Tysabri
 

There have been 2 new cases of PML.

http://www.marketwatch.com/news/stor...3EED44821F8%7D

Wow Snoopy, this has only barely hit the wires.

Hopefully it's not true. :(

Cherie

I know it's only 2 cases in many thousands of Ty users, and yet it still is a worry. :mad:

You've been warned, so, now, it's a chance you choose to take....Be careful out there..:hug:

Thanks, Snoops.

Does anyone have confirmation on how many people are on Tysabri?

I got this 2-yr birthday announcement from the MSF earlier today, stating that close to 18,000 people were on it:

http://www.msfocus.org/online_newsDetails.php?ID=213

Other articles I read say "Tysabri was being used on more than 31,800 patients":

http://www.marketwatch.com/News/Stor...675091FAB73%7D

Cherie

Their stock lost 85% of it's value in ONE day!!! I am concerned..

So far, everything I've read says:

"Shares of Biogen fell $12.26, or 17.6 percent, to $57.49 in after-hours trading."

"Shares of Elan fell $7.60, or 37.9 percent, to $12.45."

Something to be concerned about though, which is a new consideration for users:

"The three 2005 cases (of PML) involved patients who were simultaneously taking another MS-fighting drug; such combined therapy has been banned since 2005.

The patients in the most recent case had a history of taking other MS drugs but had been on Tysabri alone for at least 14 months, according to the SEC filing."

(From what I've read, one patient was on Tysabri for 17 months, and the other for 14 months.)

http://biz.yahoo.com/ap/080731/bioge...drug.html?.v=3

Even though Biogen has been forthright about the potential for new cases of PML to occur (no one can sue ;)), there was always the thought that the first cases occurred because the people had used Avonex as a combination therapy and/or the patient (Crohn's) had been on very strong immunosuppressants previously. So far, it doesn't sound like these two people were using anything else (except maybe steroids, which have not been considered a problem with Tysabri).

Biogen Idec and Elan Corporation, plc Host Conference Call For Investment Community, Scheduled to start Fri, Aug 1, 2008, 8:30 am Eastern:

http://biz.yahoo.com/cc/9/96099.html

Cherie

Hi Cherie, your first link was a dead end. Can you cut and paste? Thanks.

I wonder if they're using the TOUCH program in Europe? I think that's where it happened. I wonder if these two could have been taking other immune suppressant drugs?

This is so sad. I hope they were able to get it out of their systems quickly enough to avoid too much damage. :(

This one?

http://hosted.ap.org/dynamic/stories...DEC_ELAN_DRUG?

or this one?

http://www.msfocus.org/online_newsDetails.php?ID=213

They all seem to work for me.

Hopefully it works for you now.

Cherie

They have a modified TOUCH protocol, as I remember. It's not as stringent as the one here in the US.

I am sure that there won't be any stones left unturned by any investigative body regarding these two cases.

Considering the fact that these are the first two MS cases of PML on monotherapy, I am sure that everyone will be on high alert.

Sally, this link has the amount of people using Tysabri. However, I am not sure if the number is correct. It seems numbers vary depending on what news report your reading.

http://www.bloomberg.com/apps/news?p...kFY&refer=home

More than 31,800 multiple sclerosis patients use Tysabri, Biogen spokeswoman Naomi Aoki said. About 14,000 patients have taken Tysabri for more than a year, and 6,500 patients have taken it for 18 months or longer.

Thanks! Now it seems to be working.

I wonder if this is what HarryZ was referring to awhile back. I would be interested in what he has to say.

Harry are you out there?

This is now on the Patient Information Warning Label for Tysabri.

http://www.tysabri.com/tysbProject/t...q.xml#casespml

Additional information:

One of the patients, the one who is hospitalized and has been on Ty for 14 months, has a history of prior disease modifying therapies including azathioprine and beta-interferons.

both patients are still alive and one has had a plasma exchange which is what the protocol is for PML.

The EU does have a modified TOUCH protocol.

Hi Cheryl. Thanks for the info. Where did you find it?

News article. I just read everything on the internet. It is actually part of the report filed with the SEC.

http://www.sec.gov/Archives/edgar/da...14958ke8vk.htm

As for the TOUCH protocol, I've been involved with the FDA and RISK Management panels. I went back through my notes from the last conference.

I went to a seminar about two years ago. Of course, Tysabri risks were brought up. The neuro said they didn't expect to hear anything for 2 years or so. It was then, he said, that they expected more deaths.

I hope this is not the start of it.

Ah come on, Vic! You? Wanna jump out of my airplane?

That's what I got out of the SEC filing information is that the protocol wasn't followed. Oops!

Well, I'm very thankful there is a protocol, and this is the reason that many of us fought for a program such as TOUCH to begin with.

What wasn't followed though, Cheryl?

From what I've read, all we know is:

- that one of the patients took Beta-interferons (which many of the people now on Tysabri did at some point)
- that the same patient took another immune suppressant drug previously (but we don't know when, and far as I know there is no guideline saying she should NEVER have taken Tysabri, if she did :confused:)
- that neither patient combined Tysabri with any other therapy
- that the second patient has never taken any other disease modifying or immune suppressant drugs

What I did see from the safety and prescribing information, a person should not take Tysabri if they have:

- PML
- Are allergic to TYSABRI or any of its ingredients

... or if they are "TAKING medications that could weaken their immune system". Other then that, a person is meant to "talk to their doctor about medications" they've taken in the past. We don't know that this patient didn't, do we?

The allergic reactions they say to look out for include such things as hives, itching, chills, rash, nausea, etc. . . . but since most infusion centers now pre-medicate with antihistimines, I don't see how they would know if someone is allergic anyway. :confused:

Because of the yet unknown risk for PML (as a monotherapy) Tysabri is also only generally recommended for those who have not been helped by or are intolerant of other therapies . . . yet we know first-hand that neurologists are recommending this med as a first line approach to treatment now.

Seems to me that no one is actually following the proper protocol now, so every PML case is likely to be a "oops".

Cherie

AZO is not to be taken with Tysabri. Even though the report says Monotherapy, that means only ONE DMD. AZO is not a DMD as defined by the FDA and the TOUCH protocol. It's Imuran, an immuno suppressant used for kidney transplants (most commonly). Not used for MS.

I am by no means an expert, Cherie, but all we can do is wait for the final report.

"we" don't know anything more than what's been published thus far and "I" am only reporting what's been filed by Biogen with the SEC and expressing my opinion based on my experience and knowledge.


Just a reminder that when Tysabri was first released, everyone was pre-medicated with benadryl and tylenol 30 minutes prior to the infusion.

This is just like the same hype that everyone went thru when Ty was pulled in 2005.

"Patient in EU with MS with a history of prior disease modifying therapies including azathioprine and beta-interferons

The patient did not take AZO with Tysabri, so far as we know. She took it prior to Tysabri.

Are you reading that the patient took them together??

Cherie

I know everyone gets all in an upset when anything negative is reported about Tysabri. However, does anyone know the fatality information for the interferon treatments? If I remember correctly - (and I don't always!) - I saw something in the last few months that listed interferons as one of the top 10 medications leading to death.

I agree with Victor - then again, I, too, have jumped from a perfectly working airplane @ 13,000 feet. ;)

I know when I pushed to get on Tysabri, it was worth every risk...because the risks were small when compared to the possible benefits. Then again, I also just opted to have my immune system killed off and re-booted. Guess I'm a risk-taker?

Hopefully we will have more information soon and that the panic doesn't get out of control.

~Keri

Do you know that for fact? I don't and I am done with this.

:)

It doesn't say when she took it. It just says history which could mean yesterday. You know that as well as I do. They aren't going to release any more information than they have to.

My point is that they are saying it's a DMD and it's not. It doesn't say WHEN she took it. She has a history of it, period.

I don't know any more than you do, unless you know this person or are her treating physician. I don't and am not.

If you will remember, that was one of the drugs that the Crohn's patient had on his list of drugs that he had taken some time during the clinical trial but not concurrently with Tysabri. He contracted PML and subsequently died.

It's not necessary to red bold for me, I can read. ;)

Good night Cherie. :D

You were the one that suggested there was an "oops" in protocol, but I couldn't see where there was one. :confused:

I took the "facts" from the Tysabri prescribing information that you posted:

And the patient details from "UNITED STATES SECURITIES AND EXCHANGE COMMISSION report (that you also posted):


Your link says "prior" use of AZO, which was obviously "prior" to using Tysabri (since that same link also says the patient was on Tysabri monotherapy):

"Case 2
• Background:
- Patient in EU with MS with a history of prior disease modifying therapies including azathioprine and beta-interferons;
- TYSABRI monotherapy for approximately 14 months;

I don't see what relevance (what they are calling it) has to anything :confused: . . . but if you "Google" Azathioprine, it is included as a "disease modifying therapy" by many sources, as per this (UK?) government site:

http://gateway.nlm.nih.gov/MeetingAb...102271717.html

As to your second point, it does say "prior" to Tysabri monotherapy. Seems pretty clear to me. :cool: Yes, we don't know when . . . but we also don't know if there was an "oops" then either, do we?

None of this changes people's choice to take risks, of course. All it does is more clearly define what the actual risk may be to monotherapy Tysabri . . . and then it's up to the patient to decide if they want to go for it anyway.

Cherie

I agree that this new information is NOT worth panicking about.

It's just another piece of the puzzle for people to consider.

Cherie

All I know is that the company expected more cases of PML and made us aware that liver damage could occur in as little as 6 days, in a statement a few months ago.

http://www.fiercepharma.com/story/bi...pml/2008-03-19

I don't know what the basis for their statement about PML was, but I think as more people are participating with this therapy, more will be learned.

Everyone has a different way to assess the risks they are willing to undergo, and we are all learning from one another, in the end.

Just wanted to make a couple of points:

• Not all infusions centers in U.S. are following the required touch protocol.
• I was told at the MS center at Barnes Hospital that immuran is being widely used for ms in Europe. It was suggested as a therapy I might consider.
• Predosing with benadryl does not always mask allergic reactions to tysabri. (I know from personal experience.) I am not sure how a discussion of predosing and allergic reactions is related to PML's.

WHUH?? I guess I don't know what the big hoopla is, here. Everyone going on TY now, is made aware of the risk of PML and liver problems and infection...etc... It's on the black box.

You all voiced worry about it, when you first started it, but you are making an informed decision, when you do. Now that the prediction has, possibly, come true, is unsettling to say the least, but, not surprising.

In my mind the time to panic has passed. I paniced when TY was first pulled because of the PML deaths, and believed it should have stayed off the market.
You all wanted it back and you got what you wanted.

On the other hand, there are a bunch of lethal drugs out there, that we seem to demand......we pays our money and we takes our chances. We're all in a Trial for these drugs, we're just not gettin paid for it.:rolleyes:

I agree with you, Sally.

Everyone who has decided to use TY has done so with full knowledge.

But, it's still sad to hear that PML is once again linked to Tysabri regardless if TOUCH was followed or not.

I was trying to figure out why Cheryl thought there was an "oops" in the protocol for this patient, so I reviewed the "Patient Information Warning Label" for Tysabri that she had posted (in posting #16):

I could not find anything in the warnings that implied an "oops" may have occurred when treating this patient with Tysabri. What I did find, however, was the following warnings:

http://i12.photobucket.com/albums/a2...44/Tysabri.jpg

Why an allergy to the drug is considered a NO-GO for Tysabri, I don't know. However, they seem to think it's important enough to put it on the label (including describing what an allergic reaction might look like; hives, chills, etc.) as contradictory to using the med.

My point was, how can they know if someone is allergic, ie. if Tysabri SHOULD be a NO-GO for that person, if they are premedicating most people with antihistimines?

On that basis, couldn't every PML case be considered an "oops", since patients shouldn't even be taking Tysabri if they are allergic (according to the labeling)?

Cherie

I think it's important to keep the reality of proportion in mind when we look at this stuff. PML incidence is on the rise globally, so it stands to reason that it is on the rise for those with MS. Lower incidence rates in underdeveloped countries are attributed to their lack of diagnostic opportunities.

Those with compromised immune systems are at a higher risk for PML across the board and this has been the case since way before Tysabri and its use ever hit the scene.

This is a small section of the basic list of PML attributes from the Neurological Medicine Pocketbook for physicians published by the University of Western Ontario, Canada:

- Multifocal demyelinating lesions of CNS
- Due to reactivation of JC virus (papovavirus)
- 90% of general population have serological evidence of JC virus infection which is benign / asymptomatic
- PML occurs in association with immunosuppression (esp HIV / AIDS), leukemia, lymphoma
- The incidence of PML dramatically rose in the 1980’s with AIDs
- Up to 4% of patients with AIDs develop PML at some point during disease
- The incidence of PML has NOT changed with introduction of HAART (highly active antiretroviral therapy)
- JC virus infects oligodendrocytes, leading to lysis and demyelination


Full List:
http://www.uwo.ca/cns/resident/pocke...ection/pml.htm

As far as track records go, Tysabri is still safer at this point than Cellcept. There are 17 confirmed cases of PML with Cellcept and 6 of the cases were with people who had lupus. Why isn't there a huge public fuss in the media about Cellcept? I'm sure the same old arguments about safety v. danger with Tysabri will be hashed out in the coming days. In addition, Cellcept is being prescribed off label for MS and UT Southwestern Medical School has been doing clinical trials on Cellcept in combination with Avonex. Now we don't know what the extenuating circumstances are (maybe Cellcept was being mixed with other immunosuppresants) but the point is there appears to be a risk with some of the newer drugs coming out. And as AftermyNap says, maybe PML is also on the rise?

We got into that discussion a while back, in the following thread:

http://neurotalk.psychcentral.com/sh...hlight=Tysabri

In the case of those with HIV, they don't seem to know why those patients are ending up with PML, so the largest percentage of PML cases on record (currently) are probably inevitable. Unfortunately, AIDs often leads to an untimely death even without PML as a complication. :(

With other diseases like cancer or organ transplant, it seems like that it is the use of these strong immunosuppressants that might be causing PML. I'm not sure they have any choice in using these drugs in many cases though; it's either die (rather quickly) from the condition, or die from complications due to the meds. :confused:

With MS, and Crohn's, there are other options available, that do not include this particular risk for PML. And, from the information I posted in the above link, those options are thought to be equally effective in treating this disease.

I don't think anyone is saying that it is advisable at this point to remove this drug option . . . but I think it is important to appreciate that it seems PML can occur from Tysabri as a monotherapy. This discovery is not going to change some people's minds to try it anyway . . . but it WILL likely change others.

Cherie

Yes, I was the one who mentioned the studies going on with Cellcept and Avonex at UT Southwestern. I was asked if I wanted to participate and I declined.

You have to remember that some people have run out of options because the meds don't work or they cannot tolerate the side effects (quality of life issue). :(

Statistically, this is incorrect. CellCept, and Rituxan, have both been used on hundreds of thousands of patients, so the percentage of patients using those drugs that get PML is quite small. The problem Tysabri faces is that it might show a higher rate of PML infection among the patients taking it. There are an additional 12 cases of suspected PML in Tysabri users currently under investigation. If these turn out to actually be PML cases, then Biogen will have a very big problem...

http://tinyurl.com/5turuy

Thanks Marcstk. That makes perfect sense. You have to consider the number of cases v. number of people on the drug (and then really over a certain time period).

I tried to find more information on the 12 suspected cases in the FDA Adverse Event Reporting System (as mentioned in the article you list) but couldn't find anything. I may not be using the right search terms.