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DIA EURO 2005 Childh Dis Dev Countr Klaus Rose

Apr 04, 2018

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    Klaus Rose DIA EuroMeeting Lisboa 2005 Track 12 Session 1 - 1 -

    DIA EuroMeeting Lisbon 2005

    Track 12, Session 1

    Pharmaceutical Research Infrastructure

    and Developing Countries: Potential forResearch into Childhood Diseases

    Klaus Rose, Novartis Pharma, Basel, Switzerland

    [email protected]

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    Therapeutic Orphans

    Term coined by Henry Shearky in the USA 1963 todescribe position of children in pharmacotherapy

    Pediatric disclaimers: drug not tested in children

    Resulted in exclusion from therapeutic benefit ofefficacious medications, or off-label use

    A change started 1997 in the USA & is now expanding

    Today pharmaceutical industry is recognized as the

    motor of pharmaceutical innovation

    Its position in society is changing Societal expectations towards pharma are changing

    Paradigm: neglected diseases in developing countries

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    Children & Medicine World Bank Target

    5: Reduce by2/3 1990 - 2015 the under-

    five mortality rate26

    Infant deaths are most often the result of unhealthy conditionsaround the time of birth. Pneumonia, diarrhea, malaria, or measlesfrequently kill young children, especially those suffering fromchronic malnutrition. 26

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    Expectations Before & After The 1990ies

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    (Reference 26)

    Global Distribution Of Child Mortality

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    Children And Access to Medical Treatment

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    Frequent Childhood Diseases In The

    Developing World

    Viral infections (mumps, measles, rubella, varicella,pertussis, others)

    Diarrhea

    Malaria

    Schistosomiasis

    Vitamin A deficiency

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    Existing Treatments

    Viral infections: vaccines

    Bacterial infections: antibiotics

    Diarrhea: Oral rehydration therapy

    Malaria: Co-artem

    Schistosomiasis: chemotherapy (Praziquantel)

    Vitamin A deficiency: Vitamin A as food supplement

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    Frequent Childhood Diseases In Developing

    Countries (2)

    Onchocerciasis

    Leprosy

    Lymphatic Filariasis

    Guinea Worm

    Blinding Trachoma

    African Trypanosomiasis

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    Treatment For Group 2

    Onchocerciasis: Ivermectin

    Leprosy: Multi-Drug Therapy (MTD): dapsone,rifampicin (Rimactane), clofazimine (Lamprene),

    Lymphatic Filariasis: Albendazole & Ivermectin Guinea Worm: Tylenol

    Blinding Trachoma: Zithromax

    African Trypanosomiasis: Triple therapy

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    Treatment Programs Group 2 Diseases 2004

    Disease Program & Donating Company Achievements

    Onchocerciasis Merck: ivermectin until now > 1bio tablets, > 300 mio treatments Over 25 years 11 mio childrenprotected, ~1 mio saved fromblindness

    Lymphatic Filariasis GlaxoSmithKline: albendazole(250 mio treatments to date),Merck: ivermectin (20 miotreatments to date)

    80 mio people in 37 countriesreceived treatment (2000: 3 miopeople at risk were covered)

    Guinea Worm Johnson & Johnson: tylenol for >3000 villages

    Disease affected dropped from10-15 mio in the 1980ies to 32000in 2003

    Blinding Trachoma Pfizer: > $130 mio zithromax &health education grants

    > 5 mio people healed of activeinfection; > 70000 cases of

    blindness prevented by surgery

    AfricanTrypanosomiasis

    Aventis: 1.2 mio ampoules tripletherapy, mobile medical teams,research on new formulation

    > 60000 people received medicalcounsel, screening, & treatment

    Leprosy Novartis: $35 mio in tripletherapy, eradicates with WHO

    >13 mio people cured, drop inprevalence > 90% since 1985.Endemic countries: 122 15

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    Case study 1: Leprosy

    Chronic infection by Mycobacterium leprae

    Long-term infection results in nerve damage and

    mutilation

    Has affected mankind since thousands of years

    Patients were regarded as contagious and were

    excluded from society

    Treatment is possible with Multi-Drug Therapy (MTD)

    Number of patients has dropped from > 15 Mio patientsto 500000 over the last 2 decades

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    Leprosy: Three Key Success

    Factors

    Availability of an effective therapy, provided free ofcharge to all patients in the world

    Highly successful de-stigmatization campaigns changing

    the image of leprosy to a normal, curable disease.

    A highly successful public-private collaboration between

    the governments of the affected countries, the WHO,

    non-governmental organizations and pharmaceutical

    industry

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    Case study 2: Trachoma*

    Trachoma is an easily spread infection of the eye.Repeated occurrences scar the upper eyelid, eventually

    turning it inward. The eyelashes then scratch the cornea,

    leading to blindness. It is a gradual yet painful condition

    affecting the poorest of the poor. Though it has blinded about eight million people

    worldwide, trachoma can now be controlled with a

    strategy called SAFE that combines treatment with

    prevention. TheInternational Trachoma Initiative

    (ITI)is dedicated to eliminate blinding trachoma by 2020.

    *www.trachoma.org

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    ITI (International Trachoma Initiative) SAFE Strategy

    Surgery to correct advanced stages of the disease

    Antibiotics to treat active infection: Zithromaxdonated by Pfizer

    Face washing to reduce disease transmission Environmental change to increase access to clean

    water and improved sanitation to eliminate disease

    altogether

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    ITI (International Trachoma Initiative)

    Collaborates with international agencies andgovernmental and nongovernmental organizations.

    Supports the World Health Organizations Alliance

    for Global Elimination of Trachoma by 2020 and the

    International Agency for Prevention of Blindnessglobal program Vision 2020: The Right to Sight.

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    Case study 3: Malaria and Tuberculosis

    Have led to two public-private partnerships to develop new

    needed medicines

    Medicines for Malaria Venture (MMV, www.mmv.org): A

    nonprofit organization created to discover, develop and

    deliver new affordable antimalarial drugs through effective

    public-private partnerships

    Global Alliance for TB Drug Development (TB Alliance,

    www.tballiance.org)

    The Global Alliance for TB Drug Development accelerates

    the discovery and development of faster-acting and

    affordable drugs to fight tuberculosis, a disease now

    infecting one in three people worldwide

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    New Research and Discovery Centers

    for Neglected Diseases

    AstraZeneca Bangalore Research Institute

    http://www.astrazeneca.com/communityproject/67.aspx

    Novartis Institute for Tropical Diaseses (NITD)www.nitd.novartis.com

    GlaxoSmithKline Tres Cantos Centre for Diseases of the

    Developing World Drug Discovery

    science.gsk.com/about/disease.htm

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    Remaining Gaps

    Need for new targets and compounds

    Better evaluation of safety & efficacy

    Clinical trials capacity in developing countries

    Uptake of new medicines into developing countrieshealthcare systems

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    Conclusions

    Excessive disease burdens continue to affect children and

    adults in the least developed countries, despite theexistence of effective treatments

    There are examples of successful interventions for several

    severe diseases

    More research is needed

    A new wave of initiatives and activities is emerging that

    focus on new drug discovery and development for

    neglected diseases

    Critical gaps remain. Involvement of all stakeholders to

    remove financial, scientific, regulatory and organisational

    barriers is necessary

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    Thank you!

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    References

    1. American Pediatric Pharmacology Research Unit Network (PPRU)

    www.ppru.org

    2. Americal Academy of Pediatrics, Committee on drugs: Guidelines for theethical conduct of studies to evaluate drugs in pediatric populations.

    PEDIATRICS 95; 1995: 286-294

    3. American Academy of Pediatrics, Committee on Drugs: Unapproved uses of

    approved drugs: the physician, the package insert, and the FDA. PEDIATRICS

    98; 1996: 143-145

    4. Choonara I et al.: Paediatric Medicines: global development and clinicalinvestigations. Scrip Report, PJB Publications Ltd, 2000

    5. Conroy S et al: Unlicensed and off label drug use in neonates. Arch Dis

    Childhood: Fetal & Neonatal Edition, 1999, 80, F142-145

    6. Conroy S et al: Survey of unlicensed and off label drug use in paediatric wards

    in European countries. BMJ 2000, 320, 79-82

    7. Conroy S et al: Unlicensed and off label drug use in acute lymphoblastic

    leukaemia and other malignancies in children. Ann Oncol 2003, 14, 42-47

    8 .Declaration of Helsinki http://www.wma.net

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    References (contd)9. EFPIA www.efpia.org

    10. EMEA Clinical Investigation of Medicinal Products in Children

    (CPMP/EWP/462/95)1997

    http://www.emea.eu.int/pdfs/human/ewp/046295en.pdf11. EMEA: ICH E11 as edited by EMEA

    http://www.emea.eu.int/pdfs/human/ich/271199EN.pdf

    12. FDA pediatric website: http://www.fda.gov/cder/pediatric/index.htm

    13. Impicciatore & Choonara: Status of new medicines approved by the

    European Medicine Evaluation Agency regarding paediatric use. British Journal

    of Clinical Pharmacology 1999; 49; 93-9714. Conroy S et al.: Unlicensesd and off label drug use in neonates. Arch Dis

    Child Fetal Neonatal Ed 1999, 80; F142-F145

    15. Gloeckler Ries LA: Childhood cancer mortality.

    http://seer.cancer.gov/publications/childhood/mortality.pdf

    16. McIntyre J et al.: Unlicensed and off label prescribing of drugs in general

    practice. Arch Dis Child 2000;83: 498-50117. Mller TR et al: Decreasing late mortality among five-year survivors of cancer

    in childhood and adolescence. Journal of Clinical Oncology 2001, 19, 3173-3181

    18. Parke TJ et al.: Metabolic acidosis and fatal myocardial failure after propofol

    infusion in children: five case reports. BMJ 1992, 305, 613-616

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    References (contd)

    19. Royal College of Paediatrics and Child Health: Ethics Advisory Committee:

    Guidelines for the ethical conduct of medical research involving children. Arch

    Dis Child 2000; 82: 177-18220. Smith K: Registering paediatric medicines in Australia. The Regulatory Affairs

    J 1998, 9, 304-308.

    21. Stephenson T: Medicines for children-the last century and the next. Arch Dis

    Child 2001, 85, 177-79

    22. Schaad UB: Drug therapy in children: still more art than science. Curr Opin

    Infect Dis 2001;14:301-2

    23. Taussig HB: A study of the German outbreak of phocomelia. JAMA 1962,

    180, 1106-1114

    24. Turner S et al: Unlicensed and off label drug use in paediatric wards:. BMJ

    1998; 316; 343-345

    25. WHO Information Fact Sheer no. 178 (1998): Reducing mortality from majorkillers of children. http://www.who.int/inf-fs/en/fact178.html

    26. World bank millennium development goals: Reduce child mortality.

    http://www.developmentgoals.org/Child_Mortality.htm

    27. Wax P: Elixirs, Diluents, and the Passage of the 1938 Federal Food, drug

    and Cosmetic Act. Ann Intern Med 1995;122; 456-461

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    References (contd)

    28. Wilson JT: An update on the therapeutic orphan. PEDIATRICS 104; 1999:

    585-590

    29. Kleist P: Pediatric drug development. Applied Clinical Trials January 2002,40-48

    30. Rose K: Pediatric Drug Development: Implementation of pediatric aspects

    into the general drug development process. Applied Clinical Trials 2005; 14 (1),

    50-52 http://www.actmagazine.com/appliedclinicaltrials/article/articleDetail.jsp?id=140819

    31. www.who.int/lep

    32. Research and Development for Neglected Diseases. International Federation

    of Pharmaceutical Manufacturers Associations (IFPMA), October 2004