Can someone please explain why Biogen is now stating that the risk of PML is still 1:1000 from 24 to 36 months if only 13,000 people have taken the drug more than 24 months? I got the 13,000 number from an article dated Oct. 23. Haven't 18 of the PML cases been 24 months and over? Thanks!!!!

You can use statistics to prove/disprove almost anything you want. It all depends on what data you use to obtain your numbers.

People think that if 1000 people take Tysabri and 1 gets PML, then that means the risk is 1:1000. When it comes to statistics, this may not be true at all because one has to work with probability and several factors have to be taken into account to obtain the real risk factor.

Now it may very well be the risk is 1:1000 but the chances are slim that it is because of the many factors that would have to be considered here. But I would guess that Biogen is going to use the number that makes Tysabri as attractive a MS drug as possible.

Harry

Natalie,

Part of the problem lies in the fact that the PML case number is as of a relatively current date (Late Oct) and the 13,000 patient number is as of Sep 30th. More patients crossed the 24 month threshold in that time.

The other part of the problem is how ratios are calculated statistically with this small sample size. Because of this small sample size, there is potentially a large amount of variability in what the real answer will ultimately be. These calculation methods are universally accepted, hence the FDA's concurrence that the PML risk is similar to that seen during clinical trials.

Update today from Biogen of the JCV Assay
 

http://www.wsw.com/webcast/lz6/biib/index.html

Of course to the financial community. Biogen was asked in the Q&A portion about the timeline for the assay - reply was months to quarters, big hurdle was to work with the KOLs (key opinion leaders) on how to utilize them (presumeably more of an issue for the 50% who would test positive as having the JV Virus dormant in their systems).

Chris

http://www.independent.ie/business/w...t-1946602.html

MS wonder drug 'balanced alert'


Wednesday November 18 2009
PHARMACEUTICALS
Elan and partner Biogen Idec aim to find a "balanced way" of alerting investors about the number of brain infections linked to their Tysabri multiple sclerosis drug by the end of this year after a surge in cases, CEO Kelly Martin said yesterday. It was recently confirmed that Tysabri has been linked to four deaths and 24 cases of the deadly brain infection known as PML since the product was reintroduced in 2006.




Anyone see anything missing in this statement?

WTF!!! What about the PATIENTS???:mad:

Letters streaming forth to both...GRRRRR.

Before you get too exercised about this, remember he is talking to a financial news source and the financial news source's only concern through this whole PML process has been the number of cases and the reaction it causes to the stock price. Who knows all of what was said and clearly the financial news source may have selected what they felt was important.

I understand that it was a financial news report. Regardless of who the statement was directed at, the patient should never be left out of any statement when it comes to side effects and problems with a drug. They should always come first. Elan and Biogen would do well to remember that, and to emphasize it in every statement they make, and I for one will remind them at every opportunity.

I do not ever forget that if it wasn't for us, they wouldn't have a drug on the market, nor would they be making what amounts to over a billion dollars a year at this point in sales of this drug. I do not ever forget that while they may have to spoonfeed investors, the very people who are taking the drug are the most at risk and what those patients are risking means a whole hell of a lot more than money, and both Elan and Biogen should remember that too, as should every other drug company out there that markets a drug and makes money from it.

Go RW!!!!!! You are so right about the patients. I love how the article states they are hoping to find a "balanced way" of letting investors know about the PML risks. Ha ha ha. That is shorthand for "leaking as little information as possible."

In the meantime, there have been 3 more PML cases added to the German blog for November. :( All it states is that the info came from an "internal Biogen paper." If this is true that would now make 27 post-marketing cases.

http://chefarztfrau.de/?page_id=716

RW, do you know anything about this?

Three more cases of PML in Germany? Did anyone else get this information? :(

http://www.xconomy.com/boston/2009/1...ngle_page=true

Tysabri, the MS Drug Haunted by Deadly Side Effect, Doesn’t Look So Deadly Anymore


Good discussion of efforts in work on the JC Virus/PML front

Up to date info on PML cases/deaths/patients exposed

This is the testing was talking about, that should be done before a newby goes on Tysabri....Quoted from the above link...

Thanks K.

http://blogs.wsj.com/health/2009/11/11/when-rival-drug-makers-compare-notes-on-safety-problems/tab/comments/

There are several Wall Street Journal articles about Tysabri and Biogen if you go there and search. You can also leave comments. :)

Progressive Multifocal Leukoencephalopathy and Relapsing-Remitting Multiple Sclerosis
 

http://www.projectsinknowledge.com/c...3.05&pretest=y

A comparative study, interesting and informative when it comes to lesions and the differentiation between the two diseases.

(PS: I haven't had a chance to do any investigating on anything that has been posted about the reported new PML cases. I had too much RL to deal with today and I am going to BED! :p I'll try to find more this weekend if I have time!)

"inhibitors such as caffeine are potential therapeutic agents for JCV infection."
 

http://www.ncbi.nlm.nih.gov/pubmed/19903823


J Biol Chem. 2009 Nov 10. [Epub ahead of print]

Large T antigen promotes JC virus replication in G2-arrested cells by inducing ATM- and ATR-mediated G2 checkpoint signaling.
Orba Y, Suzuki T, Makino Y, Kubota K, Tanaka S, Kimura T, Sawa H.

Hokkaido University, Japan;

Large T antigen (TAg) of the human polyomavirus JC virus (JCV) possesses DNA binding and helicase activities, which, together with various cellular proteins, are required for replication of the viral genome. We now show that JCV-infected cells expressing TAg accumulate in G2 phase of the cell cycle as a result of the activation of ATM- and ATR-mediated G2 checkpoint pathways. Transient transfection of cells with a TAg expression vector also induced G2 checkpoint signaling and G2 arrest. Analysis of TAg mutants with different subnuclear localizations suggested that the association of TAg with cellular DNA contributes to the induction of G2 arrest. Abrogation of G2 arrest by inhibition of ATM and ATR, Chk1, and Wee1 suppressed JCV genome replication. In addition, abrogation of G2-M transition by Cdc2 depletion disabled Wee1 depletion-induced suppression of JCV genome replication, suggesting that JCV replication is facilitated by G2 arrest resulting from G2 checkpoint signaling. Moreover, inhibition of ATM and ATR by caffeine suppressed JCV production. The observation that oligodendrocytes productively infected with JCV in vivo also undergo G2 arrest suggests that G2 checkpoint inhibitors such as caffeine are potential therapeutic agents for JCV infection.

"inhibitors such as caffeine are potential therapeutic agents for JCV infection."

Who knew that all those gallons of coffee that this night worker drinks woud be considered neuroprotective! Here they've been telling me all these years that I need to cut back! :p

I am currently getting #18 right now! It was nice to have the IV go in easily the first time. I had to delay a week because of a persistent UTI and I was in Mexico. Somehow this time around the delay didn't worry me like it did the time I was delayed a year ago due to a respiratory infection. I wonder what made the docs decide that every 4 weeks is better than say every 5 or 6 weeks? The weird thing is I can't tell a difference in how I feel. If anything I seemed to have a little more extra energy at the end and before the next infusion. I'm starting to figure out that the Tysabri wipes me out for a good 7-10 days. I feel so drowsy all the time during those days and my brain is a little foggy or slower.

Natalie,
Your post makes me wish yet again that my infusion center had wireless internet available! I'd be yapping away the whole time.

Glad to hear that the IV went in smoothly, I've been having the lidocaine pop before the IV for the last few infusions, they didn't ever offer it to me before and I find it really helps to stop the aching from the IV during infusion.

People who are in touch with their bodies amaze me. The only thing I remember about any adverse effects during infusions are the sore throat I had after the first few infusions and that stupid pinpoint itch. I don't remember being any more or less fatigued than usual, or achy, cranky,etc.

I hope the Mexico trip was for fun!

Hi RW -- Mexico was great! It was nice to check out of reality and be away from phones, email, internet, students, and MS! What's the lidocaine pop?? You know, I got a couple of sore throats the first 2 infusions also. Weird, huh? For some reason today I'm feeling pretty good--not many side effects from the Ty. It's so hit or miss sometimes and I have no idea why.

The lidocaine pop is when they inject a bleb of lidocaine under the skin where they do the IV. It stops the sting from the needle going in, it doesn't hurt when they go fishing and it stops that ache at the site when the IV is running. I tried it a few months ago and I swear by it now, since I always had that ache, sort of like you left ice on a sprain for too long.

The sore throat thing was after my first two or three infusions. It was like mild tonsillitis. I grew back part of my tonsils after removal when I was 4 or 5. I always had mild sore throats through the years when they would get inflamed during a cold or whatever. I got one after the first few infusions and I haven't had one since! Maybe Tysabri blocked the T cells there too!

No more Tysabri! I'm starting Copaxone soon then wait for Cladribine.
 

I just spoke to my MS neuro and I'll be starting Copaxone again as soon as the insurance approval comes through and they send it out to me.

I did ok on it and I can take it until Cladribine is approved.

It wouldn't make sense to start Tysabri again for a short time then have to take a drug holiday before starting Cladribine.

I call tomorrow to get the shipments of Copaxone set up and ok'd with my insurance.

So, no more Tysabri for me and I think this is a good plan. :)

BTW, he thinks Cladribine will still be approved in 2010 but maybe not as soon as he had hoped.

Wishing you my best Wiz :hug:
Linda

Wiz,

I'm happy you have a plan for treatment that you are happy with. :highfive:


More than anything else associated with this crap, we have to be comfortable with what's involved with the treatment or we don't stick with it, and you are on track already with your plan.


I've appreciated and enjoyed the support you have given me all the way through our journey together. You'll always be my Ty twin! :hug:

:eek: Glad to see you made it home ok!

The chair can lull me to sleep every time and ours are not even that comfortable!

Yay for #9! :)

Wiz, I know this is off topic but I just had to say Daisy the kitten looks absolutely precious.
I am an animal lover :D
Linda

Hi Wiz, good luck with the copaxone. Sounds like you have a plan.
Polar, congrats on #9. Sometimes I find the Tysabri makes me very very sleepy, even for several days afterward.

You too RW! :hug:

Thanks Linda, She is precious but such a livewire! :D Our three year old tabby Rocky is having an adjustment period. :eek:


Thanks Nat! :hug:

Polar,

There's no way I could drive myself home after my infusion. DH has had to usher me for all 31 trips, lol. I'm sure he's secretly happy he won't be making that monthly trip anymore, :cool: especially in the winter when the roads can be treacherous.

had my 1st ever tysabri infusion yesterday
 

Well, it went great thanks to the person in chair next to me getting chemo from my home town. Side effects? well, today I feel like I have slight Rebif aches. I also was up later then usual last night since it was last night parents were here before flight home. Sleep + Advil should do it..hopefully.

ewiz - Copaxone worked wonders on me from 06 - early 09 then began nose dive. Rebif mid year didnt stop the decline. Returned to Copaxone 2 months back with numbness progressing on daily/weekly basis. Hoping Tysabri will do it without doing me in. We'll see. Yes I exercise. Testosterone helped big.

Edife, hope you do at least as well on Tysabri as I have-I just had #40:D
Best wishes and good luck!
Linda

Wiz: I'm the only one here who drives, so not a lot of options. Your DH may not say it, but I'll bet he's not complaining about not driving to infusions either :D. I hope the change in meds works out great for you, and Grammie's right ~ Daisy's almost TOO adorable!:D

Edife: Glad the 1st infusion went well! I hope this does the trick for you.:hug:

Thanks. 3 days later I still have Rebif foggy head/slight pain.
Question I have is does Tysabri make poop smell worse? I think mine does.
Sorry if that's not a "eye friendly" question but i'm wondering.
I also get chilled more then usual. Haven't called to ask if that's why I was sent a blanket.
Can't say feeling/strength is improving or worsening yet. Let's hope.

Congrats on your first infusion Edife.

Glad to hear Biogen is sending stuff to everyone. I must be on their list of naughty peeps cause I don't get presents from them. They must be sick of seeing my name in their inbox all the time! :p

# 33 down!

No problems, no concerns, as usual.

Infusion was followed by a LONG appointment with my neuro, his increasing concerns and request that I entertain thoughts of a drug holiday, my reassurances that the holidays we already have in the next few months are enough for me, discussion about the drugs in the pipeline, CCSVI and medical marijuana laws.

We agreed that I will have my next three infusions, he is going to a peer conference in January and we will met again in February and discuss any new information.

I left with an order for blood work, MRI, and a medical marijuana letter.

:D

RW--congrats on #33. I'll be interested to hear what your neuro says in 3 months. Did his concern and call for a drug holiday scare you? Send me a PM--I would be curious to know what he said about CCSVI. :hug:

Edife, everyone hopes to see sx reversed by Tysabri and if that does occur it usually around 4-6 infusions and then might be so insignificant you almost miss it. Tysabri claims to slow/halt progression by 66%, for better MRIs and less exascerbations (will somebody PLEASE tell me how to spell that word :))

Linda

Polar, I just had my 28th infusion and it always makes me very sleepy. I usually fall asleep during the infusion, sleep all the way home...my husband drives me to and from infusions because of the sleepiness.....and then I sleep on and off for several days. I thought I was the only one who was effected by Ty this way...LOL Congrats on #9. I hope it works as well for you as it has for me.

I had my 28th infusion with the normal side effects for me......headache, achy feeling all over, nausea, abdominal pain and the chills. I'm always cold :(

My neuro and I spoke in October about having infusions every 8 weeks instead of every 4 weeks. She doesn't think it's a good idea to wait that long. But, she is hoping that there will be another alternative to Ty soon. I attended a seminar recently and the 2 neuros there spent a lot of time discussing Ty. They are both having their patients who have been on Ty for 2 years go every 6 weeks instead of every 4 weeks. My next infusion will be in 5 weeks due to the fact that my infusion center will be closed for the New Year and a few days afterward. I'm going to see how it goes. In the past when I've waited 5 weeks between infusions I didn't have a problem...no wishing I could have my Ty "fix" already. So, if I don't have a problem waiting 5 weeks between infusions I'm going to try 6 weeks between infusions. BTW, Biogen sponsored the seminar.

At the infusion center I go to they do take my vital signs before the infusion but they only will do blood work every 4 or 5 infusions and although they ask the necessary questions before the infusion I rarely see the oncologist who is there. He does check my chart every time I'm there because I have heard him ask the infusion nurse for it. But, apparently since I'm doing ok he doesn't feel he needs to see me very often. That is going to change. My insurance has told him he must see me every 3 months or they won't pay him....LOL

I'm praying for some type of test to see who is vulnerable to PML and who is relatively safe. Ty has been so good for me that I want quality of life more than quantity of life. I'll never have my "old" life back...the life I had prior to the severe exacerbations. But, I'm able to exercise, walk 1 1/2 miles without difficulty, drive a car again and see friends when I want to. That's better than being in a wheelchair and completely dependent on my husband!!!!!!!!!!!!!

My only concerns other than PML are that I'm always cold now, if I hadn't been a vegetarian prior to the infusions I would be one now....I can't stand the smell of meat, poultry or seafood!!!!!!!!!!........and between the infusions and trying to get back to California on a regular basis to see my grandchildren I feel like I am always recovering from something.....the infusions or the visits to California which leave me exhausted :( I can't move back there because I can't sell my house or even rent it with the economy the way it is. And, I live in a retirement community which means less people are qualified to live here. If only I knew what MS would do to my life when we retired here 8 years ago....LOL I had always taken it for granted because I always went into a full remission. And the severe exacerbations had been few and far between. But, the exacerbation in 2003 was the one that broke the camel's back. I'll never take anything for granted again.

Life is better with Ty. So, until there is something else out there for me I'll take my chances and stay on Ty. But, I'm going to try and cut back on the number of infusions every year. If waiting 6 weeks between infusions works for me after several infusions I will attempt to wait 7 weeks between infusions.

Rumour has it that the JC Virus Antibody Assay will be available in Q1 2010 (Maybe even January). This assay will allow the identification of patients who have not been exposed to the JC Virus (No antibodies) which should mean a very low risk of PML. Per the companies, approximately 50% patient are JC Virus Antibody negative. Big effort right now is working with Key Opinion Leaders on treatment guidelines for patients who test positive for JC Virus Antibodies.