Conspiracy theories seem to be all the rage these days, so the cynic might say that the fast-food industry is in cahoots with the pharmaceutical industry. One makes millions fattening us up and the other empties our wallets as we try to slim down. However, whatever the cause, there is no denying that obesity is a problem in the United States--a problem of epidemic proportions. And while there is no replacement for exercise and eating a healthy diet, there are many of us who, for reasons that can range from depression to genetic predisposition to other complicating health problems, need an extra pharmaceutical push to move them in the right direction when it comes to weight loss. For them, and for the pharmaceutical companies that finally find the right formula, great benefits await.

Recently, there were a string of high-profile, big, fat failures in the obesity pharmaceutical market. The most-recent string of bad luck started back in the '90s, when the anti-obesity medication Fen-phen--a combination of two drugs--was found to cause heart disease, resulting in Wyeth pulling the product from the market and, of course, billions of dollars in lawsuits ensued. Since then, the FDA has been, understandably, not very shy about rejecting weight loss drugs or pulling existing ones off the market.

Since the mainstream media likes to count in threes, for some reason, the recent rejection of a third anti-obesity drug, Contrave by Orexigen, had many pundits declaring a total strikeout, when combined with the rejections of Arena Pharmaceuticals' lorcaserin and Vivus' Qnexa.

As it stands now, the only anti-obesity drug on the market is Xenical from Roche, which reduces intestinal fat absorption. A lower-dose, over-the-counter version of the drug is sold under the name Alli.

Despite high-profile, short-term failures, the anti-obesity market remains promising. According to research and markets, the global anti-obesity market was valued at $1.1 billion in 2009. It is forecast to grow at a Compound Annual Growth Rate of seven percent for the next seven years to reach $2 billion by 2017.

Pulled from the market

Obesity drugs need to show sustained benefit for at least a year. The FDA wants to see obesity drugs deliver an average of five percent of improved weight loss over placebo.

• Meridia - Abbott Laboratories
  Meridia was first suspended in Europe because of stroke and heart attack risks associated with the drug, then in October 2010 was pulled from the market in the U.S., too. Meridia is an oral anorexiant.
  
  
• Acomplia - Sanofi-Aventis
  Sanofi pulled Acomplia off the market in Europe after a 2008 study confirmed that it boosted the risk of psychiatric side effects in some patients. It never won FDA approval for sale in the United States.

In clinical trials

A trio of late-stage obesity drugs have all been shot down by the FDA, leading analysts to question whether the entire field is a loss. But there are early-stage drugs from companies with new ideas about how to treat the disease that could prove successful in the future.

• Lorcaserin - Arena Pharmaceuticals
  Arena's obesity treatment, lorcaserin, was rejected by the FDA because of what it called "marginal" effectiveness, in addition to the problem of rats forming tumors when given the drug in high doses. The FDA is also worried about the pill's potential to be abused.
  
  
• Contrave - Orexigen
  Before its rejection by the FDA, Orexigen had been trying to promote its drugs, Contrave, as a solution for what is becoming known as "diabesity," a buzzword meaning a combination of obesity and diabetes. These plans were shot down by the FDA, which had rejected its application and demanded a pre-approval cardiovascular study before it rules on an approval.
  
  
• Qnexa - Vivus
  Vivus's anti-obesity drug Qnexa, which is a combination of phentermine and topiramate, was rejected by the FDA over concerns about negative effects on concentration and memory. Also, the FDA has asked to see more data on a possible birth defect link to one of its ingredients.
  
  
• Zafgen, based in Cambridge
  Unlike lorcaserin, Contrave and Qnexa, which are in Phase III trials, Zafgen's ZGN-433 is in early-stage testing. It works by resetting the way the body metabolizes fat and has produced consistent weight loss in animal studies. The company has also reformulated its product into a more convenient form, an injection that can deliver the drug just under the skin, instead of via an IV infusion. ZGN-433 has shown promise in early human clinical trials; next step is a Phase II study.
  
  
• Gelesis
  One hot area of obesity research is to attack the problem at one of its sources: our own hungry stomachs. Make us feel full all the time, and maybe we'll be less likely to pounce on the junk food, or overeat. Gelesis is developing capsule that expands in the stomach to make people feel full and eat less. Results from animal trials and early human studies are promising.

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