Obesity Facts

Obesity is a chronic, currently untreatable disease that contributes to the development of type 2 diabetes, cardiovascular diseases, inflammatory diseases, hypertension, aging and some forms of cancer. Obesity is responsible for over 300,000 deaths annually in the US, and recently surpassed smoking as the leading cause of preventable death in the US. The cost to the health care system is in excess of $300 Billion worldwide, and any agent that interrupts the cascade of progressive, debilitating diseases associated with obesity will have major financial and medical impact. The potential market in the US for anti-obesity drugs is expected to exceed $50 Billion annually. Despite the medical need and commercial opportunity, to date the pharmaceutical industry has commercialized only two anti-obesity drugs, Meridia (Abbott) and Xenical (Roche).

There are four approaches for therapeutically intervening in obesity:

  1. Suppress appetite by inhibiting central (CNS) feeding pathways (e.g., ghrelin, neuropeptide Y pathways) or by stimulating central satiety pathways (e.g., melanocortin, brain derived neurotrophic factor pathways),
  2. Block nutrient digestion or absorption within the gastrointestinal tract by inhibiting digestive enzymes (e.g., lipases, glucosidases) or uptake pathways (e.g., microsomal transfer protein),
  3. Reduce fat cell number by inhibiting differentiation of precursor cells (preadipocytes) to mature fat cells (adipocytes), and
  4. Reduce fat cell size by inhibiting synthesis of fat or stimulating the release and/or burning of stored fat.

Abbott's Meridia (Sibutramine, which inhibits reuptake of serotonin, norepinephrine and dopamine) is an example of a centrally acting appetite suppressant and Roche's Xenical, which inhibits pancreatic lipase preventing absorption of fat from the GI tract, is an example of the second approach. Both drugs are reported to have significant side-effects — headaches, elevated blood pressure and tachycardia for Meridia, and flatulence, anal leakage and reduced absorption of fat-soluble vitamins for Xenical — and are of modest efficacy, ~5% weight loss over two years. Though the discovery, preclinical and clinical anti-obesity landscape is quite competitive, most of these efforts are directed to central pathways that regulate appetite with very little attention being given to the pathological tissue in obesity, fat. AdipoGenix's focus on fat is therefore quite distinctive, even in this very crowded arena.

More Information
For additional information on obesity we recommend “The Practical Guide — Identification, Evaluation, and Treatment of Overweight and Obesity in Adults”, which is available at www.nhlbi.nih.gov and information available at the web site for the North American Association for the Study of Obesity, www.naaso.org.