Salmon is on FIRE! — More of the Asenapine Chronicles

And, per Salmon’s closing lament, below, we may widen our topics a bit, here — in the very near future. . . . So do stay tuned!

. . . .I checked some of AZ, Org, and SP press releases and there were 4 acute schizophrenia studies (2 reported as positive and 1 as failed (i.e. neither asenapine nor the active control olanzapine, (Zyprexa), worked), thus the other study was negative (i.e. the active control worked but asenapine didn’t). In addition there were 2 positive bipolar studies, and based on the reported results they appear robust in bipolar at least.

So even if the efficacy of asenapine in schizophrenia was so-so or even insufficient for approval, the reported evidence for bipolar appears adequate for approval. So it’s puzzling why at least one indication wasn’t approved or at least approvable.

However remember that at about the same time FDA changed their policy so as to no longer have approvable letters, only approval and nonapproval. This would make the real reasons for nonapproval more opaque.

Plus the acute schizophrenia study reported in the press release this week appears to be the same study reported at the APA meeting May 8th. Yet both the May and recent SP press releases said the safety results would be released later, (hmmmm).

Besides lack of efficacy, or clinical safety issues, there could be manufacturing issues or animal toxicology issues that might hold up approval. But these more typically result in approvable letters and not simply nothing.

Prior to negotiations for PDUFA IV pharma was making a lot of noise to get approvals right at the end of the PDUFA review period and no more approvable letters.

Also during the negotiations for PDUFA IV PhRMA was pushing to get the FDA to shorten the review clock to 8 months. This wouldn’t fly but in a draft of PDUFA IV the as outlined in the bills for Food Drug and Administration Act of 2007, they did get that labeling negotiations would begin 60 days before the PDUFA due date if it was to be approved or approvable. Yet in the final version of PDUFA IV as outlined in the FDAAA 2007 this isn’t specified but instead it refers you to a MOU. (Nice way to hide what’s really going on.)

FDA regs indicate that going beyond the PDUFA due date can only be done if there is an agreement with the sponsor. Plus extensions to the due date are not to be done for major amendments (such as more data), and manufacturing issues etc. are now supposed to be taken care of by early communications during the review cycle so FDA can give an answer one way or the other at 10 months.

It is now over 1 year since filing. SP had to have known at least 5 months ago (around May when they first reported on this new long term efficacy study) if they were going to get an approval or approvable, and they could infer a nonapproval even before they would hear officially. They then would have had to make an agreement with FDA to extend the review clock. Another interesting clue is Fred Hassan’s rant on the front page of the Wall Street Journal on June 30th, saying he doesn’t know how to get something past the FDA. Which is shortly after when he should have known what the results of the review were.

So we should have then heard news about approval at around the time of the 2nd Qtr report or shortly thereafter. But instead we only heard more bad news about Vytorin, i.e. Cancer. If they thought it was never going to be an approval SP would have withdrawn the application quietly and we would never hear anything. However the fact that they’re still reporting positive studies and that they’re long term suggests that there’s an agreement with FDA to extend the review for some reason, and that these new studies will provide some additional safety information. (Even though regulations don’t allow this.) All this suggests to me that Fred himself is withholding material information that would have sent the stock price even lower than it did go, and it may even suggest FDA involvement.

However even if the new data is a 6 month study it doesn’t mean that people are on the drug for 6 months. (In the labeling for positive studies for other antipsychotic drugs for the same indication the average length of time on the drug until relapse was ~ 50 days and even though this was statistically different from placebo it was only about a week longer, which is so small it may not be clinically significant.

As you can see based on the way the new FDAAA 2007 law is set up, companies will know the results of whether a drug is to be approved or not 2 months before the public. This gives a lot of room for insider trading or other manipulations, including collusion with FDA officials. I followed this law closely and if you know how the process works it’s virtually everything that Pharma could possibly want but you really need to know the process to know how to have written this law, which would require a lot of input from Pharma (i.e. Pharma virtually writing the law.)

That leads me to another interesting observation. The FDAAA 2007 is known as the Kennedy – Enzi bill. It just so happens that Ted Kennedy’s son runs a consulting firm for Pharma called the Marwood Group. I’ve really got to wonder what sort of expertise Ted Kennedy Jr. has that he could be a consultant to Pharma (in addition to investors). ( Also Sen Kennedy has just been reported to be actively working on health care and expanded access and we know that this will help Pharma, especially those extremely profitable antipsychotics whose off label use and indications have been expanding and expanding. Just look at Seroquel XR (quetiapine) and all the new indications under study. Not to be partisan let’s not forget Bush and his interest in expanded mental health screening programs for children.

Now the same day as Fred’s rant on the front page of the WSJ (June 30th), Janet Woodcock’s (the head of the center for drugs) Public Calendar shows she had a meeting with Ted Jr. of the Marwood group, ( Boy are there a lot of coincidences. As a speaker I have to wonder what clients would have been invited, and what would have she said that could be so interesting to Pharma and investors, and who would have paid for her travel expenses to NYC? Remember Congress has been looking into inappropriate meetings and communications between Sr. FDA officials and Pharma. Even if FDA paid is it really appropriate for the head of the FDA’s drug division to have a private meeting and discussion with investors and Pharma consultants that the rest of the investing public doesn’t have access to?

There’s a lot more interesting stuff both on the limitations of efficacy as well as likely toxicities for asenapine and similar drugs that can be inferred by examining the literature and summary basis of approvals that aren’t generally appreciated. This would be standard practice for any company to do. Plus Organon has been working on structures similar to asenapine since the 1960’s. So they would know a great deal about toxicities. You’ve also got to ask yourself if they’ve been working on these structures since the 1960’s why have so few come to market and why have they taken so long and why do they keep working on them.

It’s too bad you only post on SP, they’re not the only company whose drugs I follow.

— Salmon

October 27, 2008 11:22 AM

We may have to do something about that. And soon.

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