Vivus’ Qnexa for Obesity: Connecting Activities With Adverse Effects?
Jul13

Vivus’ Qnexa for Obesity: Connecting Activities With Adverse Effects?

Today FDA posted briefing documents about Vivus' experimental weight-loss drug Qnexa. Recall that an FDA advisory committee is scheduled to meet this Thursday, July 15th, to discuss any concerns about the drug and give it either a thumbs-up or thumbs-down recommendation to the agency. Biotech journalist Lisa LaMotta of Minyanville had a great post earlier today on this subject, and she explains why these briefing documents are important. Historically, briefing documents can be a great indicator of how the eventual meeting will pan out. These documents usually show how the FDA is thinking and what questions will ultimately be raised when it comes time for an approval decision. (Although the FDA doesn’t have to follow the advice of the panel, they often do.) FDA's documents suggest that they've got no beef with Qnexa's efficacy- the stuff helps patients lose weight quite well. But the committee has safety concerns in five areas: effects on pregnant women cardiovascular risks psychiatric events cognitive events metabolic acidosis Today I tried to find a molecular link for some of these adverse effects and didn't find anything that was clear to me. Part of the problem is that scientists still aren't sure how topiramate, the monosaccharide molecule in the Qnexa combo, works. Now I'm not saying that's a bad thing. After all, we didn't know how aspirin worked for almost 100 years after it was on the market. But the chemist in me always loves to know more. Here's some of what I found. From a document at FDA's website: Topiramate appears to block voltage-dependent sodium channels Topiramate enhances the neurotransmitter GABA's activity at certain receptors Topiramate antagonizes a specific kind of glutamate receptor Topiramate blocks the enzyme carbonic anhydrase So there you have it. That's a lot of different activities for one little sugar molecule. It seems like it would be easier to connect some of these targets with a psychiatric adverse effect than it would be to say, effects on a fetus. But I'm just grasping at straws there....

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Obesity Musings On Alkermes, J&J News
May25

Obesity Musings On Alkermes, J&J News

I am always on the lookout for news in the obesity drug area. But lately two of the molecular components of experimental obesity drugs in late-stage clinical trials-naltrexone and topiramate- are in the news for other reasons. Alkermes announced this morning that it will receive priority review from FDA for VIVITROL, an injectable extended-release formulation of naltrexone, for treating opioid-dependent patients, with a PDUFA date of October 12, 2010. The idea is that a once-monthly injection of VIVITROL would be given to lower cravings in people with a dependence on opioids such as heroin, Vicodin, or Oxycontin. VIVITROL is already approved for treating alcohol dependence. It's Alkermes's formulation that's new. Naltrexone as a chemical entity has been around for some time. DuPont originally marketed it as Trexan in 1984 but that form is now off-patent, as C&EN's Ann Thayer wrote back in 2006. I also promised that there was an obesity connection here, and indeed there is. Naltrexone is one of the two components in Orexigen's experimental obesity medication, Contrave, as I explained last year. Orexigen has developed its own proprietary sustained-release formulation of naltrexone and the experimental drug's other active ingredient-bupropion, an antidepressant and smoking-cessation aid that boosts dopamine signaling. Ortho-McNeil Pharmaceutical, a subsidiary of Johnson & Johnson, has agreed to pay $81 million (that's $6.1 million in criminal fines and $75.37 million from civil suits) for promoting its epilepsy medication Topamax for several uses not approved by FDA. This story has been in the news for nearly a month now (see Pharmalot's entry about it here) but the company pled guilty to the illegal marketing just last Friday, placing this item back at the top of my Google News list. One of the off-label indications J&J was promoting turns out to be obesity, according to the whistleblower who brought the case. Read the legal documents here [pdf format]. Thanks to Jim Edwards at BNET for posting these. Topiramate (the active ingredient in Topamax) is one of the two active ingredients in Vivus's experimental obesity drug Qnexa. But Vivus's formulation uses topiramate at a much lower dose than would be taken as a standalone...

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