July 13, 2010

FDA Reviewing Three Weight Loss Drugs

Doctors are getting their first glimpse at a new weight loss drug this week.

The doctors hope that the drug, which is one of three new weight loss drugs coming out, can succeed where many others have failed by delivering significant weight loss without risky side effects.

With U.S. Obesity rates closing in at 35 percent of the adult population, expectations are high for the first new prescription drug therapies that have been emerging for over a decade.  Even a modestly effective drug has blockbuster potential.

None of the three drugs coming out represent a breakthrough in research.

Drugmakers have made little headway in understanding and treating the causes of overeating.  Two of the drugs submitted for approval are a combination of existing drugs, an anticonvulsant and an amphetamine.  The third, a new medication, is less effective than the other two, but said to be safer.

The search for developing a weight loss drug has been plagued for decades by safety issues.  The most notable was Wyeth's diet pill drug combination fen-phen, which was pulled off the market in 1997 because of its links to heart valve damage and lung problems.

The FDA was expected to post its review of Vivus Inc.'s pill Qnexa on Monday and hold a public meeting Thursday to review the data.  Arena Pharmaceuticals Inc.'s Iorcaserin is set to go under an FDA panel for review in September, while Orexigen Therapeutics's Contrave will be the subject of review in December.

"There's no obvious clear winner," Leerink Swann analyst Steve Yoo told The Associated Press (AP). "If you look at different aspects, each drug shines."

According to FDA guidelines, to be considered effective obesity drugs should reduce total body weight by at least 5 percent after one year.

Qnexa showed the best weight loss results in clinical trials where patients lost between 13 percent and 15 percent of their body weight.  However, the drug also had the highest rate of patient dropouts because of side effects, such as memory and concentration problems.
Qnexa is a combination of the amphetamine phentermine and topiramate, an anticonvulsant drug sold by Johnson & Johnson as Topamax.  According to the company, phentermine helps suppress appetite, while topiramate makes patients feel more satiated.

Contrave is also a combination pill that mixes an antidepressant with an anti-addiction drug.  The drug shows a weight loss of between 5 and 10 percent with side effects such as nausea.

Jason Halford, a University of Liverpool Professor, told AP that drug companies are taking a multi-pronged approach to obesity therapies because science has shown there are multiple brain signals that drive food intake.

"We're using combinations of old drugs with a very broad spectrum of pharmacotherapy, it's very much the shotgun approach," said Halford, a health psychologist who has consulted for drug companies on obesity treatments.

The one truly novel drug under FDA review showed the weakest results in clinical trials.  Arena Pharmaceuticals' lorcaserin is a first-of-a-kind drug that acts on serotonin receptors.  However, patients in company trials lost just 5 percent of their body weight while on the drug.

Although Arena's drug is behind competitors in weight loss, it appears to have the least amount of side effects, which is an important factor in gaining FDA approval.

The history of diet drugs has been littered with stumbling blocks.
The diet drug fenfluramin was withdrawn in 1997 after it was linked with heart damage.  The drug's combination with phentermine was popular but never approved by FDA.

Sanofi-Aventis SA discontinued studies two years ago of its highly anticipated pill Acomplia because of psychiatric side effects, including depression and suicidal thoughts.

Side effects have kept weight-loss drugs currently available on the market from being blockbuster sellers.  Abbott Laboratories' appetite suppressant Meridia was pulled from the market in Europe last November because of data showing increased heart attack risks.  The FDA warned consumers in May that the over-the-counter weight loss pill "Ëœalli', which has been sold for years at a higher dose as the prescription drug Xenical, could cause severe liver damage. The drug works by limiting the amount of fat the body absorbs.

Pharmaceutical researcher and blogger Derek Lowe said that the new combination of drugs under review hold promise because they work on multiple brain chemicals that drive overeating.

"No single agent is going to shut down this behavior," Lowe wrote in a blog entitled "In the Pipeline.  He added, "But if you can come in and hit two or more of these different pathways at the same time, maybe then you'll get somewhere."


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