http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist

“Indicates that the company apparently designed their studies to hide the relevant information” was your conclusion or the FDAs?

This is the FDA’s conclusion and comes directly from the asenapine review. Take a look at pages 897 and 986 from the PDAC briefing document that Condor sites.

“As a scientist I am sure you will appreciate the old adage that “extraordinary claims require extraordinary proof”.”

Agreed. However I am not prepared to go into the basis for my beliefs at this time or in this forum.

A”s a practicing medicinal chemist for 17 years, I disagree with your conclusion that theoretically expected but not reported metablites are evidence of a conspiracy. In preclinical research, I spent many years looking at this type of data, and metabolite prediction is much less of a science than I felt was implied in your post.”

I never claimed conspiracy and I agree that drug metabolite prediction is an inexact art and if I gave the impression that in general it was easy then forgive me. As you know I was talking about a specific group of compounds. When we have many years of experience with similar type molecules with similar pathways and the enzymes involved such as with the azepine antipsychotics then I believe we can have a fairly high confidence in being able to predict a couple of the primary pathways and the likely enzymes involved.

Salmon

That, I think, is what Salmon is referring to.

Pages 916 - 918 especially at bottom of 918

Summary of Patients who died. Causes and preponderance with asenapine compared to olanzapine. . . .

It appears in the middle of about 1,000 pages of background material submitted by FDA at the time of the Advisory Committe’s approval vote on asenapine, last year.

Nmaste

My comments were directed to the board as a whole, but also to:

“Technically almost every drug is marketed in violation of the law as the drug metabolism sections are clearly misleading and thus the drugs are misbranded.”

“There are of course other examples that I know of where companies and the FDA have hid that certain cancer drugs are metabolized differently by african americans so that not only are the drugs ineffective cancers but they are apparently much more likely to die from simply horrific drug reactions. The FDA has failed to mention anything in labeling even though there are other drugs that don’t have these problems because doing so would decrease sales for the companies by billions of dollars”

As a scientist I am sure you will appreciate the old adage that “extraordinary claims require extraordinary proof”.

As a practicing medicinal chemist for 17 years, I disagree with your conclusion that theoretically expected but not reported metablites are evidence of a conspiracy. In preclinical research, I spent many years looking at this type of data, and metabolite prediction is much less of a science than I felt was implied in your post.

I believe this is consistent with my original statement that an interaction would not suprise me. Considering when tamoxifen was developed with it being first marketed in the early 1980’s the sort of studies I indicate should normally be done in drug development would not have been applicable at that time. ~10 years or so later yes.

As for all information that was used to make the decision for the example I gave, I have to rely on the FDA reviews which indicates that the company apparently designed their studies to hide the relevant information.

Evidence that Tamoxifen is a prodrug that requires activation by CYP2D6 did not begin to really solidify until the last 12 months or so.

There is an old adage about not attributing to evil anything that can be explained by stupidity. To which I would add that one should be careful about attributing decisions to stupidity unless you have all information that was used to make the decision.