FINALLY, they clarified the CURRENT interpretation of numbers, publically & in writing.

In their 2008 4th Quarter presentation, filed today by way of a 8-K form, here is their breakdown:



http://www.sec.gov/Archives/edgar/da...1biexv99w1.htm

So, the new total of 10,700 (for those who have been on 18+ months now), does not include people from the trials PRE-Nov, 2004. If I remember correctly, Tysabri was brought back (fast-tracked) onto the market about that time, and in about Mar/05 was pulled because of the 3 cases of PML that were discovered. (I would presume that those 3 cases were part of the 4700 trial patients from pre-Nov/04 though . . . even though the ratio of 1:1000 was based on 3:3000 (not 4700) trial participants ...).

Either way, this would seem to indicate the current ratio for PML is 7:18,200 (10,700 + 4300 + 1800 +1400), or 1:2600 . . . bearing in mind we don't know how many are potentially being confirmed for PML at the moment. Additionally, per their 3rd quarter Q&A response, we will likely never know how many "suspected" (unable to "confirm" & just taken off ) cases there have been along the way . . .

"Operator:
Your next question from the line of Jim Birchenough with Barclays Capital.

Jim Birchenough - Barclays Capital:
Yes, hi guys. Just following up on TYSABRI trends. I'm just wondering since the two reported cases in Europe, have you've seen any uptick in trends for suspected cases, whether any patients have been plasmapherese in the U.S. and just whether plasmapheresis itself increases the risk for immune re-constitution syndrome? Thanks.

Unidentified Company Representative:
Well we're not going to comment on suspected cases. To remind you that our clinical vigilance and risk management plan requires people to be highly vigilant for TYSABRI and if they cannot exclude PML, they are meant to stop TYSABRI.

So, we expect a lot of people to be stopping TYSABRI if they can't rule out PML. And we like to see that that happens... And in terms of plasma exchange, as Cecil noted, it is in the label whether or not it increases IRIS. We've known for a long time that immune re-constitution increases IRIS. Its called the immune re-constitution inflammatory syndrome. And so, I don't think it's too surprising that plasma exchange may increase IRIS."

http://seekingalpha.com/article/1008...age=-1&qa=true

Since there are NOW only 4300 who have been on 24+ months (since the trials), but 6300 were stated to have been on 12+ months in their Dec /07 numbers (that you had linked, Chris), either they must have included the trial participants back then, OR there has been a HUGE drop-out of longer-term users since then . . .

Perhaps we'll never know . . . but at least going forward we can calculate a semi-relevant risk (and it is NOT 4:37,600, 4:48,300, OR 1:1000, for now).

Cherie

Amazed you found the BiogenIdec so fast, as I was just getting around to post it.

So now there can be no disagreement about the postmarketing numbers of patients on Tysabri. I still firmly believe that you cannot mix the post marketing PML cases (4) with the pre marketing PML cases (3) because of the changes implemented for commercial use - wash-outs, montherapy, TOUCH program in the US.

As far as additional "possible" PML cases, remember BiogenIdec just informed us that there were no additional cases as of 1/09/08.

I was aware that they were going to announce the numbers on the 13th . . . so they were fairly easy to come by.

I suspect there will be "revelations" for quite some time about what "might" unduly influence the PML risk (like mono vs. combined therapy, the prior use of certain types of immunosuppressants, etc.). There may even be some people that are given plasma (and perhaps IRIS) simply because they "suspected" PML . . . only to determine they didn't actually have PML in the end.

I think any of these factors continue to influence the risk factor "associated with" PML or Tysabri, at least at this point.

Recently I read that they are trying to figure out which other drugs might be increasing the risk for PML . . . but they don't feel they have enough data to firm up any conclusions. In the meantime, no matter what the currently unknown 'risky contributing factors' . . . confirmed (and/or treated for PML patients) should be counted, IMHO.

What would be ideal is if they can eventually determine the "X" factors, and eliminate PML (and IRIS) completely . . . then the "prior" ratio will be irrelevant to everyone!

Maybe they've changed their since their Q3 report, but a few months back they said that they do no longer intended to report EVERY single case as they occur:

"Jason Zhang - BMO Capital Markets
I have a question again on TYSABRI. You have so far reported PML cases when they appear and I have heard some, I don't know suggestions or rumor that you may decide not to do that because you consider this as a severe adverse event, not different than many other severe adverse events with other drugs. Could you comment on that?

James C. Mullen - President and Chief Executive Officer
Yes, this is Jim. I'll take that. We've reported on PML specifically, and particularly in these last two cases, because they did represent new information and important new information . . .

This product, we're evaluating how we do those communications, but fundamentally this is an adverse event that's in the label, its in the Black Box warning. Its sort of time I think to progress to looking at the overall safety and benefits of this product and updating in its entirety as appropriate. So, we are not necessarily going to report every single case as they occur, but only if it really provides substantial new information."

http://seekingalpha.com/article/1008...age=-1&qa=true

And on their first posting to the Biogen site, they reiterated that "The first such posting today includes only previously disclosed cases of PML":

http://www.sec.gov/Archives/edgar/da...3544bie8vk.htm

HOWEVER, I am NOT worried that they are holding back on any confirmed cases at this point . . .

My concern lies with the "suspected" cases of patients that were apparently just 'taken off' the med. As per my prior message, what we don't know is if they are just NOT able to confirm (or rule out) some cases . . . so those aren't counted, or ?

Anyway, yes we have a ratio to go forward with, and I hope to see that drop more and more as "experience" is tallied over time.

Cherie