The first installment of “The Asenapine Chronicles, by Salmon” may be found under the link in that title — and Salmon is, as ever, spot-on, again. Consider the vast sums invested — almost a quarter of a billion dollars — that Pfizer apparently abandoned, and simply walked on (detailed below).
Now, a cynical critic of big pharma might also observe that a company with a certain amount of “pliability” on moral, ethical and legal dimensions might — just might — be, in part, banking on the fact that nary a single putative-long-term asenapine patient (being mentally-ill to begin with) will be a particularly capable or believable witness in any ensuing litigation about drug safety or efficacy — if, in fact, it turns out to be unsafe, or unsound.
To such a company, what would matter most, would be how much Medicare/Medicaid (and the patch-work quilt of private health-plans) would be willing to reimburse for such a regimen — even if it is ultimately found to be unsafe — years after approval. But that, thus far, is merely a hypothetical scenario, as the candidate has not cleared FDA or EU authorities. Nor, I think, given Salmon’s analysis — is it ever likely to so clear.
. . . .Some other thoughts on Pfizer’s actions.
Pfizer dropped out of codeveloping asenapaine in late November 2006. As I’ve mentioned before Organon’s announcement of an accepted filing at Thanksgiving 2007 means that the NDA had to be submitted by early Oct 2007 at the latest or nearly 10 months after Pfizer dropped out of the deal. Since it takes about 9 months do analyses, write reports and to put together the documents for the submission. (even accounting for another couple of months so that both indications could be submitted simultaneously. This means that Pfizer dropped out after the Phase III studies were completed. Since there were 2 indications and both were submitted, and since the Phase II studies are presumably positive (otherwise the drug wouldn’t have gone forward) asenapine likely showed efficacy in at least 1 phase III study for each indication which in combo with a positive phase II study is usually sufficient for approval, even if one phase III study was negative.
N.B. there have been published abstracts from meetings regarding study results.
Also Pfizer paid $100 million up front and presumably some other milestone payment (total, if filed, was supposed to be ~$300 million.) Let’s assume a second $100 million milestone payment was made for a total of $200 million. In addition to this Pfizer likely conducted and paid for the US studies (assume 1 US study per indication per FDA’s usual requirements) with 3 or possibly 4 arms: placebo, active control and 1 or 2 dosages. If there’s 150 – 200 subjects per arm in a standard 6 week schizophrenia study and a standard 4 week bipolar study Plus a safety study at $7500/subject that’s another $15 million at least. So Pfizer likely dumped at least $225 million into this drug and then walked away after all the work was done. Even if this drug doesn’t work very well it still might mean several hundred million in sales per year anyway, which I don’t think even Pfizer would walk away from as every penny adds to the bottom line.
To me the total evidence available in press releases points to Pfizer dropping the drug because of a safety signal.
October 26, 2008 7:01 PM
Indeed — we shall see.