"No one knows and no one is saying anything," says Donny Wong, senior pharmaceutical analyst at Decision Resources. "We're now in a post-Vioxx, post-Fen Phen world, and both issues are fresh in regulator's minds."

Acomplia is a cannaboid type-1 receptor (CB1) antagonist, often referred to as the "anti-munchie drug." Originally intended to treat obesity, Acomplia's broad range of additional indications—smoking withdrawal, atherosclerosis, alcoholism, liver disorders, and schizophrenia—have expectations over the moon. But side effects like elevated risk of depression were severe enough to require further studies. Earlier this year, FDA gave Sanofi an approvable letter for use in the treatment of obesity, but a non-approvable for smoking cessation.

"Any new obesity drug will be used by millions of people," says Richard Atkinson, chief of the Obetech Obesity research center in Richmond, VA, "so FDA is being exceedingly cautious in approving the drug."

Symbicort AstraZeneca

TARGET INDICATION Asthma/COPD
DEVELOPMENT Approved
LAUNCH DATE 2007

Already released in Europe and slated for US launch in 2007, Symbicort (budesonide/formoterol) by AstraZeneca could be the biggest competitor to the asthma market-leader, GSK's Advair. This twice daily, inhaled medication consists of a corticosteroid—budesonide—and a bronchodilator—formoterol. In addition to curbing the onset of asthma attacks, some clinical tests have shown that Symbicort can provide relief during an attack by opening the airways for easier breathing, and by reducing swelling.

"Formoterol has a slightly faster onset of action and is more dose responsive," says Cindy Mundy, director of immune and inflammatory diseases at Decision Resources. "However, providing physicians with a compelling reason to switch to Symbicort is going to be tough."

The company is hedging its bets on formoterol, a beta-agonist that appears more effective than what's in Advair. –GK

Torcetrapib Pfizer

TARGET INDICATION Cholesterol
DEVELOPMENT Phase III
LAUNCH DATE 2011

Pfizer is staking at least part of its future on being able to extend the success of mega-blockbuster statin Lipitor (atorvastatin)—a drug that represented a quarter of the company's revenue last year. That hope is pegged on torcetrapib, a compound for atherosclerosis that Pfizer will package with Lipitor. Yet the company has hit a few snares, including early data showing that torcetrapib can raise blood pressure. For that reason, FDA is likely to require longer-term data that shows that the drug not only raises good cholesterol but also reduces heart attacks.

"The word from doctors is: What really matters is outcomes data," says Mary Argent-Katawala, senior analyst at Decision Resources.

Yet, if successful, Pfizer's proposed formulation of 40 mg of Lipitor and 60 mg of torcetrapib could be an even bigger success than Lipitor. Torcetrapib is a member of the cholesterol ester transfer protein (CETP) inhibitor class; CETP acts as a key intermediary in the distribution of cholesterol between high- and low-density lipoproteins (HDL, LDL). In theory, by blocking CETP, you improve the ratio of HDL-C to LDL-C and slow the progression of coronary heart disease. Preliminary studies show that torcetrapib/atorvastatin raised HDL ("good" cholesterol) by 56 percent and lowered LDL ("bad" cholesterol) by 27 percent. Lipitor alone lowers LDL by about 39 to 60 percent—better than the combo, but Lipitor alone doesn't provide the positive effects of increasing HDL.

Skeptics, though, charge that the "up with the good" theory on cholesterol needs further investigation. "It's not enough to believe that raising HDL is a good thing," says Chuck Farkas, a cardiovascular drug analyst at Bain & Co. "We have to see it, and it's something we haven't seen yet." –JP AND BH