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Biotech / Medical : ACADIA Pharmaceuticals Inc (ACAD) -- Ignore unavailable to you. Want to Upgrade?

To: NeuroInvestment who wrote (374)	1/12/2007 4:58:55 AM
From: mopgcw	Read Replies (1) \| Respond to of 588

Harry, Appreciate the insight -- if I could impose on you to share your opinion on Lehman's take: "We believe that a single case of mild leukopenia in recently reported phase II results for ACP-104 should be of limited concern given what appears to be an atypical profile relative to that seen with Clozapine. In particular we would suggest that the transient nature of leukopenia in this case is unlike the progressive leukopenia seen with clozapine, that the early onset is atypical of the later onset typically seen with Clozapine, that the rapid resolution of effect on drug discontinuation is also atypical and that a preceding fever and investigator determination of lack of drug causality should provide further reassurance. We would note that leukopenia is seen with other drugs not associated with agranulocytosis including Risperdal, Zyprexa, Haldol, Seroquel, Geodon, Abilify, Symbyax, Lunesta, Ambien, Sonata, Prozac, Effexor, Zoloft, Cymbalta, Wellbutrin, Celexa, Compazine, Thorazine, and Mellaril. While a lack of certainty on the exact mechanism underlying Clozapine induced agranulocytosis makes it difficult to completely rule out the possibility of similar effect with a major clozapine metabolite we would suggest several published theories that could lend support to a lack of effect with ACP-104. In particular, we would point to: 1) A publication by Uetrecht et al in 1997 suggesting that clozapine analogues with a nitrogen bridge between 2 aromatic rings are oxidized to a reactive intermediate that causes agranulocytosis. In this study nitrogen-bridge containing analogues formed such reactive intermediates while there was no evidence of reactive intermediates with oxygen- or sulfur- bridge containing analogues. We would note that ACP-104 does not contain a nitrogen bridge. 2) A more recent publication by Ostrousky et al in 2003 suggesting intracellular generation of nitrenium ion associated with depletion of intracellular glutathione and sensitivity to oxidative stress. In this study the authors suggest that decrease in NQ02 gene expression has been found in patients with agranulcytosis and NQ02 is thought to be protective against oxidative stress. We would note that ACP-104 is less lipophyllic and as such penetrates cell membranes less well." mucho gracias. george