Gaining Consensus On Emerging Science:The ADME Panel As An Exemplar

24 Pages·2009·1.31 MB·English

Gaining Consensus On Emerging
Science:The ADME Panel As An Exemplar
Beena Koshy, Ph.D.
EMEA-EFPIA Workshop
December 19th, 2008
Outline
Introduction
– Need for an ADME panel in drug development
Challenges in developing a panel
– Organizational
– Scientific
Innovation is Powered by Collaboration
ADME Panel Development
– Development of a Consensus List of ADME Genes and
Genetic Markers
– Characterization & Compilation of an ADME List
– Criteria & Selection of Genetic Variants
Summary
Need for ADME Panel in Drug
Development
40% of the Failure in
Drug Development is
Attributed to PK
Issues
Nature Reviews, Drug Discovery, March 2003
Regulatory Impetus
FDA's Critical Path Initiative
EMEA Road Map to 2010
"There are currently significant needs, but also significant
opportunities for developing tools that can more reliably and
more efficiently determine the safety of a new medical product"
FDA White Paper, 16 March 2004
Challenges in Developing a Consensus
ADME Panel
Organizational Challenge
– A number of pharma working together
Scientific Challenges
– Determine which genes have enough
evidence to justify testing on a routine
basis, and which variations should be
measured in these genes
DDeevveellooppmmeenntt ooff aa PPhhaarrmmaa
CCoonnsseennssuuss AADDMMEE PPaanneell
AADDMMEE PPaanneell WWoorrkkiinngg GGrroouupp
Innovation is powered by collaboration!
PPhhaarrmmaacceeuuttiiccaall CCoommppaanniieess
AAccaaddeemmiicc CCeenntteerr
Genome Quebec & Montreal Heart Institute
Pharmacogenomics Centre
GGeennoottyyppiinngg BBiiootteecchh CCoommppaanniieess
Gene Selection of ADME Panel
CCoollllaattiioonn ooff ggeennee lliissttss
Class No of %
ssuubbmmiitttteedd bbyy ppaarrttiicciippaannttss
Genes
~~333322 ggeenneess SSuubbmmiitttteedd
Phase 1 126 43
DDrruugg mmeettaabboolliissmm
–– pphhaassee II
Phase 2 68 23
–– pphhaassee IIII
–– ttrraannssppoorrtteerrss
DDrruugg TTaarrggeettss
Transporters 77 26
CChhaannnneellss
AADDMMEE mmoodduullaattoorrss Modifiers 24 8
–– NNuucclleeaarr
RReecceeppttoorrss ((PPXXRR))
Genes Submitted By Pharma Companies
Total Number of Genes Submitted
d 350
e
t
t
i 300
m
b
u 250
S

s
200
e
n
e
150
G

f
o
100

o
N
50
0
Companies submitting data
Genes Submitted
Total 1 2 3 4 5 6 7 8 9
Companies 1-9
DDeeffiinniinngg tthhee AADDMMEE ““CCoorree LLiisstt””
Gene Selection Process
IInncclluussiioonn CCrriitteerriiaa
GGeenneess ddeeeemmeedd ttoo bbee ddiirreeccttllyy iinnvvoollvveedd iinn ddrruugg mmeettaabboolliissmm
aanndd//oorr hhaavvee tthhee aabbiilliittyy ttoo iinnfflluueennccee aa ddrruugg’’ss
pphhaarrmmaaccookkiinneettiicc pprrooffiillee
IIddeennttiiffiieedd bbyy FFDDAA aass aa vvaalliiddaatteedd bbiioommaarrkkeerr
SSuuppppoorrtteedd bbyy ppuubblliisshheedd lliitteerraattuurree ooff mmoorree tthhaann oonnee ggrroouupp
tthhaatt tthhee vvaarriiaattiioonn aalltteerrss ggeennee ffuunnccttiioonn
SSuuppppoorrtt bbyy KKOOLLss ((PPhhaarrmmaa DDMMEETT ggrroouuppss)) iinn ddrruugg
mmeettaabboolliissmm ffiieelldd aass hhaavviinngg aalltteerreedd pprrootteeiinn ffuunnccttiioonn