Challenges for drug development jsr slides aug 2013


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Challenges for drug development jsr slides aug 2013

  2. 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. 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. 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. 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. 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. 7. What is Innovation? Innovation means different things to different people Scientists Patent attorneys Consumers/Customers Third Party Payers
  8. 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. 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. 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. 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. 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. 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. 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. 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. 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. 17. Where Do Drugs Fail?  The majority of drugs fail in Phase II Source: Khana I DDT 17: 1088-1102 (2012)
  18. 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. 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. 20. Increased Effort to Develop Orphan Drugs Source: FDA Law Blog Feb 13, 2013
  21. 21. Source: I. Melnikova, Nat Rev Drug Discovery 11: 267-268 (2012) Where Are Orphan Drugs Successful?
  22. 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. 23. Why Worry About Cost?
  24. 24. Source: SM Paul et. al. Nat Rev Drug Disc 9:203-214 (2010) Understanding the Cost of Clinical Trials
  25. 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. 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. 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. 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. 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. 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. 31. Are YOU Ready To Meet the Challenges That The Industry Faces? For more about CincyTech visit our website at