different settings Need for portability and heat-stability

  28. thank you!info@ubc-uaem.org

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