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
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.