New Diet Drug Attacks Craving Center

July 21, 2009— -- Finding the perfect pill, procedure, or injection to make people lose weight might sound as lofty a goal as genetically engineering a money tree. But drug companies are still trying.

Yesterday the makers of a new weight-loss drug called Contrave announced their clinical trials actually exceeded the U.S. Food and Drug Administration's requirements to prove a weight loss drug's effectiveness.

People taking the drug lost an average of 8 percent of their body weight (around 17 pounds) within one year compared with people on the placebo, who lost an average of 1 percent of their body weight in a year.

"This is the first drug, that I know of, that addressed the craving issue," said Dr. Dennis Kim, senior vice president of medical affairs and communications at Orexigen Therapeutics Inc., maker of Contrave.

"We have clearly cleared the hurdle, the efficacy benchmark, it's of course the FDA's judgment to see if it passes for safety," said Kim, who is also an assistant professor of medicine at University of California, San Diego.

The most common side effects included nausea, constipation and headache. The most severe side effects were one case of gall bladder infection and one person who had seizures. More than 3,000 people were included in the study, but around 40 percent of them dropped out of the trial.

Despite the success in terms of FDA efficacy standards, many obesity specialists voiced caution over the drug, or any weight loss drug.

"I have limited enthusiasm for pharmacotherapy to manage weight, and these results certainly don't change my view on the topic," said Dr. David Katz, associate professor Public Health at Yale University and expert in obesity. "The results are promising, although certainly less than dazzling."

Katz said he thought the Contrave results were "fairly consistent" with the success of other drugs for weight loss.

"Perhaps the single uniquely promising element here is that Contrave is a combination of two drugs long in use for other purposes, and thus likely to be at least relatively safe," Katz wrote in an e-mail to ABC News.

Contrave is the first drug to combine a anti-depression and smoking cessation drug called bupropion and naltrexone, prescribed to fight alcohol and opiate addiction.

Weight Loss Pill That Targets the Brain's Cravings

The point with Contrave, Kim said, isn't to increase metabolism but to block the craving in the craving-reward system in the brain.

"It's not so much the reaction to whatever you're doing, it's more the craving about those activities," said Kim, who added that because the drug targets craving and not reward that patients are less likely to experience diminished enjoyment in exercise or sex.

Other weight-loss drugs on the market also target the brain or central nervous system rather than the metabolism. For example Meridia (or sibutramine) works as an appetite suppressant by boosting chemical messages that tell the brain you're satisfied.

Based on the long-term outcomes of other weight-loss drugs that target the brain, Katz was cautious about the promise of Contrave.

"Weight is regulated by many pathways, and to date, efforts to turn off appetite along one pathway have resulted in compensation in others," he said.

Only time will tell for Contrave. With the FDA bar for efficacy out of the way, the makers of Contrave say they are about to seek FDA approval for the drug in early 2010, which is not guaranteed.

Whether or not Contrave is approved, some doctors predict the approach behind the drug will become a trend in obesity treatment.

"There is no question that drugs like Contrave are the way of the future," said Dr. Mitchell Roslin, of Lenox Hill Hospital in New York City. "For obesity drugs to be effective they will need to be this type of cocktail that hits multiple targets."

Kim said the weight-loss results that came with that approach had some additional health advantages -- patients feeling less grumpy, for example, lower LDL or "bad cholesterol" levels, lower triglycerides, less visceral fat between the organs and smaller waists. Diabetic patients on the drug also showed better control of their blood glucose levels.

What the FDA Asks of Weight-Loss Drug

The FDA requires at least a third of the patients on a weight-loss drug lose 5 percent of their body weight to call the drug effective. Of the people taking Contrave in two non-diabetic clinical trials, nearly half (48 -56 percent) lost more than 5 percent of their body weight in a year.

Contrave also exceeded the FDA expectation that twice as many people on the drug hit the 5 percent body weight goal as people on the placebo. In the two non-diabetic trials, three times more people hit the 5 percent reduction in body weight on the drug than on the placebo.

Keith Ayoob, director of the nutrition clinic at the Albert Einstein College of Medicine in Bronx, N.Y., wasn't exactly blown over by the results.

"This drug seems to have an edge on the others out there. It appears to have met the FDA criteria and there is a reasonable amount of weight loss over a year's time. However, let's keep real about this," said Ayoob. "Fifty six weeks is a long time to lose only 5 percent of weight. For a 200 pound person that amounts to 10 pounds in a year."

"It's good, no question, and better than placebos, but I wouldn't want people thinking this is some sort of miracle," he said.

Ayoob points out that the drug works by controlling cravings, but that people often overeat and become obese for other reasons.

Other doctors were concerned about what would happen if patients take the drug for a long period of time.

"Most significantly, what happens when the drug is stopped? Will the weight be regained? What will be the effects of years of use of these drugs?" said Katz. "Despite these issues, this is exciting data."

Kim said the FDA usually asks for year-long studies in drugs that are intended for chronic use, and predicts Contrave will be prescribed for long-term use.

"There will be a small number of patients who will be able to get off these drugs," said Kim. "But the vast majority of patients would probably need to take this medication chronically."