Axokine was another anti-obesity drug under development that mimiced a chemical the brain makes to protect itself from injury. Originally designed as a possible treatment for Lou Gehrig's disease, when researchers gave the experimental drug to patients, they lost weight.

The drug affected a powerful brain system called the leptin pathway. Leptin is a chemical messenger that tells you when you've had enough to eat. Obese people have leptin resistance; they lose the ability to know when they're full. Axokine apparently bypasses this resistance and flips the fullness switch.

Regeneron Pharmaceuticals Inc., the developer of Axokine, conducted an early trial of the drug's potential as a weight-loss agent in obese people. They put 173 of these volunteers on a low-calorie diet. Some got placebo injections. Others got various injection doses of Axokine.

After 12 weeks, those on the diet alone had gained about a fifth of a pound. Those getting what turned out to be the optimum dose of Axokine lost an average of nine pounds. In a one-year followup, researchers found no immediate weight gain occurred when drug treatment stopped, but some gain began to occur after about a year.

A high rate of side effects was reported for patients on Axokine, including skin reactions at the site of injection, nausea, and increased cough.

A large Phase III clinical trial produced extremely disappointing results. More than two thirds of the patients taking Axokine developed antibodies, which resulted in less weight loss than seen in earlier trials.

The results of the one year study suggested that Axokine is not very effective long-term, especially considering that it has to be injected.

On March 31, 2003, as a result of awareness that antibodies had significantly impacted the efficacy and marketability of Axokine, the price of Regeneron shares dived and closed down more than 50 percent from the previous day.

SOURCE: The Journal of the American Medical Association, April 9, 2003 and subsequent media reports.