Can Orexigen and its partner Takeda escape the weight-drug jinx?

If Orexigen wins FDA approval for its weight loss drug NB32 (which used to be called Contrave) by tomorrow's long-awaited PDUFA date--and the odds are in its favor--look for the biotech and its pharma partner Takeda to barrel into a huge obesity market that has provided a chilly reception for a pair of rivals.

Orexigen ($OREX) all but threw in the towel back in 2011, when the agency insisted on a new late-stage study to nail down clear evidence of its safety. But the biotech eventually decided to come up with the $100 million needed for the additional trial. An interim analysis last fall on the 10,000 patients recruited for the study confirmed what the biotech was looking for, setting the stage for a resubmission, and tomorrow marks the agency's deadline for a final decision. A green light from the FDA will release a hefty sales force of Takeda reps--an advantage that Orexigen CEO Michael Narachi has repeatedly held up as his trump card in the coming gamble.

"Of the three, Takeda has 10 to 15 years' experience in the diabetes marketplace, and that could play to their advantage," Wells Fargo's Matthew Andrews told CNBC's Meg Tirrell. "That, along with 900 reps, could put them in a good position to outperform Street expectations over the next year or so."

Over the last few months, Orexigen's stock price has climbed steadily higher as investors bought into that scenario.

NB32 will be up against a pair of rivals that has never established a solid hold on this market. Arena (Belviq) and Vivus (Qsymia) won approvals for the first new weight-loss pills in more than a decade back in 2012, but each has struggled to rack up significant sales. They are controlled substances, which seriously delayed Belviq's market entry until last June. A number of payers won't reimburse for the drugs. The effects on weight loss are widely considered marginal among physicians. And past safety issues have left a lingering fear among prospective customers.

A mystery investment firm called Aspen Investments has recently been circling a troubled Vivus ($VVUS), which has seen an upheaval in the executive ranks as its sales efforts have failed to generate much cash. And while Arena ($ARNA) has done better, as its partner Eisai has beefed up its sales effort, the company has also disappointed analysts in recent quarters.

Orexigen and Takeda may be able to counter safety fears with an expanded database. But after the experiences of the last two years, no one thinks it will be easy.

There's also a wild card in the stack. Zafgen, which recently filed for an IPO, has been testing a drug that has the potential to be far more effective in reducing fat. A better drug with a track record on safety could leave all three of the pioneers far behind. So no matter how well Orexigen does with its drug out of the gate, questions about its longterm performance are likely to linger. -- John Carroll, editor-in-chief (email | Twitter)