The irrepressible PM (over at Gooznews.com) strikes again, this morning -- the author has posited an intriguing "mechanism of action" theory to explain why the SEAS cancer data may not be an anomaly at all, among other matters. It involves plant sterols. 
Trust me, you'll want to read this -- this one post may well cause "serious, open minded scientists" to rethink what Schering-Plough is claiming, related to the SEAS cancer data. Here's a bit of it:
. . . .The trial -- known as the SEAS trial -- was an effort to show the combination pill reduced heart disease. Ezetimibe is unique in that it inhibits cholesterol absorption (as opposed to removing cholesterol from the blood like statins). But ezetimibe also inhibits absorption of dietary plant sterols, and one plausible theory is that the reduction in sterol absorption in the patients in the SEAS trial may have increased their risk of contracting cancer. . . .
Excellent.
5 comments:
I'm so glad you're talking about mechanisms.
I won't talk about Vytorin and CA, but I do want to discuss a little bit about boceprivir.
This weekend I was thinking that for several different companies to all come up with structurally similar drugs for Hep C around the same time means that they all have a common mechanism that they're basing it on and the it must involve the part of the structure that's similar across molecules.
Then it struck me. Zyprexa, Lilly's wonder drug and that favorite of prosecutors and personal injury lawyers everywhere was noted to not only cause weight gain and diabetes in the original summary basis of approval. But it also caused severe liver toxicity in several people who were Hep C positive and structurally it has a metabolite that's very structurally similar to boceprevir and the other ...previr's. Not only that but there's a lot of information in the scientific literature that points to the same thing. In fact after Zyprexa, drug companies and FDA only started using people with non Hepatitis induced liver disease (e.g. alcoholic cirrhosis only) in hepatic impairment studies with new drugs and also began screening Hep C patients out of clinical trials.
I would absolutely bet my house that someone in FDA knows something about this and has been helping drug companies cover this up for the last 12 years or so.
The information is right there on the FDA's website. All anyone needs to do is look at the original reviews for Zyprexa and look at the metabolism of the quaternary Nitrogen. (In case anyone's interested just google Drugs@FDA.)
Looks like another good reason against preemption.
Lawyers start downloading now because when FDA reads this comment those those files probably won't be there anymore.
Salmon
Thanks for this, Salmon! I'll look into it. . .
Do take a look at comment number 8 in the "Trivial Pursuit" post, below! I'd be happy to handle the delivery in any of the mentioned ways. . . .
Cheers!
I saw some interesting articles today, about the effects of various statins on Isoprenoid metabolism and the stimulation of
G1 phase cell cycle growth.
It appears that Peter Honig at Merck has been involved in this and as well as a number of people in ASCPT and it goes back a number of years. Say aren't there a lot of FDA people who are quite involved in ASCPT? I bet you guys have been talking haven't you?
It might be that SP-Merck thought Vytorin might actually decrease CA, but they may have gotten burnt by slight differences in intercellular pathways or not counting on a metabolite that has the opposite effect.
These things also seem to tie into arachadonic acid metabolism (think Vioxx) and cell growth and fibrosis (think hepatotox and Trovan) and cardiac tox (moxifloxacin and phen-fen) and hepatic fibrosis and connective tissue toxicity (moxifloxacin).
Fred those G-coupled proteins and that systems biology sure are a B.. ain't they.
Salmon
Condor,
You know I love changing the topic. So here goes. I'd like to go back to Scherings recent Q-10 filing and a recent post in cafepharma saying asenapine was going to save the day.
Let's do a little math:
Monday Nov 26 2007 Schering announces asenapine is filed now since this is the monday after Thanksgiving I bet that the letter had to be received at least on Tuesday Nov 20th if not earlier.
Now the filing meeting is 45 days after submission and the letter to Schering has to go out by day 74 that means that even if Schering made the announcement the same day, the submission date likely was between Sep 12 and Oct 12 2007 and possibly earlier if they sat on it. Meaning the PDUFA due date is today at the latest and at least as early as July 12th, and possibly even earlier. (Now if I were that close I sure would try to make the filling a little earlier so the approval would be prior to the end of the quarter)
So why haven't we heard anything about the approval?
Well yesterday was the implementation of FDA's final rule for no longer giving approvable letters. If you look at the final rule it was signed on June 26th (from the Assoc Commish) and placed in the Federal Register on July 10th. Now a final rule is only supposed to be issued when no outcry is expected and there sure has been a lot of outcry with this.
So if we haven't heard anything, this means that either SP submitted a major amendment (not good) that extended the review clock or they actually had to enter into a formal agreement with FDA to extend the review clock (also not good). However what's really funny is this all coincides with this new final rule on complete response letters. Now since we haven't heard anything we need to assume that asenapine will get a complete response letter. But if they do we'll no longer be able to tell if it's a big fat no way will you ever get an approval or something less.
Now if the letter had come earlier when it appears that it should have and it was really bad peice of news then the stock price would have dropped like crazy at the exact same time as the 15% stock price drop due to the Vytorin cancers.
It seems to me that something's rotten in Denmark and it looks like the FDA commissioner's office is involved.
Salmon
Aug 13 11:30 AM
Looks like and interesting morning for SP stock trades. Even though it's holding steady it's up and down and the down movements are nice drops all at once with the largest volume trades. The ups are small and take some time and then WHAM! somebody looks like they're taking some profits.
What do they know?
Salmon
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