Contributing Writer

Orexigen Therapeutics Inc.'s obesity drug Contrave (naltrexone SR/bupropion SR) heads in front of an FDA advisory panel on Tuesday.

If it feels like we've seen this story line before, that's because we have – twice to be exact. Vivus Inc.'s Qnexa (phentermine/topiramate) and Arena Pharmaceuticals Inc.'s lorcaserin were both voted down by the Endocrinologic and Metabolic Drugs Advisory Committee earlier this year. Both obesity drugs subsequently received complete response letters (CRL) from the FDA. (See BioWorld Today, July 16, 2010, and Sep. 17, 2010.)

Going last could give Orexigen an edge. Steve Weisman, partner at consulting firm Innovative Science Solutions, thinks there's some advantage to being late to the party. "Going last helped [Orexigen] learn about the sensitivities of the advisory panel," he told BioWorld Insight.

Weisman points to the H2 receptor antagonists switching to over-the-counter status as an example of how companies can benefit from watching the experiences of drugs that were first to market. On their first attempt to switch to OTC status, the FDA turned down SmithKline Beecham plc's Tagamet HB and Johnson & Johnson-Merck Consumer Pharmaceuticals Co.'s Pepcid AC. By the time Axid (nizatidine) came around, SmithKline Beecham had figured out what the FDA required for approval.

Similarly, watching the experiences of Prilosec (omeprazole) helped companies gain approvals of other proton pump inhibitors such as Prevacid (lansoprazole) and Nexium (esomepraxole magnesium).

The drugs that came later "benefited from clarity around what would be expected," said Weisman.

While the FDA advisory panels were open to the public, there's no way for Orexigen to know all the details of why the FDA rejected Qnexa and lorcaserin since the CRLs from the FDA aren't public. Weisman doesn't think the private communication between the agency and the company necessarily needs to be public, but he said the publicly released information was enough to guide the preparations for Orexigen's upcoming advisory committee meeting.

Leerink Swann analyst Joshua Schimmer also thinks Orexigen should be well prepared. In a research note, he said he believes Orexigen will benefit from having watched Arena and Vivus present at their respective panel meetings.

But whether or not good preparation will be enough to overcome safety concerns remains to be seen. J.P. Morgan analyst Cory Kasimov thinks Orexigen's chances are about as good as a coin flip. "We continue to ascribe a 45 percent probability of a positive outcome," he wrote in an investor note.

Schimmer and Kasimov didn't see anything in Friday morning's FDA briefing documents that was a surprise to them, but investors were less than thrilled, sending Orexigen's shares down by as much as 14.6 percent in early trading. (See BioWorld Today, Dec. 6, 2010.)

Orexigen's best hope for getting past the FDA advisory committee is to convince the panel that the safety concerns can be taken care of after the FDA approves the drug. For each of the safety concerns – psychiatric adverse events, seizures, serum creatinine, and heart rate and blood pressure – the FDA's proposed questions for the panel specifically ask if additional studies can address the issue pre- or post approval.

Weisman wasn't excited about Contrave's chances when BioWorld Insight talked to him ahead of the FDA releasing documents for the panel. He thinks weight management drugs are viewed as "lifestyle" products by the FDA, similar to Boehringer Ingelheim GmbH's female sexual dysfunction drug, flibanserin, which was shot down by an advisory panel in a 10-to-1 vote. (See BioWorld Today, June 17, 2010.)

"Very basic preclinical data is being used to turn down the drugs which would never happen for a drug that treats cancer or heart disease," he added. Going last may be an advantage, but it doesn't move the high efficacy and safety bar that obesity drugs have to jump over. "The rigidity will apply to [Orexigen] as it has to others," said Weisman.