Before some of you that read these message boards start putting your hard earned money in EPCT here is why Ceplene WILL be rejected by the EMEA:
-No study in people aged 20-50, the EMEA will definitely ask for that study before they will consider approval.
-A single 320 patient study is not enough.
-Ceplene was designed for skin cancer and failed in p3 studies.
-No statistical significance in overall survival.
-just because there is no treatment for relapsed aml the emea is just like the fda, don´t count on any sympathy.
Folks, do yourself a favour and put your money in somthing else and don´t listen to the pumpers on this board.
See you at 60 cents.
yes, agreed. you would think that with this type of approval right, if they follow the standard, given the benefits outweighing the risks here, that there would have to have been something fundamentally wrong with some aspect of the test that would call the entire results into question, in order for it to be negative. all IMHO
how many times has jack said the phrase "unmet medical need"?????
this gives them the ability to not reject based upon test size etc, allows them to save face and get the drug to the patients with out jeopardizing their proceedural process.
A good option IMHO
didn't find the actual guidelines, but did find this explanation on the emea website:
Sometimes, the CHMP recommends that a medicine be given ‘conditional approval’. This happens when the Committee has based its positive opinion on data which, while not yet comprehensive, indicate that the medicine’s benefits outweigh its risks.
The company is given obligations to fulfil, such as the performance of further studies. The approval is renewed on a yearly basis until all obligations have been fulfilled, and is then converted from a conditional approval into a normal approval. Conditional approvals can only be granted for medicines that satisfy an ‘unmet medical need’, meaning the medicine is intended to be used for a disease or condition for which no treatment is readily available, and it is therefore important that patients have early access to the medicine concerned.
Medicines that have been granted conditional approval are identified on this website with the symbol .
also, found this presentation, but this seems to be prior to the issuance of the guidelines...
http://www.fda.gov/ohrms/dockets/AC/05/slides/2005-4191S1_03_FDA-Pignatti.ppt#257,1,EMEA current thinking on Conditional Marketing Authorization
Anyone in this board wrote: "Changed primary endpoints in middle of the study. That could have affected the outcome">
You can principally not affect a survival rate or a quality of life result by technical modalities - simply a misleading rumor mixed with medical nonsense
Fair enough, but you made it sound like a whole other story when you pointed the OS out. Told us about the lack of results here when the study was not powered to show that. Why did you bring that up when it wasn´t inculded in primary endpoints? And moreover, the comments about the population (age factor). I don´t like that misleading thing of yours. With a strong sell rating I guess it´s in your agenda, huh?
Anyway, thanks for the response.
From the article in blood:
" In the initial protocol there were 2 primary endpoints; one for patients in CR1 and one for patients in subsequent CR. However, when a total of 320 subjects (261 in CR1 and 59 in CR > 1) had been enrolled, accrual of the necessary number of subjects in subsequent CR did not seem to be feasible. Therefore, further recruitment was terminated in October 2000, and in a protocol amendment the primary endpoint was changed to determination of LFS in the combined population of patients in CR1 and in subsequent CR (ie, all patients randomly assigned into the trial)."
It's called a phase 4 study (the EMEA may call it something else), you'll have to research your questions, please let me know what you find. I do not think it is that uncommon when the agency is trying to get an unmet medical need satisfied.
Do your DD before writing, please. You are wrong on many of the most fundamental factors. Enrollment critery when it come to age was 18 years. 320 patients with AML (median age, 57 years, range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1).
About OS: Primary endpoint was not OS. Study was not powered to meet that criteria, still at 5 years they nearly meet 0.05 for survival. Impressive. Primary endpoint was prolonging the leukemia free survival in patients with acute myeloid leukemia in first or subsequent complete remission (CR) following consolidation therapy. Label for NDA with EMEA is CR1. Data very robust here. Read journal Blood where results have been published.
One more thing:
"just because there is no treatment for relapsed aml the emea is just like the fda, don´t count on any sympathy" (your comment)
Says it all. Do your DD before speaking. Ob you do not understand what this is all about...
You forgot to address this one:
"A single 320 patient study is not enough."
Liten to the December 12 webcast, Jack addresses this concern
The MAA for Ceplene adequately meets the CHMP guidance for a positive opinion based upon a single pivitol study.
Several drugs approved in similar fashion were Gleevec and Proleukin.
Also, post hoc OVERALL SURVIVAL at 5 years reached statistical significance p=.036 when hematologic deaths were censored from the study (older population, non related deaths).
Additional even more compelling data has been revealed and submitted to the EMEA since the MAA application in 2006.
add'l IL2 studies (2,000 patients studied no effect on AML and
5 year post hoc analysis with and without hematologic deaths presented at the REQUEST of the EMEA.
All of the above IMHO
excellent post, bio...
i have a question for you -- in you opinion, what are the main open issues that could result in ceplene receiving a negative opinion? i'm very interested in what you think.
for me, the single biggest issue is whether the emea will fully-accept the data from the eight il-2 only published studies that show that il-2 alone does not work. we all know that the reason why the fda wouldn't allow epct to file in the u.s. was because the epct study didn't demonstrate this. however, since that time, there have been major studies published by third-parties which demonstrate this. i have no idea whether and to what degree the emea can rely on third-party data. what is clear to me is that if the emea wasn't willing to even consider the third-party data, then it wouldn't have permitted the filing either. further, if the emea was having a major issue with the third-party data, then you would think that the company would be a little more reserved in its remarks about how encouraged they are about the prospects for approvability. all this leads me to think that the emea is going to fully-accept the third party data. i could be very wrong, however.
what are your thoughts?