Targacept and TC-5619

Targacept and TC-5619: It seems eons ago that Targacept was riding high on the wings of its TC-5214 partnership with AstraZeneca. We had hoped that their nicotinic alpha 7 entrant, TC-5619, would put them back on track, but the Phase IIb trial in schizophrenia failed on all counts.  The question that arises now is whether this means that the molecule truly has no value. As was noted in last month’s NeuroPerspective, we had been hearing concerns that TC-5619’s admirable potency might backfire, missing the  sweet spot on the U-shaped curve that appears to characterize the nicotinic alpha 7 receptor system’s malleability.  This trial was dosed at 5mg and 50mg levels, compared to .3 and 1mg dosing for EnVivo‘s drug in the same population, thus Targacept may have overshot the mark considerably (AbbVie does not disclose the dosing for ABT-126, its nicotinic alpha 7 candidate). Given the success of EnVivo’s nicotinic alpha 7 entrant in the same population, we  believe that this was more likely a failure of the trial than of the molecule. It also would be of interest to look at clinical site performance parsed out by geography, since psychiatric trials have been particularly vulnerable to the vagaries of site selection and performance.

To some degree it is a moot point, Targacept’s CEO has terminated development of TC-5619 in both schizophrenia and Alzheimer’s. But for a CNS company that is looking for an asset addressing cognition in these areas, TC-5619 might well be worth the effort to more clearly define its optimal dosing. While it may be necessary for the dust to settle at Targacept, a conversation regarding the possibility of licensing TC-5619 would be worth having.

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One Response to Targacept and TC-5619

  1. David A Katza says:

    People in our field keep making the same mistake – trying to prove concept without understanding the pharmacology of the tested dose(s).

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