It sounds like the JC antibodies test has not been made commercial yet. In other words, it is still in a "research phase" and not available to the public. Hopefully Elan will put a rush on this if it actually works consistently.

It's because they didn't have those samples in front of them at the start and the samples had to be tested, Sal. At the time it was also believed that 90% of the world population carried the JC virus. The rate is now believed to be around 50% of the world population. It was also not easy to test for it and it was extremely time consuming and expensive. I don't believe that in a controlled trial environment, the patients names would have been attached to the samples either, just a control number.

One thing that IS happening with all this is that the science of understanding JCV and PML is being advanced and this will benefit a huge number of people, not just those with MS who are on Tysabri. It will have implications across the board, since it's been a problem with other drugs and other diseases.

IMO, Ted Yednock is a hero! His work in the field of MS treatment and now in working on this issue puts him at the very top of my list of people who deserve a Nobel prize in medicine!

Here is an article suggesting that the monitoring of Tysabri in Europe (and in particular Germany) is lax and this might be one risk factor for higher numbers of PML. Interesting.....

http://industry.bnet.com/pharma/1000...opean-doctors/

Here is the announcement of the 24th case which Riverwild mentioned to us in a previous post. Your sources are good RW!

http://www.mednous.com/news/emea-rec...linked-tysabri

Wiz, I don't get it. How can the Senior Director of Patient Services keep claiming that the risk is 1:1000 and won't acknowledge the risk is greater with more infusions? I ask this because according to this article in International Business Times Biogen people told investors on a conference call on Oct. 20, 2009 that the risk increases with a greater number of infusions. :confused:

http://www.ibtimes.com/articles/2009...data-mixed.htm

This makes me angry because it seems like they are telling investors one thing but patients another thing??

He did say the risk is more with an increase in infusions, but that even those people fall within the 1:1000. Those patients with less infusions have less risk. Sorry I didn't make that clear.

He also said that they do not recommend taking a break from Tysabri. When I asked him about the comment someone from the help center said to me yesterday, that disease activity seems to resume after about six months from stopping Tysabri, he admitted he didn't know that for sure, but that if somebody told me that from his support center, it's definitely true.

Thanks to everyone who is advocating on behalf of all Tysabri patients.

The earlier link posted by komokazi http://www.forbes.com/2009/10/27/ms-...rtner=yahootix gives enlightening information not only about the JC Virus testing being developed, but the number of PML cases and the new "odds" (1:400). :eek:

I'm getting more concerned with each passing day that we do not have 100% of the information we need to make good decisions.

I am postponing my 37th infusion in 2 weeks until after my scheduled MRI on 11/12 and a thorough and frank discussion with my neuro.

Be well,

Still don't get where anyone can come up with 1:400 odds as I posted on the other site.
I, also, still believe that 4 maybe 5 (depending where the 24th case is) cases of pml are in the U.S. which makes the odds here much better than even 1:1000 since there are, as of a couple months ago, 22,000 on Ty in the U.S.

As I was typing my Touch case manager called me. He took notes, understood all my concerns and will pass it on. He said we are being heard and the higher ups are discussing what will be done to give us information. He confirmed what I typed in the previous paragraph about how many U.S. cases and how many are on Ty.

I still think we must be vigilant and informed !!
Linda

Howdy folks!

I just woke up and I am happy to be done with work for the week! I have Saturay night off too! My DSD is having her Senior Recital that night and it is also her birthday, and I am looking forward to both!

I had a FULL box of emails today, and a full box on the answering machine, with several calls from people at Biogen. I'll let you all know what they have to say when I call them back tomorrow.

WE ARE having an effect. One of the calls was from someone high up in the company whom I haven't heard from since 2006, after the FDA hearing.

Here's what I have for new information. This information is from a trusted source who was inolved in bringing Tysabri back to market.

"The EMEA says that four (4) of the confirmed 24 PML cases have died. My contact has been quite clear that the early three cases (pre-2006) are not included in the 24 cases, but I hold out hope that the two early deaths account for half of the four reported deaths (US patient whose family declined to follow the recommended PML treatment protocol, and the recent death of the German patient reported by his wife on the German patient website). I am seeking confirmation that the four deaths are indeed all post-2006, and will update as soon as I know more. We do know that a few of the PML patients were in serious condition, so additional deaths cannot be ruled out.
-- EMEA contact does not have information concerning the relative severity of the PML patients who have survived to date. We know that some are in stable and reasonably good condition, along the lines of a severe MS relapse, but others are more serious.

-- EMEA contact reports that all 24 patients had received between 12 and 74 infusions, that 18 of the 24 cases were reported in patients who had received at least 24 infusions, and that although the data are limited, there appears to be a trend for more cases of PML to be reported with longer duration of treatment.

-- EMEA contact reports that one of the concerns of the Committee for Medicinal Products for Human Use has been to increase awareness by healthcare professionals on how to differentiate PML from a relapse of MS and the management of PML cases, and that improved awareness is of course a factor in identifying potential PML cases that can be better evaluated. This suggests to me that EMEA action will likely be limited to updated labeling, improved educational efforts among neurologist and other healthcare professionals, and possibly a TOUCH-like program that could limit the use of Tysabri in inappropriate patients.

-- I am told that as of Friday, October 23, BIIB was aware of only one recent death (I assume the recent German male patient). That means either there were two more recent deaths, that EMEA is counting the two pre-2006 deaths in its total of four, or that someone has their facts wrong.

-- I am told that BIIB believes that they need to develop a profile on a subset of patients that is more subject to PML and that the larger number of PML cases, although unfortunate, can help this effort. No surprise there.

-- BIIB is doing conference calls and visits with the largest Tysabri prescribers this week and next week to disseminate as much information as possible. There may be more information that leaks out over the next couple of days, or we may already know much of what BIIB and the EMEA are disseminating.

I have not yet gotten any breakdown, but I am sure that BIIB will be asked about that in the two conference calls with neurologists that are taking place this evening (5:00 pm and 8:00 pm ET). "

It sounds like there is still some confusion in the numbers, but the majority of patients is coming from the EU.

The EU, especially Germany, is having problems with their doctors prescribing Tysabri to patients who were on methotrexate, azathioprine, etc and not giving enough time for clearance of previous treatments. Hopefully they will get a program similar to TOUCH in place over there or improve their monitoring of patients for early PML symptoms, and learn the subtle differences between PML infection and MS relapses! Most prescribing docs here in the USA are now saying that any activity that even resembles a relapse means an automatic halt to Tysabri, MRI, urine, blood and CSF testing, monitoring, and further treatment, including PLEX and mefloquine if there is even a hint that it might be PML.

The assay developed by Ted Yednock has been sent to a commercial company for testing which will lead to production. As with everything medical, it will have to be approved by the FDA, but I think maybe there might be a fast track on this and we will hear a lot more about it sooner rather than later.

For Linda: The number of 1:400 came from Biogen. I don't have the link in front of me, but perhaps someone here still has it at hand. I will search my files and send it when I find it. My files are all jumbled from the last few weeks as you can imagine and I have to sort and prioritize them! :rolleyes:

Wow RW. Thanks for the very useful information. I feel most optimistic about the quick production of Yednock's assay. Let's hope it will happen soon. The 1:400 risk came from Biogen? I'm quite surprised. Again, was this rate for people after 3 years?

I had infusion #17 today. The usual infusion nurse was out today (had a substitute) so I couldn't get any information. I'm still waiting for my doctor to call me back after leaving a message on Monday. That does not make me happy. :mad: It is a big clinic but really they should be care.

Anyhow, the infusion went better than usual. I came home, fell asleep for 4 1/2 hours, woke up and had just mild nausea. That's it!! This really would be the most perfect drug in the world without the PML risk. I love my Tysabri and what it has done for me (no relapses, no MS symptoms, no change on MRIs). However, my concerns about PML continue to mount and I'm not sure what I will wind up doing in the next couple of months. I'm just hoping I can get as much information as possible to make the best decision for myself.

Hi Natalie and congrats on # 17!

It's hard to believe it's been that long for you! It's hard to believe it's coming on #32 for me, sometimes I feel like I just started and that I am like a child in the dark trying to find the door especially when it comes to what is happening with us and Biogen right now. :(

I may be wrong in saying it was Biogen, but I think it was during a discussion on a possible labeling change and that the FDA may want to include updated information on risk to people who have had long term exposure and what that risk was when it was compared to the actual number of patients with long term exposure and the number of PML cases.

One of the problems that seems to be coming through is that the EU is skewing the rates. I may be way off base here, but since most of the cases so far are from the EU, and Germany in particular, there may be something going on there that we are not seeing here. It's too early to say what it is, because it may be environmental, may be due to something they do regularly and assume is ok that we do not do, may be due to previous treatments, may be that they have more incidence of JC exposure than we do, who knows...but something is going on over there. Hopefully we will get the information we need so we can continue to feel comfortable with our own assessment of our risks as patients and our choice to take this drug. :hug:

I know, I can't believe I am up to #17. It seems like I just started, for sure, and I remember the decision to start was quite anxiety-provoking. I still wouldn't do it differently though. It's funny because when I started you were on #15 or #16 and that seemed like a long time to me--now I am where you were!! :D

If I could safely stay on this drug for the rest of my life I feel like I would never have to worry about MS. As of now, I don't always think about it.

I meant to ask you -- were the last 11 cases announced since Friday all in Europe?? None of them were in the US then?

Natalie,

Honest answer is we don't know what the truth is because they won't tell us.

We can search for info and let people know what we find out, but until they open the box and tell us the truth, we cannot confirm anything. That's why I don't say anything's confirmed. I quote sources and boards and spouses and patients and articles.

It sure will be nice when I can say...This is the official statement from 'blank' :(

I'll see my neuro tomorrow for my 32nd infusion. I'll talk to him about taking a break and the new PML cases.

Since he already mentioned taking a break last month as a possibility, I know he'll be ok with it.

He was also talking to us about a couple of the oral meds that will be out soon. Maybe if I do take a break, a good one would be available by the time I need to go back on therapy.

Or, I could take Copaxone again since it worked ok for me.

RW, correct me if I'm wrong. Doesn't Biogen/Elan have to report all PML cases to the SEC? Or do they get to decide what to report? Also, they are required to report to the FDA, correct? But that FDA info isn't necessarily public, right? I think Wiz said the FDA person she spoke to told her to use the Freedom of Information Act. How obnoxious.

My neuro talked me off the edge!
 

I just got off the phone with my neuro.

I had postponed my next Ty (#37 scheduled for 11/12) until I had some answers.

The good news is that I continue to test negative for the JC Virus (A few of our local labs can test for this). My MRI's look great. I feel good.

She did tell me that the presence of the JC Virus can make one more susceptible to PML BUT the absence of the JC Virus doesn't necessarily mean one is not going to get PML. Interesting.

I also mentioned my concern about the pre-infusion question regarding 'new or worsening symptoms'. I always hated that question, because the symptoms mentioned are just normal ms stuff, and my symptoms always seem a little worse as I near my next infusion. Her answer was that symptoms that worsen just AFTER an infusion, not just BEFORE, would be a red flag.

So, in a leap of faith, I am back on schedule for Nov 12th. I'm also having my MRI that day.

My neuro wanted me to thank EVERYONE who is advocating for the information that we need and deserve. She wishes every patient of hers was as diligent...

Keep fighting & Be well,

Nope. They don't have to report to the SEC. It's not considered to be a material event that affects financial operations until the FDA says that the risk rate is outside of the label statement.

They have to report CONFIRMED cases of PML to the FDA from the USA. They MAY report confirmed cases from other countries to the FDA. Anyone can file an AERS report to the AERS database, even people like us, but it may or may not get investigated. The FDA usually does an update on their Medwatch page when something happens in the USA, not in the rest of the world, and since the USA rate is still within the 1:1000 label, I don't see anything coming soon, but I monitor the page anyway.

Natalie, it was me Barbara at the FDA told to write or fax for info under the Freedom of Info Act :mad:
Glad #17 went well for you! I will get #40 day before Thanksgiving.
Linda

More interesting info!

France has had NO cases of PML. Their medical prerequisites require them to test for CD4/CD8 counts to check the status of each patient's immune function and they do it to every patient. If the count is too low, no Tysabri until the count is normal. So, if a patient has a lowered immune system due to using another drug or anything else, no Tysabri.

JCV carriers:

"JC Virus has been used as a genetic marker to infer early human migration patterns. But new analyses show that it may be an unreliable indicator: this ubiquitous virus evolves much faster than previously thought and its evolutionary trees do not reflect known patterns of human population divergence.
Most of us contract JC virus (JCV) during childhood, from our parents. Only rarely does infection cause disease; mostly, it remains unnoticed, and we pass the virus on to our children in turn. JCV has at least 14 genetically distinct subtypes, some of which are associated with specific human populations — for example, type 7A predominates in Southeast Asians, types 3 and 6 in Africans, and types 1 and 4 in Europeans.
The parent-child transmisison route, together with the population specificity of particular subtypes, has led some researchers to use JCV as a genetic marker for tracing early human migration patterns. Furthermore, rates of JCV evolution have been inferred by assuming co-divergence with human populations over the last 200,000 years.
However, Laura Shackelton, Eddie Holmes and collaborators report that JCV and human evolution are not tightly coupled after all. When the researchers examined JCV from a variety of human populations worldwide, as well as mitochondrial genomes from the same set of human populations, they discovered that:
JCV is evolving much faster than previously thought
Much of JCV's genetic variability stems from a population expansion starting around 350 years ago, much later than early human migrations;
Evolutionary "trees" for JCV do not map at all closely onto the evolutionary history of humans inferred from mitochondrial sequences"

From a study published in the Journal of Virology

This makes me wonder if only certain subtypes of JCV are prone to developing into PML.

So many questions, so little known...sigh

Wow, France has no cases of PML? Do they only test the CD4/CD8 counts before treatment starts? Or do they also test periodically along the way, like every few months or so. Perhaps we should ask our neurologists to test for this? RW, where did you get the info on France?

So I just got off the phone with my neurologist and got some useful information. She listened to the conference call last night that Biogen did with the neurologists. Here is what I found out.

8 out of the 24 cases have been in the U.S.
60% of the patients taking Tysabri are from the U.S.
4 deaths from PML out of the 24.
64,000 are currently on Tysabri (she said this is what Biogen told them but everything I've seen in other articles says roughly 46,000--so this was confusing even though I asked her if she was sure). Take this number with a grain of salt. Maybe she flipped the digits in her mind.

It's not clear how long the EMEA had the information about the PML cases which they got from Biogen. The FDA could have had the info but the EMEA decided it would go public last Friday. She said, clearly something different is going on in Europe in terms of cases.

As far as her opinion, she essentially said that we are in a wait and see pattern because there just isn't a lot of clinical information/evidence out there. She said she and her fellow neurologists are on top of things -- as a larger community they may have to decide how to proceed--holidays, how long people should be on it, who should be on it-- as more info comes to light as time goes on. She also noted that Biogen is a business so we don't even know if we are getting all info--profits drive Biogen obviously. We don't have much clinical data on the Tysabri holiday idea (how long should you be on the holiday, who should go on it etc.) However, she said that studies show MS activity seems to come back in 6 months when you go off Tysabri. It takes 3 months for the drug to get out of your body. So if she recommended a holiday it would be for 4-5 months (splitting the difference). She initially was against holidays because of the antibody issue. Now she is saying that for someone like me (who didn't have very active or aggressive MS when I started Tysabri) I should consider a holiday. But I'm on #17 and we will reassess at the 24 month mark. She also mentioned that she thought the antibody issue would be less of a problem if you had been on Tysabri for awhile (not a short time 2-4 months) and then go back.

There is more but I can't remember it all right now -- If I remember more I'll post it! There still seems to be a lot of "we just don't know" answers. I feel like I did when I found out I had MS and was asking a million questions about the disease-- "we just don't know."

RW,

Do you know how many people in France are on Tysabri? That's interesting, especially if lots of people are taking it there.

Natalie,

That info actually makes a lot of sense. But I think the 64,000 is about how many patients have taken Tysabri in total (not how many are on it now). The person from Biogen that I spoke to the other day gave me that number as the historical number of patients.

I see my neuro tomorrow so I need to make my list of questions for him.

Thanks for clarifying Wiz. I'm anxious to hear what your neurologist has to say. There are so many unknowns. As my neuro said, the drug has only been on the market for 3 years and we really don't know on a widescale the long term effects after 3 years. So I guess they learn as they go. Suddenly I feel like a guinea pig!!

NMSS Update on Tysabri & PML
 

This update was published 10/29 on the NMSS Home page. It is much more detail than we've had in awhile, and echos a lot of what Natalie's neuro said.

http://www.nationalmssociety.org/new....aspx?nid=2308

More on France, this article is from 2007 when Tysabri was approved in France. They have been infusing since a week before this article was published:

http://www.apmhealtheurope.com/story...46&numero=6296

"...Asked by APM about rapidly evolving MS, Prof de Seze explained that natalizumab can be administered after mitoxantrone, which is limited to six infusions due to toxic haematological effects, but that there must be a time lapse between the two to allow the immune system to recover. He considers it preferable to offer a different immunomodulator after mitoxantrone, or natalizumab before mitoxantrone.
In France, natalizumab can only be prescribed by hospital neurologists. Certain precautions have to be taken before treatment initiation, mostly due to the risk of PML. A brain MRI must have been carried out less than three months previously and neurologists must check for immunosuppression and latent tuberculosis. If previous immunosuppressive treatment has been used, there is a six-month delay before Tysabri treatment can be started, to give the immune system time to recover."

I don't know how many people in France are on Tysabri. They don't seem to be having any of the problems that Germany is having or we would be hearing about it.The patients first infused in France are about where Wiz and I are right now and so far, no PML reported there from any of the information I can find.

The German patients do NOT seem to be having a lengthy washout from mitoxantrone, they do NOT seem to have the monitoring that we have and that France has, and for two countries who started infusing around the same time, the discrepancy in PML cases is outstanding between France and Germany.

As far as the CD4/CD8 testing, it's possible that you get tested as a part of your bloodwork. Ask your neuro exactly what he/she tests for when they do bloodwork as a part of their monitoring.

The Tysabri rate is 60%US/40%ROW as Natalie stated. The figure of 64K is also correct +-. This figure is all patients who have been exposed to Tysabri, including trial patients and people who have discontinued Tysabri. I believe the 45K+- figure is people who are on Tysabri post market retail (since 2006 return to market) and does NOT include trial patients who are in STRATA, TYGRIS, etc. so that is where the discrepancy in the numbers comes from.


My news:
I received a second call from Biogen yesterday. We ARE having an effect. They are being swamped by calls, our points are being presented clearly and the top brass is getting the messages and is listening to the monitored and taped calls.

When asked how long would be too long for them to make a decision as to how to get the information out to patients, I said that people are already speaking with news agencies, calling senators and that suggestions have been made as to more direct protests, including refusing one infusion in one month across the board if need be, but that they do have some time but that shouldn't be construed as more than two to three months.

I reminded him that we as patients are the best advocates for other patients, that Tysabri is a patient driven drug, but that none of us are feeling comfortable right now with what we can tell new people who ask us about our Tysabri experience and that replies are starting to include the fact that we as patients who have been on Tysabri for a long period are being held back by not receiving information about the new cases of PML announced by the EMEA and the FDA, and no word from Biogen and Elan, that our physicians are busy and don't have time to do Biogen's job, that it costs many patients money to see their physician, even if just to ask questions and be given up to date information. I also spoke about the fact that we get faster and more information from financial news agencies than we get from Biogen. I reiterated the fact that we are not asking for names or for people's privacy to be violated, but that we do want country, age, sex, length of time on Tysabri, previous treatments taken, length of washout time, and updates on condition and followups.

I also reminded him that if it wasn't for patients in 2006 at the FDA hearings and working in the background, that Tysabri more than likely wouldn't be on the market right now, and that we did that with little help from Biogen and that with the internet, patients around the world are communicating about this problem and working together to change it.

I'm urging people to continue to call, write letters to any addresses you have for Biogen and Elan, including investor relations, and speak with other Tysabri patients you know, whether they are using the same neuro, infusion center, people you know on Tysabri that you speak with on the net, go to other boards that you know of and get the word out. When speaking to someone personally at Biogen or Elan, please be as polite and professional as possible, state the facts, try to get names, call back numbers and email addresses and share them privately since most emails are not public and we want them on our side in a positive way.

We ARE making a difference here but they need to keep hearing what we have to say.

:grouphug:

All of this is quite frightening, but tysabri has worked so well for Chris that it would also scare me to death for him to take a "holiday" from it.

While I congratulate Biogen for finally saying something, their statement released on the NMSS home page is a disappointment.

They have got to put something in place that gives patients ALL the information they need, not just a general statement full of information that anyone with a computer who searched on this matter since Monday could have found on any investor site or financial news site and also by just reading this thread!!

Deb,

I feel the same way about Tysabri. It's been a miracle for me, and I don't ever forget where I was before and how I got where I am now BUT I am not willing to play Russian Roulette with my life when it comes to information Biogen has but does not share with patients. We need full disclosure of all the details, not just a spoonful of general information.

We just got home and I chose not to get my infusion today. The neuro spoke to me for about an hour. I'm going to go back in three months and talk about whether I want to go back on Tysabri, or go on something else. I'll check back in later with more details. I have another appt this afternoon and won't be home until later on.

That must have been a difficult decision..:hug:

Wiz --- :hug::hug::hug:

I'm ok Barb and Sally, don't worry about me. :) :hug: :hug:

I was thinking about it since last month and after this past week's events with Biogen, it's what I had to do.

He said that a minimum "drug holiday" would be three months since that's how long it takes to clear from your system. He also said he has no way of knowing if this will help or not and anyone who claims to know that it helps is wrong.

He also said that in a post trial evaluation, patients were given spinal taps and that the T cells were at zero even at six months post drug cessation. So we know it keeps doing what it does for a long time. Everyone will be different of course but I'm hoping I'll be about average in that regard.

He also spoke to me about Cladribine, an oral treatment that should be approved in the spring.

It has a long history since it's a chemo drug that has been used for 18 years, but the MS dose is much smaller and even safer. He said the side effects were negligible in the trials. So I'm thinking about that one as a possible replacement. It's hard to believe that a pill is so close to reality. :)

:grouphug: Wiz.

You have a PM, my Tysabri twin.

Hi Wiz, It sounds like you feel good about this decision and have a supportive neuro. I'm sorry you had to make the choice though. Nothing is easy with this disease, is it? :( I'm also a little sad to see you leave the Tysabri board since when I went on the drug you were already here (so in a way, you were with me from the very beginning!!) But I hope things end up going really well for you.

I too have been thinking about Cladribine and also Fingolimod which it sounds like it is not far behind Cladribine in coming out.

Natalie :hug: :hug: :hug:

I'm not going anywhere Natalie. :p :hug: I'm sticking around to keep my thumb on Biogen until they straighten out and behave themselves for everyone else's sake. I might go back on Tysabri anyway, (what if I had a relapse or something)? Who knows what will happen a month from now?

The neuro said he expects that most patients will switch to the oral meds eventually and they'll give the shots and Tysabri a real run for the money as soon as they're released, and I'm anxious to see how that plays out! :) ;)

Good, I'm glad you'll still be around here! I appreciate you pushing against Biogen and the FDA. I've got plans to do some calling on Monday and write to my senator. I'll let you know what happens. I think Biogen is underestimating the pressure of patients right now.

Wiz,
Oh, sweetie, I am sorry to hear you had to go off of Ty:hug:...I know you felt it was helping you...glad to hear Dr. W took time with you...
keep us up to date on how you're doing...and know we're here for ya!!

I asked my neuro if I could possibly have an infusion every 8 weeks instead of every 4 weeks. She said she doubts my insurance will pay for it that way :(

I'm still weak from missing so many infusions this past summer. I've had 2 infusions since then and I am a bit better but I can still tell the difference. My neuro suggested I stay on Ty a little longer while she tries to get more info for me. She said that since I know the risks and the signs of PML and since my QOL was so poor before I started Ty she thinks I should wait a little longer for more info before I stop permanently. She has told me there are several new meds on the horizon.

I started seeing small benefits after my 4th infusion and that was I was leaning less on the wall when taking a shower-therefore, better balance was beginning ;)
Glad no problems with #2:)
Linda

I didn't notice any changes after my first few infusions. My husband noticed them before I did ...LOL He was the first to notice that when I tried to stand up on my own I wasn't as shaky.

Good luck!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!