tag:blogger.com,1999:blog-4241416962008169508.post1763430632957194526..comments2024-03-17T09:40:53.611-04:00Comments on Just A Life Sciences Blog...: Salmon Rises -- On Post-FDA-Approval Saphris Presser, of Yesterday. . . .Unknownnoreply@blogger.comBlogger5125tag:blogger.com,1999:blog-4241416962008169508.post-64001782641739998492010-01-21T16:51:34.445-05:002010-01-21T16:51:34.445-05:00BTW, use GPS blocker to jam all spy devices in you...BTW, use <a href="http://www.tayx.co.uk/" rel="nofollow">GPS blocker</a> to jam all spy devices in your room or office.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-4241416962008169508.post-48960239748623623432009-11-17T17:58:18.494-05:002009-11-17T17:58:18.494-05:00It is rather interesting for me to read that post....It is rather interesting for me to read that post. Thanx for it. I like such topics and everything connected to this matter. I definitely want to read more soon.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-4241416962008169508.post-26401424121806834562009-09-16T15:23:35.598-04:002009-09-16T15:23:35.598-04:00I forgot. With Iloperidone the higher dose was sho...I forgot. With Iloperidone the higher dose was showing efficacy because of the MMRM analysis with likely excluded subjects whose psychosis were worsened by iloperidone. So the higher dose may have only been effective in some people and that's why the average response tends to be less than the active control.<br /><br />SalmonAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-4241416962008169508.post-51714932338741069072009-09-16T15:18:15.535-04:002009-09-16T15:18:15.535-04:00OK, now that I've given you some time with thi...OK, now that I've given you some time with this one I want to comment on something that I wrote intentionally.<br /><br />"Now on top of all this the dose is up to double the approved dose so assuming there’s a dose response and since the approved dose is 5 mg, this is another factor that doesn’t reflect the population that asenapine will actually be used in."<br /><br />In truth the data does not reflect a montonic dose response in schizophrenia (Thank you for providing a graphic). This might be due to variability or to a metabolite that worsens the illness in some people as the dose increases. In addition when these sort of studies are done mean or median final doses are reported so the mean dose may be around 6 or 7 mg.<br /><br />In the marketplace however physicians may be pushed by sales reps to go up on the dose (especially if there is a cost differential in favor or Schmerck).<br /><br />However the toxicity or AE profile in the labeling is determined at the 5 mg dose or long term at only a slightly higher dose and relatively healthy patients are used who typically don't reflect the population drugs are used in.<br /><br />Thus not only is the study rigged as to efficay it's likely rigged as to the toxicity profile also.<br /><br />If you look at the Iloperidone reviews. The study that FDA eventually used as a second positive study to approve it was not the study the sponsor wanted to use. Instead the FDA used a study so they could say the regulatory requirements for long term toxicity had been met (500 subjects for 6 months and 100 for 1 year) for if they had used the study at the likely efficatious dose of > 20 mg they still wouldn't have had sufficient patients to meet the regulatory requirements for safety data and another study would have been required anyway.<br /><br />This way not only don't we have adequate human safety data with Iloperidone but possibly ineffective doses may be in the labeling if it were to eventually turn out to be effective at the higher dosages. In any case the animal and human safety data with iloperidone in my opinion strongly argues against approval.<br /><br />Salmon<br /><br />SalmonAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-4241416962008169508.post-84615231989283443612009-09-15T12:46:35.131-04:002009-09-15T12:46:35.131-04:00My mistake.
It was the tertiary pharm/tox review ...My mistake.<br /><br />It was the tertiary pharm/tox review (part 3 page 56/61) on July 22nd, 2008 that indicates it's due to direct effects of the drug and not primarily the effects on the dams.<br /><br />When you look at reproductive study after reproductive study in the pharm/tox reviews they're dose dependent and it's clear they're direct effects and not secondary effects on maternal toxicity. Plus there's dilation of the heart ventricles in the pups. (Hmmm!)<br /><br />What's noteworthy is that the medical reviewer (page 12 of her review page 13 of the pdf file) notes that she had not been provided with a final version or a draft of the pharm/tox review yet and had previously been assured by the pharm/tox reviewer that there were no unexpected findings. (7/1/2008 Noon)<br /><br />However the pharm/tox review is signed off by both the reviewer and the supervisor on 6/30/2008 between 4 - 5 PM.<br /><br />I checked with a source inside the FDA and asked how this could be.<br /><br />I was told that due to the even shortened PDUFA deadlines that reviews are now done simultaneously and thus reviews that are dependent on other review diciplines can't get the appropriate preliminary information in a timely fashion to guide them and that this appears to have been deliberately incorporated into the new review processes that were implemented last year. In addition when they know that a reviewer will question someone elses conclusions when they're suspect they may hold off on providing the relevant precursor review until the dependent reviewer is finished or even revise the precursor review afterwards in order to dismiss opinions.<br /><br />As for the timing and the medical reviewer not knowing of the other reviews completion. This may happen as the reviews are secondarily reviewed then given back for minor changes and then the reviewer is told to put them into the database prior with the precursor review going in shortly afterwards(without notification).(Unexpected delays can mess up the sequence.) This is especially common when reviewers are up against PDUFA deadlines and are simultaneously being run in circles by FDA management so that the reviewer will not check other things when they don't want the reviewer to be aware of these other things.<br /><br />SalmonAnonymousnoreply@blogger.com