Biology Reference
In-Depth Information
CHAPTER
1
Application of Translational
Science to Clinical
Development
Koustubh Ranade
1
, Brandon W. Higgs
1
, Ruth
March
2
, Lorin Roskos
1
, Bahija Jallal
1
, Yihong Yao
1
1
MedImmune, LLC, Gaithersburg, Maryland
2
AstraZeneca Pharmaceuticals, Research and Development Genetics
Department, Mereside, Macclesfield, Cheshire, United Kingdom
1.1 INTRODUCTION
The pharmaceutical industry is in crisis. In the year 2012 alone, branded drugs valued at
over $30 billion lost patent protection, thereby allowing generic manufacturers to make and
sell lower-priced versions of blockbuster drugs
[1]
. The industry as a whole has been unsuc-
cessful in replacing drugs going off-patent with sufficient new molecular entities (NMEs).
Despite staggering investment in R&D - the top ten pharmas spent $60 billion on R&D in
2010 - the number of approvals has changed little over the past decade (
Fig. 1.1
).
This level of investment without commensurate improvement in approvals of new medi-
cines is likely unsustainable and has, in fact, contributed to waves of mergers in the phar-
maceutical industry accompanied by tens of thousands of layoffs in 2007-2012.
Many reasons have been attributed to the lack of apparent productivity in big pharma, but,
as the graph in
Fig. 1.2
indicates, it is likely that the main culprit is the low probability of suc-
cess (PoS), perhaps as low as 10%, of investigational drugs entering Phase II clinical trials that
are eventually approved
[3]
. Coupled with the high cost of clinical trials, this low PoS makes
drug development a highly risky proposition, and drives the industry to invest in already val-
idated targets that are more likely to yield approvable, albeit less innovative, drugs, at the end
of a multi-year effort.
