For now the obesity drug market is a two-horse race. VIVUS' (VVUS) Qsymia has already launched, and Arena Pharmaceuticals' (ARNA) Belviq will hit pharmacies as soon as the Drug Enforcement Agency finalizes its abuse potential. Roche (RHHBY -2.24%) also has a drug on the market, but it's been there for years and hasn't been a big seller. Abbott Labs' (ABT -0.65%) Meridia was pulled off the market a couple of years ago.

For now, all eyes are focused on Qsymia and Belviq, but there's more competition in the works.

Safety first
Orexigen's (NASDAQ: OREX) Contrave had the chance to be become the first obesity drug on the market. An advisory committee gave it a thumbs-up by a nearly 2-1 margin, but the Food and Drug Administration decided the risks weren't defined enough to approve the drug.

The FDA asked Orexigen to run a clinical trial to rule out the possibility that Contrave causes heart problems. Enrollment is proceeding well with the interim analysis that could happen as soon as the second quarter of next year. The company needs to wait for 87 major adverse cardiovascular events -- heart attacks, strokes, and the like -- to occur before doing the analysis.

There are no guarantees that the trial will prove that Contrave has an equivalent risk profile to placebo. Interim analyses have higher statistical thresholds than the full analysis at the end of trials do. It's entirely possible the company will have to wait for the full analysis to prove the drug is safe. Or, worse yet, maybe that hint of potential heart problems the FDA was worried about might actually turn out to be real.

Proof of concept
Privately held Zafgen recently started a phase 2a clinical trial for its obesity drug beloranib. Rather than fighting obesity by reducing appetite, beloranib is designed to restore the balance between the production and utilization of fat.

Studies thus far have looked pretty good. After just four weeks on the drug, patients lost about 10 pounds compared to the placebo group that lost 2.6 pounds in one study and gained a little in the other. Patients taking a larger dose lost even more weight, but the side effects look too severe to use the souped-up version.

The one knock on beloranib is that it has to be injected, but if it can produce substantial weight loss, patients may be willing to tolerate the needle injections, especially considering that if they develop type 2 diabetes, they'll eventually be injecting insulin for the rest of their lives.

Curing those obese monkeys
Amgen (AMGN -0.19%) has developed an antibody, dubbed mimAb1, that activates the Fibroblast Growth Factor 21 complex, which regulates glucose and lipid metabolism. Overactivation of the complex mimics dieting, where expression of FGF21 is increased, without the need to actually starve.

In a preclinical study, obese monkeys lost about 10% of their body weight while on the drug for 11 weeks. They also had lower insulin, glucose, and triglyceride levels. That's a solid result if it translates to humans.

Investors' worse fear
It seems pretty likely that Qsymia and Belviq will have competition at some point in the future. If not by Contrave, beloranib, or mimAb1, then from something else. The potential market is too great for other drugmakers to ignore, especially now that the FDA has lightened up on its hard-lined stance of drugs in the space.

Investors should keep one eye on the sales figures and another on the potential competition in the pipeline. Qsymia and Belviq are decent drugs, but they each have their flaws; Qsymia has safety issues, and Belviq only produces mild weight loss on average. Getting the FDA to change its view of acceptable risk put a target on their back. A big fat obese one.