Pipeline for New Drugs and Potential New Generic Drugs

1. Pipeline for New Drugs andPotential New Generic Drugs By Marv Shepherd, Ph.D. Director Center for Pharmacoeconomic Studies University of Texas Austin, Texas Email: marvshepherd@mail.utexas.edu

2. Presentation Objectives • Trend in costs for drug development. • Overview of the problems with the drug development process. • Examine the decline in new drug products. • List of potential new drugs for 2005. • Shop the expanding generic market. • List of potential new generic drugs. Property of Marv Shepherd

3. Trend in Domestic R&D for Pharmaceutical Companies($Billions) *Value for 2004 is an estimate Property of Marv Shepherd

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5. Decrease in New Drug Approvals • Despite the increase in R&D investment fewer drugs are being submitted to FDA for approval. • Many believe that the industry has not kept up with the new developments in the biomedical sciences. • In other words, the industry is having troubles taking the promise of biomedical sciences and putting them into clinical applications. Look at the decrease in NDAs. Property of Marv Shepherd

6. Source: FDA.gov Property of Marv Shepherd

7. Number of New Approved Chemical Entities 1985-2003 Property of Marv Shepherd

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9. Although there has be a decreasing trend in the number of new drug products, 2004 should be a better year than 2003. • As of September, 2004 there were 16 new chemical entities approved and 69 new drug applications—compared with 21 and 72 in 2003. • Perhaps an upswing in the number of new drug discoveries is coming. Property of Marv Shepherd

10. FDA has stated that there is an urgent need to improve the process of clinical testing including trial design, end points and analyses. • Unacceptable drug performance in the clinical trials is very high; one out every two drugs in clinical trials doesn’t make it to an NDA. • Clinical testing is the most expensive part of drug development, improvements are needed to identify potential products. Property of Marv Shepherd

11. Development Costs • Drug development costs is directly related to disease being treated. • For example, analgesics/anesthetic drugs are the cheapest to develop requiring on average $350 million in clinical costs, whereas CNS drugs cost on average $525 million in clinical costs. (Med Ad News, supplement, 2004) • These are just clinical trial costs. Total drug development cost can run from less than $500 million to $1.5 billion depending on the product/disease. Property of Marv Shepherd

12. Clinical Trial Time Differences by Therapeutic Area • Analgesics/anesthetics-----61.8 months • Anti-infective agents---------63.0 months • Cardiovascular-----------------82.0 months • CNS agents--------------------114.6 months • All drugs--------------------------90.3 months Property of Marv Shepherd

13. New Drug Development • The clinical trial testing costs of developing a new drug have increased 55% since 1999. Tests are requiring more patients, more trials and more long-term monitoring. • Problem: The industry is spending more money, but producing less. Property of Marv Shepherd

14. In response, research from the top 15 pharmaceutical firms are more interested in developing drugs from high net-return therapeutic areas rather than low-net returning areas. Thus, they are not interested in developing analgesic nor anesthetic drugs; they are interested in cancer drugs, cardiovascular agents and CNS drugs (depression, anxiety, schizophrenia, Alzheimer’s disease). Property of Marv Shepherd

15. Promising New Drugs for 2005 • Varenicline® (Pfizer) smoking cessation product. Easing the craving and withdrawal symptoms from nicotine. In clinical trials, half the patients quite smoking within seven weeks compared to 19% on placebo. Product could be launched in 2005. • Lyrica ® (Pfizer) first agent to treat neuropathic pain associated with diabetic peripheral neuropathy and shingles. Received FDA approval December 2004. Property of Marv Shepherd

16. Continuation: Other New Products • Arcoxia ® (Merck) a Cox 2 inhibitor approved in October for osteoarthritis, rheumatoid arthritis, chronic low back pain and dysmenorrhea. However, FDA has asked for more data on long-term use of the product. • Tygracil ® (Wyeth) an antibiotic which is an alternative to IV antibiotics which are increasingly becoming ineffective due to resistance. • Exubera® (Sanofi-Aventis and Pfizer) an inhaled insulin powder taken prior to eating. FDA decision in 2005. Property of Marv Shepherd

17. Continuation: Other New Products • Wyeth is also conducting research on new low-dose birth control pill, Librel ®. The product is in phase III development. Librel ® causes continuous suppression of ovulation allowing women to be period free. • Clofarabine ® also known as Clolar ® (Genzyme) is a promising treatment for leukemia in children and solid cancer tumors which have fail chemotherapy. FDA approved the drug in January 2005. • Entecavirfor ® (BMS) treatment of hepatitis B. Approval is expected late 2005. Property of Marv Shepherd

18. Other Promising Products • Abatacept® (BMS) treatment for arthritis. First- in-class T-cell costimuation modulator. Clinical trial data is impressive, expected to be on the market in late 2005. • Acomplia ® (Sanofi-Aventis) weight-loss drug. Very promising results from clinical trial data. Has created a lot of media attention. NDA is expected to be submitted in spring 2005. • Macugen ® (Eyetech and Pfizer) first therapy for slow vision loss for people with wet age-related macular degeneration. FDA approved in December 2004. Property of Marv Shepherd

19. Other Promising Products • Freestyle Navigator ® (Abbott) is a glucose sensor inserted under the skin. It is paired with a wireless monitor, which can be placed in a purse or on a belt. Monitor sounds an alarm when the glucose level is abnormal. It also stores data. FDA decision expected in 2005. Property of Marv Shepherd

20. Promise of New Generic Drugs Property of Marv Shepherd

21. Source: Med Ad News, May 2004 Property of Marv Shepherd

22. Source: Med Ad News, May 2004 Property of Marv Shepherd

23. Source: Med Ad News, May 2004 Property of Marv Shepherd

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25. Generic Development of Selected Biotech Products, 2003 Sales Property of Marv Shepherd

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27. Conclusion Although in recent years there has been a decreasing trend in the number of new chemical entities, in 2004 the trend may have leveled out or slightly increased. A number of new innovative drug products will enter the market in 2005. Basic science research is more than just a step ahead of translational research to get new products on the market. Inefficiencies in drug research needs to be corrected. patents on over $5 billion of brand name drugs will expire in 2005 and over the next four years, patents on over $30 billion dollars will expire. This will bring an estimated savings to consumers of $12 billion. Property of Marv Shepherd

28. Thanks you very much. Any Questions? Hope you have a nice stay in San Antonio and a successful conference. Marv Shepherd Property of Marv Shepherd