1. MEETING THE
CHALLENGES FOR DRUG
DEVELOPMENT IN THE
21st CENTURY
Jan S. Rosenbaum, Ph.D.
CincyTech

2. Jan S. Rosenbaum, Ph.D.
Rosenbaum holds a Ph.D. in pharmaceutical chemistry from
the University of California at San Francisco and a
postdoctoral fellowship in clinical pharmacology from
Stanford University. She is the author of more than 50
original papers, short communications and abstracts in peer
reviewed journals and has been an invited speaker at
numerous international meetings.
She holds an adjunct professor appointment in the
Department of Pharmacology at The Ohio State University
where she lectures in Pharmacogenomics, and a Visiting
Scholar appointment in the Department of Pharmacology at
the University of Cincinnati, where she co-developed a
graduate course in New Drug Discovery-Preclinical
Development, for those individuals seeking to understand
process in the context of current global market forces and
Jan S. Rosenbaum, Ph.D., is a director of life sciences for CincyTech and founder
of BRK-1 Technical Advisors Inc. a pharmacology and technical due-diligence
consulting services practice supporting the pharmaceuticals and biotechnology
communities.
To learn more about Dr.
Rosenbaum, click here.
the drug development
opportunities.

3. Objectives
What has happened to the Pharma industry?
What is “Innovation” and where do we look for it?
What does it mean to be second to the market?
How does this affect me as a Pharmacologist?

4. Productivity in the last
60 yearsb
• Productivity has remained flat despite increased R&D spending
Source: a: B. Munos, Nat Rev Drug Disc 8:959-968 (2009)
b: KI Kaitin, Clin Pharmacol Ther 87(3): 356-361 (2010)

5. Can This Trend Continue?
Let’s examine the various pressures that
have converged on the Industry
R&D output/What happens as we hit the Patent Cliff?
The rising cost of healthcare in the US and world-wide
The US Regulatory environment

6. “Business as Usual” is No Longer an
Option for the Industry
The Patent Cliff is a problem
36 blockbuster drugs (annual sales > $1B) saw patents expire between
2009-2012
WW sales for these products exceed $112B
Third party payers are demanding demonstration of therapeutic
and/or economic advantages over ALL competitive products (including
non-therapeutic options)
This is increasingly challenging in the ex-US market
Improvement in safety profile is no longer sufficient to get on the market
The bar has been raised for Regulatory approval in the US
Greater focus on pre-approval safety as well as post-marketing surveillance in
the post-Vioxx era

7. What is Innovation?
Innovation means different things to
different people
Scientists
Patent attorneys
Consumers/Customers
Third Party Payers

8. Research vs. Innovation
 Research: Transforming knowledge into
information
 Innovation: Transforming knowledge into
products to create value for the consumer
 Medicinal Product Innovation: Chemistry
(structure/drug class), Method of Synthesis
(process), Formulation, PK/PD, Pharmacogenetic
 The Consumer: Patient, Physician, Third Party Payer
(health-care systems, government)

9. Innovation-Novelty
Novelty and “Newness” are distinct concepts
 “Newness” implies a new creation (i.e. a new
chemical entity)
 Novelty can be a NCE or it can be a new use for a
known compound, or a new
method, formulation, etc.
 From a patent standpoint, it must be something that is
“non-obvious” to someone skilled in the Art
 Novelty/Newness is a key
component of Innovation

10. Innovation-Usefulness
Unless an invention is useful, it is not innovative
Utility depends on the perspective of the user
Source: JK Aronson et. al. Nat Rev Drug Discovery 11:253-254 (2012)

11. What do Physicians
Consider Novel?
Survey of 184 expert physicians across 15
medical specialties and 30 US academic centers
Improved efficacy (55%)
Novel mechanism of action-first in class (37%)
Impact on practice in field (24%)
Less Important
Improved safety, ease of patient use, re-application
potential, scientific merit (7-15%)

12. Why Are There Me-Toos?
If you are working on a new MOA, someone else
is too
For new drug classes approved since 1990, >80% of
the follow-on drugs were in clinical trials before
approval of the first-in-class drug
For new drug classes where the first-in-class was
approved since 1990, >70% of the follow-on drugs
were in Phase II, and > 60% were in Phase III
Source: DiMasi JA and Faden LB Nat Rev Drug Disc 10:23-27 (2011)

13. Is It Important To Be
First-To-Market?
Source: Schultz U and Ringel M Nat Rev Drug Disc 12: 419-420 (2013)
Value

14. Source: Schultz U and Ringel M Nat Rev Drug Disc 12: 419-420 (2013)
Value How Quick To Market
Do You Have to Be?

15. Achieving Commercial
Success With a Me-Too
Differentiating characteristics in a subgroup of
patients-unique unmet need
Distinctive mechanistic class dynamics
Right drug for the right patient requires cycling
through multiple drugs with the same MOA
Sales force can drive market adoption

16. Why Do Drugs Fail?
Source: Khana I DDT 17: 1088-1102 (2012)
Commercial Failure = Strategic, lack of discrimination vs. competition,
efficacy & economic risk/benefit ratio

17. Where Do Drugs Fail?
 The majority of drugs fail in Phase II
Source: Khana I DDT 17: 1088-1102 (2012)

18. What is Pharma Doing?
M&A between major & mid-size Pharma was an
attempt to address the Patent Cliff issue
 Short-term “fix” that led to massive layoffs in the industry without
an increase in R&D efficiency
Pharma is looking to develop drugs for rare
diseases, on the assumption that the orphan drug
can be reapplied to the treatment of a more common
disease
Pharma is looking to Biotech and Academia to
provide a portion of their pipeline

19. The Orphan Drug Approach
 Requires disease pathology understanding
 Companion diagnostics to select patient populations and
streamline clinical trials
 Provides priority drug status and shorter timelines for
clinical development
 Has tax incentives for development
 Potential upside to capture multiple markets after
demonstration of safety & efficacy in initial orphan market

20. Increased Effort to Develop
Orphan Drugs
Source: FDA Law Blog Feb 13, 2013 http://www.fdalawblog.net/fda_law_blog_hyman_phelps/orphan-drugs/

21. Source: I. Melnikova, Nat Rev Drug Discovery 11: 267-268 (2012)
Where Are Orphan Drugs
Successful?

22. Developing New
Drugs/Targets
Everyone is a player at the Discovery Stage
Only Biotech/Pharma have the capacity to get to
NDA/BLA
Biotech continues to be the primary source for
development and marketing of biologics

23. Why Worry About
Cost?

24. Source: SM Paul et. al. Nat Rev Drug Disc 9:203-214 (2010)
Understanding the Cost of
Clinical Trials

25. •Approval phase is shorter for orphan drugs because of priority status
•For standard NMEs, Clinical phase and Approval phase length varies by therapeutic class
Source: KI Kaitin & JA DiMasi, Clin Pharmacol Ther 89 (2): 183- 188 (2011)
Not All Trials Are Created
Equal

26. Source: SM Paul
et. al. Nat Rev
Drug Disc 9:203-
214 (2010)
Move to the “Fail Fast” Model in
Clinical Trial Design

27. A New Model of
Pharmaceutical Innovation
Pharma simply cannot afford to do it alone!
Source: KI Kaitin, Clin Pharmacol Ther 87(3): 356-361 (2010)

28. Then vs. Now
Blockbuster Model
Large patient population with high sales potential
 Crowded markets, difficult to differentiate
 Difficult to demonstrate enhanced value
The evolving model
Targeted therapies for specialized markets
 Biomarkers & companion diagnostics inform clinical trial
design & streamline patient selection
 Pharmacoeconomic endpoints incorporated into trial
design
 Enhanced post-marketing surveillance
 Dependence on CROs

29. What Does This Mean For the
Discovery Pharmacologist?
• In order to be successful in today’s Pharmaceutical
marketplace, it is no longer sufficient to demonstrate a
drug is safe and effective
• The NME must also be offer significant economic and
therapeutic value
– Disruptive technology-only distinctive “me toos”
– The clinical trial setting and patient population must be
considered at target selection
– The Discovery program must be designed to meet both customer
(unmet medical) and third-party payer objectives
• If the drug does not add value, no one will reimburse it!

30. Pharmacologists are Ideally
Suited to Guide the Transition
 Rational target selection and target validation to meet the
unmet need
 Development of biomarkers and functional imaging tools
to assess efficacy and inform dose selection in
preclinical, proof-of-concept, and later-phase trials
 Development of modeling & simulation and resource-
sparing adaptive trial design strategies.

31. Are YOU Ready To Meet the
Challenges That The
Industry Faces?
For more about CincyTech visit our
website at www.cincytechusa.com