The buildup to the biggest three-way sumo drug wrestling match investors have ever seen can finally begin. On Wednesday, Orexigen Therapeutics (Nasdaq: OREX) announced that it had been given an FDA advisory committee meeting date, completing the dates for the trio of obesity drugs up for review.

Mark your calendar
If you're going to invest in obesity drugs, keep each and every one of these dates on your mind.

Drug

Company

Advisory Committee

PDUFA date

Qnexa

VIVUS (Nasdaq: VVUS)

July 15, 2010

Oct. 28, 2010

lorcaserin

Arena Pharmaceuticals (Nasdaq: ARNA)

Sept. 16, 2010

Oct. 22, 2010

Contrave

Orexigen

Dec. 7, 2010

Jan. 31, 2011

Source: company releases.

The Food and Drug Administration usually publishes documents for the advisory committee members two business days ahead of the meeting. Expect share prices of the companies to move as investors pore through the documents looking for clues to what FDA reviewers think of the drug. Remember, advisory committees make recommendations, but the FDA has the final say.

PDUFA, which stands for Prescription Drug User Fee Act, gives the FDA a goal of making its decision on New Drug Applications within 10 months. The FDA usually hands down the decision right before the date, but decisions can come earlier or later, so trying to time your trade around the date is usually a bad idea.

Efficacy matters
The biggest hurdle for obesity drugs is the ability to show enough weight loss to justify patients taking them. Since diet and exercise are an option -- even if some people aren't interested in doing that -- it may be difficult to get past the FDA with only a modest effect on weight loss.

Because clinical trials enroll different patient populations, it's a little difficult to compare the results that different drugs put up; each compared its drug candidate to placebo, not each other. Even with that caveat, it sure looks like Qnexa is the winner here, registering a placebo-adjusted weight loss of 9.4% of body weight in one trial and 8.6% of body weight in another.

But don't forget about safety
The FDA is likely to be very cautious about the safety aspects of the drugs. After all, the side effects of exercise -- turf toe, sore muscles and the like -- are fairly mild.  And while obesity causes long-term issues, the immediate threat to health isn't as prevalent as it is for something like cancer. Pfizer (NYSE: PFE), sanofi-aventis, and Merck all dropped development of obesity drugs because of fear that side effects would preclude approval by the FDA.

Qnexa is a mix of one of the parts of Wyeth's fen-phen -- albeit not the part that's believed to cause heart problems -- and Johnson & Johnson's (NYSE: JNJ) migraine and epilepsy drug, Topamax, which has some serious side effects. Qnexa's side effects seemed tolerable in clinical trials, but it remains to be seen how much pause Topamax's history will give the FDA when considering it as a treatment for obese patients.

Lorcaserin seems to have very mild side effects to go along with its mild efficacy data. That may not be a bad position, and the drug could be used as a first-line treatment that might work for some patients. Whether the FDA will buy the argument remains to be seen, but the agency isn't likely to punt the drug based on side effects.

Where does that leave Contrave? Somewhere in the middle. Stuck in limbo is not an ideal position, but Orexigen does have the advantage of going last. Seeing whether the committee concentrates on efficacy or safety in the first two reviews could help Orexigen when presenting its case.

Room for all three?
It's hard to predict exactly what the FDA is going to do with the three applications. I'd rank the probability of approval in this order: Qnexa, lorcaserin, Contrave. But it's not out of the question that all three get turned down or all three get approved.

That uncertainty is built into the stock price with Arena and Orexigen trading at market caps below $320 million. VIVUS is trading closer to $800 million, but it has an erectile-dysfunction drug on the market and another one on the way. The shares are sure to skyrocket on an approval. This is an untapped market after all.

Current offerings like Abbott Labs' (NYSE: ABT) Meridia and GlaxoSmithKline's (NYSE: GSK) alli are pretty pitiful, both in their ability to help people lose weight and their sales. Investors shouldn't be worried about competition. The key for these companies is just to get their drug approved.

Pfizer is a Motley Fool Inside Value recommendation. Johnson & Johnson is an Income Investor recommendation. Motley Fool Options has recommended buying calls on Johnson & Johnson. Try any of our Foolish newsletters today, free for 30 days

Fool contributor Brian Orelli, Ph.D., doesn't own shares of any company mentioned in this article. The Fool owns shares of GlaxoSmithKline and has a disclosure policy.