Obesity Drug Pipeline: Developing Therapies for a Complex Disease

Author: Allan B. Haberman, PhD

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