UPDATED 10.27.08 -- Do go read Part Three of the Continuing Asenapine Chronicles. Follow the link.
In comments, earlier, Salmon laid out some fascinating inferences from the Schering Asenapine press release of yesterday. They deserve a much-wider audience -- thanks, Salmon!
Do take a look:
. . . .Asenapine was filed over a year ago. It should have been approved already, yet nothing has been announced. When you have an add-on a study like this -- with no news on an approval and safety data to come out at a later time -- it points to major safety issues with a drug.Since structurally similar compounds with major safety issues are marketed i.e., Zyprexa and even Clozapine with restricted access, this points to potentially huge safety issues. [Is this] another study carefully-designed with exclusion of certain subjects (e.g. bipolar) that may be intended to dilute out and obfuscate serious adverse effects[?]. . . .
[Later. . . . Do click on the image, at right, to view full size.] For what it's worth -- this study appears to be the same as the one the results were reported on, towards the end of last May or early June. If that's the case, then SP should have already had more than enough time to complete their analysis of safety data and to submit the results during the present review cycle. If there is a safety issue especially in bipolar this study would dilute the overall incidence rates.
I looked at SP's press release, and it was a 6 month placebo controlled study in 700 people at doses of 5 mg and 10 mg with only about 380 people on asenapine with some sort of run-in period -- that made no sense -- and may indicate they were screening out people (e.g., who switched meds from an active control during acute treatment), and either lost efficacy, or then had toxicities on asenapine.
If half the people on asenapine received 5 mg and half 10 mg then only about 165 people got the higher dose. Based on this, you can't even be guaranteed to see even a single case of a serious dose related toxicity [if that outcome were to occur] in 1% of people. Plus, this says nothing of cumulative toxicites, that show up after 6 months. Since there's no active comparator (the most obvious would be Zyprexa) you can't even tell if it's less safe than Zyprexa -- which is likely also intentional.
Overall, things look very fishy.
-- Salmon
Quite well-reasoned, and yes, indeed, they do. . . . Again, thanks for taking the time to share your expertise, and practiced perspective, here, Salmon!
Even later (in commentary, below), Salmon has this to offer:
There are other things that are suspicious about this program. For example this drug has been in development for decades. It simply doesn't take that long to do 4 - 6 week acute efficacy studies in an illness that's common and for which it's easy to show efficacy. (Preclinical prior to human studies only takes 2-3 years max.)This suggests that there were either safety or efficacy problems(or both) noted a long long time ago.
Pfizer also dropped codevelopment of the compound which was proposed to bring in over $2 billion/year.
The fact that we haven't heard anything in the last 2 - 3 months when we expect to hear at least something and we've got additional bad news with Vytorin during the same timeframe suggests that SP doesn't want to release any more bad news at the same time and drive the stock price even lower. (Looks like withholding of material facts to me.)
Plus maybe you can comment on this, but it this were such a great drug why wouldn't Azko Nobel simply take Organon public like they planned rather than sell it outright to SP. Looks like AN simply took the money and washed their hands of a dud with problems.
-- Salmon
October 24, 2008 4:27 PM
[My thoughts on Salmon's last paragraph, immediately above, are now in these comment-streams.]
Subsequently, an anonymous commenter just offered an echoing concern -- and an excellent observation:
I agree with Salmon. There is something 'amiss' here.
Why did Pfizer pass on this? You could say Azko didn't move on their own as they wanted to rid themselves of pharmaceuticals -- to concentrate more on chemicals. But Pfizer passing. . . . must be something wrong.
October 24, 2008 5:57 PM
5 comments:
There are other things that are suspicious about this program. For example this drug has been in development for decades. It simply doesn't take that long to do 4 - 6 week acute efficacy studies in an illness that's common and for which it's easy to show efficacy. (Preclinical prior to human studies only takes 2-3 years max.)This suggests that there were either safety or efficacy problems(or both) noted a long long time ago.
Pfizer also dropped codevelopment of the compound which was proposed to bring in over $2 billion/year.
The fact that we haven't heard anything in the last 2 - 3 months when we expect to hear at least something and we've got additional bad news with Vytorin during the same timeframe suggests that SP doesn't want to release any more bad news at the same time and drive the stock price even lower. (Looks like withholding of material facts to me.)
Plus maybe you can comment on this, but it this were such a great drug why wouldn't Azko Nobel simply take Organon public like they planned rather than sell it outright to SP. Looks like AN simply took the money and washed their hands of a dud with problems.
Salmon
I agree with Salmon. There is something 'amiss' here.
Why did Pfizer pass on this? You could say Azko didn't move on their own as they wanted to rid themselves of pharmaceuticals-to concentrate more on chemicals. But Pfizer passing...must be something wrong.
Great stuff, here -- me?
I am just watching -- and learning, from these wise ones.
To stay busy, though, I did just "bake-up" a glossy-photoshopped jpeg graphic (of the chemical structure of the drug candidate at issue) -- enjoy, above.
Namaste
As to the "why" on Schering's Organon purchase -- my own personal financial analysis would suggest that CEO Hassan overpaid -- and ended up paying much MORE than even an IPO of the spun-off Organon businesses alone would have ever fetched. [Melissa Davis of the Street wrote essentially this, over this past summer.]
Let's face it -- the whole Organon deal looks like a deal of desperation -- Hassan and crew knew they'd need a "hole" to bury coming "restructuring and streamlining" charges in -- and Organon was it. It would be a convenient excuse -- and it would generate some cash-flow, to partially cover the coming swoon of Vytorin.
At that point, the price they were willing to pay became a mere afterthought -- especially if one posits that Hassan and crew actually knew there would be "no good news" from ENHANCE -- by the Summer of 2007.
And all of that seems highly-likely, given what Senator Grassley (via his staff, more accurately) has been able to piece together, since then.
So -- yes -- I think there were real reasons why Pfizer passed on it, and why Organon didn't get sold in a public offering.
This too will likely lead to a flurry of lawsuits, as time wears on -- and the more complete truth, outs.
Thanks!
Thank you Condor and Anonymous.
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.
Salmon
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