De Geneesmiddelenpijplijn
Prof. Dr. Gert Folkerts
Division of Pharmacology,Utrecht Institut Pharmaceutical of Science
Faculty of Science, Utrecht University, The Netherlands
So, there are 3 main questions
to make the decission to develop a new drug
1) Should we do it? (strategic issues)
2) Could we do it? (scientific and
technical issues)
3) Can we do it?
(operational issues)
Drug Discovery and Development
Edited by H.P. Rang. Publisher: Churchill Livingstone/Elsevier
Three main phases of creating a new drug
1) Discovery
2) Development
3) Commercialization
Drug Discovery and Development
Edited by H.P. Rang. Publisher: Churchill Livingstone/Elsevier
Tijd en kosten voor ontwikkeling
Drug Discovery and Development
Edited by H.P. Rang. Publisher: Churchill Livingstone/Elsevier
Drug Discovery and Development
Edited by H.P. Rang. Publisher: Churchill Livingstone/Elsevier
General overview of drug testing
From. Rang, Pharmacology
Safety
Future lead discovery will be
information driven
Drug Discovery and Development
Edited by H.P. Rang. Publisher: Churchill Livingstone/Elsevier
Biopharmaceuticals
Low-molecular-weight drug
Classical medicinal pharmaceutical product
Generic drug
Chemical and therapeutic equivalent of low-molecular-weight drug with
expired patent
Biopharmaceutical
“A medicinal product developed by means of one or more of the following
biotechnology practices: rDNA, controlled gene expression, antibody
methods”1
Biosimilar, or similar biological medicinal product
“A biological medicinal product referring to an existing one and submitted to
regulatory authorities for marketing authorization by an independent
applicant after the time the original product expired”1
Crommelin DJA, et al. Int J Pharm 2003;266:3-16.
LMW drugs vs biopharmaceuticals
Acetominophen =
Paracetamol Mw 150
Monoclonal
antibody:
Mw 150,000
Biopharmaceuticals have the highest
growth rate > US$ 92 billion in 2011
Knaeplein, 2007
Most biopharmaceutical
proteins have small
markets, but high value
< 10 kg/yr, > US$10,000/g
Gene Therapy: viruses as delivery system…
Stem cell therapy….
Adult stem cells
Embryonic stem cells
Most drugs drop out! 92 out of 100
Drug Discovery and Development
Edited by H.P. Rang. Publisher: Churchill Livingstone/Elsevier
30 % is niet werkzaam !
Nature Reviews, Drug Discovery
2004, 3, 711-719
Hart/bloedvaten vs Kanker 20% vs 5%
Nature Reviews, Drug Discovery
2004, 3, 711-719
Translational Medicine
What is next?
Finding diseases with functional genomics
Drug Discovery and Development
Edited by H.P. Rang. Publisher: Churchill Livingstone/Elsevier
Personalized Medicine
Reasons why drugs drop out
Drug Discovery and Development
Edited by H.P. Rang. Publisher: Churchill Livingstone/Elsevier
Creteria for project selection
r project selection.
Drug Discovery and Development
Edited by H.P. Rang. Publisher: Churchill Livingstone/Elsevier
What are the human targets?
Drug Discovery and Development
Edited by H.P. Rang. Publisher: Churchill Livingstone/Elsevier
High troughput screening
In 1907, Paul Ehrlich tested
605 compounds and finally
identified number 606,
salvasar,
(Diaminodioxyarsenobenzene) which was
brought on the market by
Hoechst for syphilis and
hailed as a miracle drug.
Drug Discovery and Development
Edited by H.P. Rang. Publisher: Churchill Livingstone/Elsevier
In Vivo Farmacologie
How and where biopharmaceuticals differ
from low molecular weight drugs?
• Molecular weight
• Complexity of structure
• Characterization
– Structure and physico-chemical properties
– Protein purity
– Biological activity
• Stability
• Immunogenicity
• Next generations….
• Delivery: Needle focused
Crommelin DJA, et al. Int J Pharm 2003;266:3-16.
Drug Discovery and Development
Edited by H.P. Rang. Publisher: Churchill Livingstone/Elsevier