Abstract
The prevalence of overweight and obesity is increasing at an alarming rate
worldwide, driven by social and economic changes. Obesity is involved in the
pathogenesis of major diseases, especially diabetes and cardiovascular
disease. Yet there are no sufficiently safe and effective obesity drugs on the
market today. This report analyzes:
- Product pipelines;
- Current obesity drugs and the need for novel therapies;
- Obesity drug markets;
- Challenges to the successful development of obesity drugs;
- The complex disease pathways of obesity and weight regulation.
Many public health experts classify the rise in obesity as an epidemic.
Largely as the result of increased risk for diabetes and cardiovascular
disease, obesity carries an increased risk of premature death. According to an
estimate by the US Centers for Disease Control, approximately 112,000 deaths
per year are associated with obesity. Obesity drugs, however, have been dogged
by safety issues that, in some cases, have resulted in market withdrawal.
Obesity Drug Pipeline: Developing Therapies for a Complex Disease examines the
demand and potential market for novel obesity treatments that are safe and
truly effective.
The report also describes why the physiology of weight control is so complex.
Disease pathways of obesity are poorly understood and appear to be dependent
on many genetic and environmental factors. Researchers and companies have been
using what is known about energy balance pathways to design obesity drugs, as
will be discussed. The report also describes efforts underway to better
understand the complex genetics of human obesity and how these findings can
inform obesity drug discovery.
General barriers to the successful development of obesity drugs are discussed,
including the societal perception of obesity as a "lifestyle issue," not a
medical/pharmacological one. Despite the extensive basic science that
indicates that obesity is a disease, which like other metabolic and
cardiovascular diseases has a complex causation (i.e., genetic, physiological,
lifestyle, environmental, etc.), the traditional view that obesity is merely
an issue of willpower and lifestyle, and even a cosmetic issue, dies hard. In
particular, the idea that obesity is a lifestyle issue and not a disease
affects reimbursement, which may constitute a significant hurdle to the
development of obesity drugs.
Luckily, not all experts agree that these factors constitute an insuperable
hurdle to the successful development and commercialization of new obesity
drugs. Only two drugs are approved in the United States for long-term
treatment of obesity: sibutramine (Abbott' s Meridia/Reductil) and orlistat
(Roche' s Xenical and GlaxoSmithKline' s low-dose, over-the-counter form, alli).
Both are minimally efficacious and have significant side effects, which tend
to discourage their use. Obesity Drug Pipeline: Developing Therapies for a
Complex Disease reviews next-generation obesity drugs, including late-stage
development programs as well as selected early-stage approaches to developing
obesity drugs.
We conclude with expert interviews and an analysis of results from CHI' s
Obesity Drug Discovery & Development Survey, conducted in July 2008.
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
