One of the less appealing ways that companies have tried to fill their drug portfolios over the years has been to look through their current drugs in search of one with a main active metabolite. That altered structure then becomes a clinical candidate for the next generation. I’ve said bad things before about Clarinex (desloratadine), son of Claritin (loratadine), the most famous example of this practice. That “des” prefix tells you that the newer drug is just the older one minus some part of its structure, in this case, minus a carbamate group that the liver clips off anyway. Even non-chemists can see the change, looking at the top parts of the structures in those Wikipedia articles.
Now comes Pristiq (desvenlafaxine), spawn of Effexor (you guessed it, venlafaxine). This one's also a simple metabolic change, OH from O-methyl. Wyeth has done very well with Effexor over the last few years, and they’re not ready to give up on that market share once it goes off patent this year. The timing of this new drug is, as they say, no coincidence. The Carlat Psychiatry Blog, not a place to go to find lots of warm feelings for the drug industry, has its “Top Five Reasons to Forget About Pristiq”. From the way things look, I have to agree with them; at the moment it’s hard to see much need for the stuff.
But there’s a good point made there by an investigator on the clinical trials, Dr. Michael Liebowitz of Columbia. He, quite reasonably, is waiting for the market to settle whether the drug is of any use or not: “If it is useful, then it will make money for the company, and if it is not, it won’t.” Update: there's more from Liebowitz on this topic, and on follow-on CNS drugs in general.
Exactly. I’m very much in favor of letting drugs stand or fall on their merits, if any. My first guess is that Pristiq is not much of an addition to the pharmacopeia – and if it isn’t, Wyeth deserves to lose the money they’ve put into it, since that, frankly, would have been the presumption from very early in the drug’s development. They took this drug forward at their own risk, and should profit or lose by it accordingly.
One thing I’ll say for the company, though: they actually seem to be running a head-to-head study between the two drugs. That’s good to see, and it’ll be quite interesting to see what case Wyeth can make, if any, after the data come in. At least they’re not just banging on tin cans and shouting “Now with the great taste of fish!” or something. Interestingly, as a comment on the Carlat blog points out, the company has already published data on one unimpressive trial with Pristiq, and I have to thank them for doing that, too. If there was ever a head-to-head efficacy study run between Claritin and Clarinex, I definitely missed it – I’m willing to be corrected, of course, but I’m pretty sure that there never was one).
So one-and-a-half cheers for Wyeth. I wish, in most cases, that companies would avoid the metabolite-drug idea. Alternatively, I wish that everyone’s drug pipeline was well stocked enough that such follow-ups didn’t look financially appealing. But if you’re going to have them, taking an honest look at their benefits is the only way to go.