Obesity Drug Pipeline: Developing Therapies for a Complex Disease

Table of Contents

Chapter 1; INTRODUCTION: ARE OBESITY DRUGS NEEDED?

• 1.1. The Growing Worldwide Obesity Epidemic
• 1.2. Definition of Obesity
• 1.3. Obesity as a Factor in the Pathogenesis of Major Diseases, Especially Diabetes and Cardiovascular Disease
• 1.4. Social and Economic Change as Drivers of the Obesity Epidemic
• 1.5. Difficulty of Maintaining Long-Term Weight Loss Through Diet and Exercise Alone
• 1.6. Guidelines for the Treatment of Obesity, and the Role of Drugs and Surgery
  • American College of Physicians (ACP) Guidelines
  • Obesity Drugs
  • Lifestyle Modification and the Efficacy of Obesity Drugs
  • The Role of Bariatric Surgery in the ACP Guidelines
• 1.7. Obesity as a Disease, Not the Result of Lack of Willpower
  • Genetic and Physiological Factors in Obesity
  • Small Population Studies to Examine the Interaction of Environmental and Genetic Factors in Obesity
• 1.8. Basic Research Suggesting that Drugs Are Needed in Obesity Treatment

Chapter 2; DIFFICULTIES IN SUCCESSFUL DEVELOPMENT OF OBESITY DRUGS

• 2.1. Barriers to Successful Development of Obesity Drugs
  • The Societal Perception of Obesity as a "Lifestyle Issue"
  • Reimbursement
  • Consumer Payment Out-of-Pocket
  • The Poorly Understood Complexity of the Physiology of Control of Body Weight and Fat Mass
• 2.2. The Complex Genetics of Human Obesity
• 2.3. Continuing Safety Issues Connected with Obesity Drugs

Chapter 3; CURRENT DRUGS AND THEIR INADEQUACIES

• 3.1. Sibutramine
• 3.2. Orlistat (Xenical)
• 3.3. Lack of Sufficiently Safe and Effective Obesity Drugs on the Market Today

Chapter 4; HISTORY OF FAILURE IN THE OBESITY DRUG FIELD

• 4.1. Fenfluramine, Dexfenfluramine, and Fenfluramine/Phentermine
• 4.2. Recombinant Leptin and Recombinant Ciliary Neurotrophic Growth Factor
• 4.3. Rimonabant

Chapter 5; NEXT-GENERATION OBESITY PIPELINE DRUGS

• 5.1. Phase III Agents
  • Phentermine/Topiramate (Qnexa)
  • Buproprion/Naltrexone (Contrave)
  • Lorcaserin
  • Cetilistat
  • Phase III CB1 Inhibitors: Taranabant and CP-945,598
  • Potential of Current Phase III Drugs
• 5.2. Phase II Agents
  • Pramlintide/Metreleptin
  • Liraglutide
  • Zonisamide/Bupropion (Empatic)
  • Tesofensine
  • Peptide YY Nasal Spray
• Potential of Current Phase II Drugs

Chapter 6; SELECTED TRENDS IN EARLY-STAGE APPROACHES TO DEVELOPING OBESITY DRUGS

• 6.1. Drugs that Target Receptors in Core Hypothalamic Energy Balance Pathways
  • Melanocortin Receptor Agonists
  • Neuropeptide Y Receptor Antagonists
  • Melanin-Concentrating Hormone Receptor Antagonists
• 6.2. Novel Drugs that Treat Both Obesity and Diabetes
  • Protein Tyrosine Phosphatase 1B Inhibitors
  • Adenosine Monophosphate - Activated Protein Kinase Activators
  • Ghrelin Antagonists
  • Prospects for Novel Obesity/Diabetes Drugs in Obesity
  • 6.3. Might It be Possible to Develop Obesity Drugs that Increase Energy Utilization in Peripheral Tissues?
  • A Potential Pharmacological Exercise Mimetic
  • Treating Obesity by Increasing Brown Fat Deposits

Chapter 7; OUTLOOK FOR THE OBESITY PIPELINE

• 7.1. Insight Pharma Reports Obesity Drug Development Survey - July 2008
• 7.2. General Conclusions

APPENDIX

• Expert Interviews
• Olivier Boss, PhD, Associate Director of Biology, Sirtris, Cambridge, MA
• Alice Izzo, Executive Director of Corporate Affairs, Amylin Pharmaceuticals, San Diego, CA
• Peter Y. Tam, Senior Vice President of Product and Corporate Development, VIVUS, Mountain View, CA
• David A. Walsey, Director, Corporate Communications, Arena Pharmaceuticals, San Diego, CA

References

Company Index with Web Addresses