MEETING THE CHALLENGES FOR
DRUG DEVELOPMENT IN THE 21st CENTURY
Jan S. Rosenbaum, Ph.D.CincyTech
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.
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?
Productivity in the last 60 years
b
• 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)
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
“Business as Usual” is No Longer an Option for the Industry
The Patent Cliff is a problem36 blockbuster drugs (annual sales > $1B) saw patents expire
between 2009-2012WW 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 USGreater focus on pre-approval safety as well as post-marketing
surveillance in the post-Vioxx era
What is Innovation?
Innovation means different things to different people
Scientists
Patent attorneys
Consumers/Customers
Third Party Payers
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)
Innovation-NoveltyNovelty 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
Innovation-UsefulnessUnless an invention is useful, it is not innovative
Utility depends on the perspective of the userSource: JK Aronson et. al. Nat Rev Drug Discovery 11:253-254 (2012)
What do Physicians Consider Novel?
Survey of 184 expert physicians across 15 medical specialties and 30 US academic centersImproved efficacy (55%)Novel mechanism of action-first in class (37%)Impact on practice in field (24%)Less ImportantImproved safety, ease of patient use, re-
application potential, scientific merit (7-15%)
Why Are There Me-Toos?
If you are working on a new MOA, someone else is tooFor 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)
Is It Important To Be
First-To-Market?
Source: Schultz U and Ringel M Nat Rev Drug Disc 12: 419-420 (2013)
Va
lue
Source: Schultz U and Ringel M Nat Rev Drug Disc 12: 419-420 (2013)
Va
lue
How Quick To Market Do You Have to Be?
Achieving Commercial Success With a Me-Too
Differentiating characteristics in a subgroup of patients-unique unmet need
Distinctive mechanistic class dynamicsRight drug for the right patient requires
cycling through multiple drugs with the same MOA
Sales force can drive market adoption
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
Where Do Drugs Fail?
The majority of drugs fail in Phase II
Source: Khana I DDT 17: 1088-1102 (2012)
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 efficiencyPharma 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
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
Increased Effort to Develop Orphan Drugs
Source: FDA Law Blog Feb 13, 2013 http://www.fdalawblog.net/fda_law_blog_hyman_phelps/orphan-drugs/
Source: I. Melnikova, Nat Rev Drug Discovery 11: 267-268 (2012)
Where Are Orphan Drugs Successful?
Developing New
Drugs/Targets
Everyone is a player at the Discovery Stage
Only Biotech/Pharma have the capacity to get to NDA/BLABiotech continues to be the primary
source for development and marketing of biologics
Why Worry About Cost?
Source: SM Paul et. al. Nat Rev Drug Disc 9:203-214 (2010)
Understanding the Cost of Clinical Trials
• Approval phase is shorter for orphan drugs because of priority status• For standard NMEs, Clinical phase and Approval phase length varies by therapeutic classSource: KI Kaitin & JA DiMasi, Clin Pharmacol Ther 89 (2): 183- 188 (2011)
Not All Trials Are Created Equal
Source: SM Paul et. al. Nat Rev Drug Disc 9:203-214 (2010)
Move to the “Fail Fast” Model in Clinical Trial
Design
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)
Then vs. NowBlockbuster Model
Large patient population with high sales potential Crowded markets, difficult to differentiate Difficult to demonstrate enhanced value
The evolving modelTargeted 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
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!
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.
Are YOU Ready To Meet the Challenges That The Industry Faces?
For more about CincyTech visit our website at www.cincytechusa.com
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