Merck Buries Taranabant: Farewell Cannabinoid Antagonist Field

Merck (MRK) has taken a step that many people have been expecting, and announced that they are no longer developing taranabant, their cannabinoid antagonist (or is it an inverse agonist?).

I'd expressed grave doubts about the drug earlier this year, which turned out to be well-founded. That latter post included the line "I don't see how they can get this compound through the FDA", and now Merck seems to have come to the same conclusion. Further clinical data seem to have shown far too many psychiatric side effects (anxiety, depression, and so on), which increased along with the dose of the drug.

The cannabinoid antagonist field has already experienced a crisis of confidence after Sanofi-Aventis's (SNY) rimonabant failed to gain approval in the US. This latest news should ensure that no company tries to develop one of these drugs until we've learned a great deal more about their pharmacology. Given how little we know about the mechanisms of these mental processes, though, that could take a long, long time. We can pull the curtain over this area, I think.

Comments

[Tony101:]

Something Arena pharma investors love to hear.

2008 Oct 02 11:03 PM

[V. Di Marzo:]

Taranabant is, pharmacologically speaking, not exactly the same thing as rimonabant (Acomplia). It has an at least 10-fold higher affinity for cannabinoid CB1 receptors, which might have prevented the developers from finding a useful therapeutic window for the dose (from the disclosed data, 2 mg was safe but almost inefficacious, whereas 4 mg was efficacious but less safe than rimonabant 20 mg). Furthermore, Merck have always claimed that this compound is more of an inverse agonist than rimonabant, rather than an antagonist, which theoretically should increase side effects (agonists act more independently from the state of the endogenous system they interact with than antagonists). Ergo, I think that rimonabant (for which the "half-dosage" has not been tested yet in the clinic) still stands good chances to be used safely (and, indeed, it seems to be, at least in over 50 countries all over the world). Furthermore, we still don't know about the results of the phase III trials of Pfizer's CB1 antagonist, Otenabant. Still too early to pull any curtain over this area, in my opinion....

2008 Oct 03 05:59 PM

[D. Linsenbardt:]

Today Pfizer announced that they pulled out of phase III clinical trials for their CB1 antagonist due to "a changing regulatory environment"...

I wonder if there is public access various aspects of the pharmacology of these compounds... (i.e. comparisons to Rimonabant)

2008 Nov 05 05:29 PM