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Why the FDA Will Likely Reject 3 New Weight Loss Drugs

By Jim Edwards

Updated on: July 12, 2010 / 12:38 PM EDT / MoneyWatch

The first of three new diet drugs -- Vivus (VVUS)'s Qnexa -- comes up for a vote at the FDA on July 15, and its fate will send a strong signal about the likelihood of its two rivals (Arena (ARNA)'s lorcaserin and Orexigen (OREX)'s Contrave) also getting a thumbs up. The mood surrounding lifestyle drugs has darkened at the FDA, suggesting that all three may get rejected.

The feds almost unanimously kicked out Boehringer Ingelheim's flibanserin, a re-purposed antidepressant for female libido, on both safety and efficacy grounds even though the drug did not display any particularly worrying side effects.

As all three diet drugs have either safety or efficacy concerns, the chances of any of them getting the green light seem reduced. There are no FDA briefing documents available for any of the drugs yet -- although we do know that the FDA insists any drug be at least 5 percent more effective than a placebo -- so let's recap what we know about each:

Vivus's Qnexa: is a combination of phentermine (a bit like speed) and the anti-seizure drug topiramate, commonly known as Topamax. Efficacy: 59 - 84 percent in a study lost 5 percent or more of their body weight. Those on placebo lost 26 percent. Safety: Phentermine can be habit forming and can have cardiovascular side effects. The warnings for Topiramate include kidney stones, suicide and a type of ammonia poisoning. (hyperammonemia and encephalopathy).
Arena's lorcaserin: This is a new drug and so much less is known about it than the combinations of existing drugs that the other two companies are proposing. Efficacy: "More than twice as many lorcaserin patients (47.1%) achieved at least 5% body weight loss compared to placebo (22.6%)," the company says. However on average patients lost 7.9 percent of their body weight, whereas placebo-takers lost 3.9 percent. That seems to be less than the FDA's 5 percent better standard. Safety: The company reports few side effects. Lorcaserin seems to be the safest drug of the three. In a study of abuse potential, Arena says the drug has low abuse potential, but it tested lorcaserin against Ambien (a sleeping pill controlled by the DEA) and ketamine (a veterinary anesthetic better known as Special K to the nightclub crowd), which doesn't seem like a tough competition to win.
Orexigen's Contrave: is a combination of naltrexone, used to fight alcohol and drug addiction (as Vivitrol), and the antidepressant bupropion. Efficacy: 11.9 - 15.7 percent of patients on Contrave lost more than 10 percent of their weight. Placebo takers lost 2 - 2.4 percent. Safety: "Seven serious adverse events were attributed by investigators as possibly related to Contrave treatment. These include cholecystitis (gallbladder inflammation) , seizure, palpitations, paresthesia and vertigo," the company says. Most seriously, naltrexone already carries a black box warning for liver damage, with a narrow range between safe and dangerous doses. Buproprion, already on the market as Wellbutrin, carries a boxed warning for suicide.

Of the three drugs, Contrave appears least likely to be approved. Two boxed warnings equals two red flags, surely, especially for patients whose cardiovascular systems are already under stress from excessive weight. And if Qnexa, the first horse out of the gate, gets rejected, then Lorcaserin must surely be doubtful also.

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Image by Flickr user colros, CC.