[lady_express_44]

For those who don't follow the Tysabri thread, RW announced the 7th patient with PML had been discovered in Europe:

Originally Posted by Riverwild

For those who have not yet heard, Biogen filed another 8K this morning about another case of PML. I don't have any confirmed details yet, and will post when I know more.

This is what I have from a neuro:
"I haven't heard anything more about the case than is on the 8K. This patient was monotherapy for 26 months and in the EU. This patient's PML is confirmed using accepted definitions of positive PCR in individual with consistent MRI and history. Clinical vigilance seems to have caught this one early as well. FWIW, the last time I got an update, patient 1 (Sweden) was doing well and at home, Patient 2 (Germany) was still in ICU but able to be extubated and able to communicate some (expect permanent sequelae), Patient 3 (US -Florida?) was discharged and doing well. Haven't yet heard what symptoms this patient had. "

Also, the 6th patient (or 3rd since the re-introduction of the drug), from the US, has died recently:

Originally Posted by lady_express_44

UPDATE:Patient On Biogen, Elan MS Drug Dies Of Brain Disease

DOW JONES NEWSWIRES

By Thomas Gryta
Of DOW JONES NEWSWIRES

NEW YORK (Dow Jones)--A multiple sclerosis patient being treated with Tysabri, from Biogen Idec Inc. (BIIB) and Elan Plc (ELN), has died of a previously disclosed occurrence of a rare brain infection.

Biogen originally reported the confirmed case of progressive multifocal leukoencephalopathy, or PML, in late October. Tysabri, key to the future growth of both companies, is very effective in fighting MS, but a suspected link to PML led to its withdrawal from the market for 18 months beginning in 2005.

Patients on the drug are now closely monitored and four cases of the often fatal infection have occurred since its July 2006 relaunch, but the death may quell hope that PML could be a treatable side effect of the drug.

Shares of Biogen were recently down $1.15, or 2.4%, to $46.86, while Elan dropped 32 cents, or 5%, to $5.96.

The patient who died was the third case and the only one in the U.S. The other three are in Europe and remain alive.

A Biogen spokeswoman said that the company was informed earlier this week of the death and wouldn't disclose more information out of respect for the patient and her family.

The patient received 14 monthly infusions of Tysabri as a monotherapy and was previously treated with Teva Pharmaceuticals Industries Inc.'s (TEVA) Copaxone, Bayer AG's (BAY.XE) Betaseron and Biogen's Avonex. She also took methotrexate for a rheumatolgical condition.

All of the patients that developed PML were given plasmapharesis, a process that removes large molecules from the blood, speeding up Tysabri's removal and allowing the immune system to fight the PML infection.

When the drug is removed from the system, patients often experience an inflammatory response as the immune system reconstitutes itself, which can lead to their condition getting worse before any improvement is seen.

The death of the patient may temper arguments that the intricate distribution and monitoring program used for Tysabri, and use of plasmapharesis may ease the risk of PML for patients. Biogen has hoped that PML could eventually could be a "survivable adverse event."
But given the severity of PML, some believe that the death of a patient shouldn't be a surprise.

"We think the odds of surviving PML are still better than initially thought," said analyst Geoffrey Meacham of JPMorgan.

Tysabri's label implies that one in every 1,000 patients could get PML, but the actual number remain well below that ratio. As of Sept. 30, more than 35,500 patients use Tysabri, with 9,500 patients on it for at least 18 months and 3,700 for more than two years.

Steven Harr, an analyst with Morgan Stanley, writes that the recent death may demonstrate that Tysabri's risk is consistent with the label, to the disappointment of some investors and physicians that thought it might actually be lower.

-By Thomas Gryta, Dow Jones Newswires; 201-938-2053; thomas.gryta@dowjones.com

http://www.djnewsplus.com/article/DN...Brain+Disease+

The ratio of PML cases now appears to be 7:9500 (or 1:1357), for those who've been on it for 18+ months. Still slightly less than the 1:1000 they predicted.

Cherie

[ewizabeth]

The ratio of PML cases now appears to be 7:9500 (or 1:1357), for those who've been on it for 18+ months. Still slightly less than the 1:1000 they predicted.

The thing is that most patients are not monitored closely enough, according to my neuro. He comes in and speaks with me every month. They're very careful at his office. Many patients don't see a doctor each month and that troubles him. It troubles me too because they need to watch for signs of PML looming. It shouldn't just be a cash grab for the doctors and centers infusing it.

I had my 21st infusion today and he gave me the news of the most recent death.

[lady_express_44]

Originally Posted by ewizabeth

The thing is that most patients are not monitored closely enough, according to my neuro. He comes in and speaks with me every month. They're very careful at his office. Many patients don't see a doctor each month and that troubles him. It troubles me too because they need to watch for signs of PML looming. It shouldn't just be a cash grab for the doctors and centers infusing it.

I had my 21st infusion today and he gave me the news of the most recent death.

It is clearly still a better risk than they predicted, at least so far, so I don't see why this news would scare people into a different decision.

And I agree that people are probably being watched like hawks, especially as the number of cases increases. The ratio of 1:1000 was predicted for over 18 months of use, and we are getting to the point where there are a fair number who are reaching that timeline now . . . so no doubt the doctors will be more vigilant and/or hyper-sensitive to any news that comes out over the next 6 -12 months.

Originally it was thought that this Florida woman was sent home and doing ok, but then she dies! To date no one has died post-marketing, so I think they hoped that that wasn't going to happen if it was caught quickly enough under TOUCH safety protocol.

There are only 9500 who've been on it long enough (and a large % of those were in the trials), and who've come down with PML . . . so I don't think they claim to have any clear patterns emerging. At this point it seems to be luck of the draw whether we will get PML, and/or whether we will live through it.

But, like I said, everyone on it already accepts that risk.

Cherie

[dmplaura]

"Biogen has hoped that PML could eventually could be a "survivable adverse event." "

^^ This line REALLY bothered me from the article. 'Adverse event'? You kidding me? It's almost like they're downplaying the severity of PML... at least that's what I took home from their choice of words.

[marcstck]

My neuro insists that all of his patients on Tysabri undergo a spinal fluid analysis every six months, in an attempt to detect activated JC virus.

He's pulled a number of patients off of the drug who have come up positive for the activated virus but had not yet developed PML.

I'm on Rituxan, another drug associated with PML. I should be scheduled to have a spinal tap for spinal fluid analysis purposes sometime in the next few weeks...

[ewizabeth]

Originally Posted by dmplaura

"Biogen has hoped that PML could eventually could be a "survivable adverse event." "

^^ This line REALLY bothered me from the article. 'Adverse event'? You kidding me? It's almost like they're downplaying the severity of PML... at least that's what I took home from their choice of words.

Apparently it is "survivable" if you have HIV or AIDS but not in this situation? (I remember reading that somewhere I think or my neuro told me.)

It isn't really something you recover from, not like you can go back to any semblance of your life before PML in these cases, if you happen to survive.

[lady_express_44]

"Survivable adverse event" doesn't sound as tuned out as "treatable side-effect" . . .

"Patients on the drug are now closely monitored and four cases of the often fatal infection have occurred since its July 2006 relaunch, but the death may quell hope that PML could be a treatable side effect of the drug."

Like Wiz said, it's not like a person has a chance of EVER recovering from the damage that PML causes . . .

Cherie

[Harry Z]

He's pulled a number of patients off of the drug who have come up positive for the activated virus but had not yet developed PML.

While this doc should be commended for following his patients so closely we know that he would be in the minority at this level of concern. What is disturbing is the fact that he has stopped givng Tysabri to several of his patients who are showing activated levels of the virus. You start to wonder how many other patients may be in this category and don't know it!

Harry

[dmplaura]

Has the notion of testing spinal fluid in those taking Tysabri come into discussion as part of the TOUCH (or whatever) programs?

It would only make sense to me that IF looking for a pre-cursor to PML is possible in the spinal fluid, that this be part of the routine of monitoring.

(I know nothing about the background of Tysabri, but I'm just shooting this one out there for perhaps someone to respond to, because now I'm curious!)

[marcstck]

Originally Posted by Harry Z

While this doc should be commended for following his patients so closely we know that he would be in the minority at this level of concern. What is disturbing is the fact that he has stopped givng Tysabri to several of his patients who are showing activated levels of the virus. You start to wonder how many other patients may be in this category and don't know it!

Harry

Here's a link to a PDF my neurologist's research on this issue. It should be of great interest to those following the Tysabri saga...

http://msrcny.org/pdfs/JC-BK_virus_in_MS_4-08.pdf