BioWorld Insight Contributing Writer

Vivus Inc., Arena Pharmaceuticals Inc. and Orexigen Therapeutics Inc. all presented data at last week's annual scientific meeting of the Obesity Society, but the chance of any obesity drug making it onto the market has more to do with FDA requirements than subset analyses and extension studies presented at the meeting.

Last month, Vivus said it had reached an agreement with the FDA to apply for a restrictive label stating that Qnexa (phentermine/topiramate) should only be used by men and women without childbearing potential because of the potential risk of major congenital malformations and oral cleft in offspring of women exposed to topiramate during pregnancy. Vivus is running a retrospective observational study called FORTRESS – for Fetal Outcome Retrospective TopiRamate ExpoSure Study – which may allow the firm to apply for a broader approval after the data is validated next year. (See BioWorld Today, Sept. 16, 2011.)

About a week later, Orexigen announced it had established a pathway forward for Contrave (naltrexone HCI/bupropion HCI) after the agency backtracked from requiring a large clinical trial measuring cardiovascular risk that the company saw as unfeasible. The new agreement calls for a trial that could be completed as early as 2014. (See BioWorld Today, Sept. 22, 2011.)

Arena continues to work though its FDA to-do list. Most recently, the biotech announced that a re-adjudication of female rat mammary tumor diagnoses from a two-year rat carcinogenicity study concluded that lower doses of lorcaserin didn't increase the incidence of malignant mammary tumors.

BioWorld Insight poured through 11 different opinions on the three companies by seven different analysts, and the only conclusion to draw is that there's little in the way of a consensus of opinion. Handicapping this race is difficult at best.

For instance, J.P. Morgan analyst Cory Kasimov was bullish on the accelerated filing for Qnexa. "Overall, we believe this is a reasonable strategy that could accelerate the potential time to market by about a quarter and increase the probability of initial approval," Kasimov wrote.

But Jefferies & Co. analyst Thomas Wei didn't see the silver lining in Vivus' announcement in part because there's more to the story than just potential birth defects. "We believe that investors have understated the FDA's residual concern on a Qnexa-specific cardiovascular risk and the potential for the FDA to implement general CV safety testing for all obesity drugs," Wei wrote.

Even the impact of the FDA-blessed plans on the other companies in the field was greeted with mixed opinion.

Kasimov saw Orexigen's agreement with the FDA as a good sign for the entire sector. "We believe this development represents another indication of political pressure on the FDA having some success in trying to foster a more industry-friendly environment for obesity drug development," Kasimov wrote.

But Jim Birchenough, biotechnology analyst at BMO Capital Markets, wasn't as convinced that the agreement was a good sign for Arena. "We see limited positive implications for Arena in FDA following prior FDA panel advice for large CV outcomes studies in advance of obesity drug approvals and see increased risk that similar studies will be required for Arena's Lorquess."

And perhaps the biggest problem plaguing the industry, making it hard to determine the likelihood of approvals, is the lack of guarantees that FDA-company agreements will hold up.

"FDA promises and pie crusts are made to be broken," wrote Jefferies & Co. analyst Corey Davis about Orexigen's agreement.