Pain and Industry: Challenges for Drug Development and Marketing Douglas Y. Shapiro, MD, PhD Pfizer Global Research and Development, Ann Arbor, MI Symposium on Chronic Pain Treatment, University of Michigan, 25 May 2006

1 –2 Products Products High Risk Process years High Risk Process years Timelines for standard drug developmentDiscovery Exploratory Development Idea Drug Years Full Development Phase I Phase IIPhase III Preclinical Pharmacology Preclinical Safety Millions of Compounds Screened Clinical Pharmacology & Safety

Ways to shorten drug development New use for approved drug (eg Neurontin for PHN) –High probability of success, relatively fast development time NCE with precedented mechanism of action (eg Lyrica) –Moderately high probability of success, longer development time –Benefits Improvements over earlier compounds in PK/PD, regimen, safety, efficacy Maintains franchise beyond initially marketed drug Converting an unwanted side-effect into an indication –Challenges to third-party payers

More ways to shorten drug development NCE with unprecedented mechanism of action –Compound from in-licensing Excellent source of new ideas Shortens development time –Compound from internal source Lower probability of success, longest development time

Broad vs narrow indications Broad indications (eg chronic pain vs chronic cancer pain) –Benefits MDs become more familiar with how to use it Marketing is easier, targets larger set of conditions and perhaps broader range of medical disciplines; larger market value ? helpful for Third Party Payers –Disadvantages MDs may need to use it differently for different indications Harder to obtain broad indication Might encourage MDs to try drug for unapproved uses Narrow indications –Inverse benefits and disadvantages –Tailoring drugs to individual genotypes

Industry challenges from changing regulatory definitions NP example Prior to 2001: for broad indication 2001 – 2005: replicate studies for narrow claim 2006: intermediate indications possible - peripheral, central, and then general for clearly related syndromes (DPN, HIV) for less related syndromes (DPN, PHN) Acute pain example Compartments A, B and C Justification: growth of knowledge NP: requirement for nerve conduction studies May delay NDA submissions, tend to increase the number of clinical trials

Outcome Measures and marketing considerations Ideal new pain drug –Reduces pain, minimal side-effects –Physicians prescribe it – easy to use –Insurers, HMOs pay for it How much medical improvement needed for payers to cover prescription costs? Need outcomes measures to assess overall economic benefit –Reduced office visits, hospitalizations, duration of stay Introduce outcomes measures earlier in drug development Industry partner with payers