DIA EURO 2005 Childh Dis Dev Countr Klaus Rose

7/29/2019 DIA EURO 2005 Childh Dis Dev Countr Klaus Rose

1/25

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

klaus.rose@pharma.novartis.com


2/25


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


3/25


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


4/25


Expectations Before & After The 1990ies


5/25


(Reference 26)

Global Distribution Of Child Mortality


6/25


Children And Access to Medical Treatment


7/25Klaus Rose DIA EuroMeeting Lisboa 2005 Track 12 Session 1 - 7 -

Frequent Childhood Diseases In The

Developing World

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

Diarrhea

Malaria

Schistosomiasis

Vitamin A deficiency



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



Frequent Childhood Diseases In Developing

Countries (2)

Onchocerciasis

Leprosy

Lymphatic Filariasis

Guinea Worm

Blinding Trachoma

African Trypanosomiasis



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



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



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



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



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



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



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.


17/25


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


18/25


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


19/25


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


20/25


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


21/25


Thank you!


22/25


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


23/25


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


24/25


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


25/25

Kl R DIA E M ti Li b 2005 T k 12 S i 1 25

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

DIA EURO 2005 Childh Dis Dev Countr Klaus Rose

Documents

BEST FEATURE DOCUMENTARY...

Methylmalonic Aciduria · Arch. Dis. Childh., 1967, 42,...

Klaus Rith

PAÍS / COUNTR ORGANIZACIÓN / ENTIDADE / ORGANIZATION Y …

GEF-SGP Countr y Progr amme Strategy for utilization of ...

Klaus Bierschenk E65 Bus-Systeme. Klaus Bierschenk...

Countr i -...

Klaus Graf

Casino all in one Combined kiosk solution for automated...

y Track & Field Cross Countr - MIT

Klaus Peter Flaschel - Schriftenverzeichnis Klaus Peter ...

Hypoglycemia in the infant and childh. It is a medical...