Tysabri-PML Cases as of March 1, 2012

I've been following the reported incidence of cases of progressive multifocal leukoencephalopathy (PML) in patients who use Tysabri over the years.  For many months, reports of new cases were found in news publications such as Bloomberg.  However, public reports have been released less and less frequently. 

Biogen Idec has released the latest figures for PML cases and deaths following Tysabri infusions for multiple sclerosis.  The total number of cases have reached 212 PML cases and 46 deaths in Tysabri MS patients as of March 1, 2012.

I have updated the chart on the right to reflect this recent report. This chart is under copyright. Please do not reproduce without permission.

As of March 1, 2012, there have been 212 PML cases, of which 122 have been in the European Economic Area (EU), 80 in the United States and 10 in rest of world (other). 46 of the 212 patients with PML have died.

In 54 natalizumab-treated MS patients who developed PML and in whom serum samples were available 6-187 months prior to the onset of PML, all 54 patients had anti-JCV antibodies detected.

Samples were available from 86 patients at the time of PML diagnosis and all 86 tested positive for anti-JCV antibodies.

In addition, one sample, collected from a patient at the time of PML diagnosis following a cycle of plasma exchange (PLEX) tested negative for anti-JCV antibodies. Because this sample was collected immediately following PLEX, and PLEX removes antibodies from the circulation, the information obtained from this sample is unreliable.

One patient tested anti-JCV antibody positive two months before PML diagnosis. Previously, the patient had tested anti-JCV antibody negative 15 months prior to PML diagnosis, indicating that they had been exposed to the JC virus at some point between the two tests.

Source: Biogen Idec (16/03/12) as shared by Multiple Sclerosis Resource Centre.

I tested negative for the JC Virus

A patient who tests negative for JC virus antibodies and who uses Tysabri may feel like jumping for joy at this negative test result.  However, the the FDA stresses that “patients who test negative for anti-JCV antibodies are still at risk for the development of PML due to the potential for a new JCV infection or a false negative test result.”  It seems obvious that doctors should consider testing patients prior to beginning treatment or during treatment if the antibody status is unknown.  Patients should also consider periodic re-testing for those who previously tested negative for the anti-JCV antibody as a person might later become exposed to the virus.

For the past couple of years, discussions of Tysabri, PML, and the JC virus have been common in the MS community.  Medical professionals have known that a reactivation of the JC virus is responsible for the development of PML in some patients.  But until now there had not been a commercially-available laboratory test which would reliably test for the presence of anti-JC virus antibodies in a person’s blood.  Now available through Quest Diagnostics, the Stratify JCV Antibody ELISA test is manufactured by Focus Diagnostics of Cypress, Calif.  The test is for professional use and by prescription only and is to be performed only at Focus Diagnostics’ Reference Laboratory.


Read this post in its entirety:

The JC Virus Antibody Test Goes Public

Updated Tysabri-PML Cases in September 2011

Investor outlets must be less and less interested in the growing number of multiple sclerosis patients who are taking Tysabri who have developed progressive multifocal leukoencephalopathy (PML).

The reason I say so is that I searched for the August announcement of new cases as reported by Biogen (and previously reported by Bloomberg News).  But there was nothing to be found online.  I even searched for updated information before traveling to Philly last week, but to no avail.

However, a public release of information must have taken place as the NMSS updated their website just last week with numbers reported by Biogen as of September 1, 2011.  See the updated table below.

Occasionally I have received emails regarding these 'monthly' posts regarding PML cases and the accompanying table.  Most of the time, readers simply thank me for giving updates.

Last month I received an email from a 'doctor' who wanted to know where the information came from.  He wanted to know if I had taken the table from an official publication or even a medical journal.  No, I did not reproduce this table from any other source.  I have been meticulously updating this information each month as Biogen, Bloomberg, the FDA, or other official source has given their own update.

I have seen my table reproduced without permission on other websites/blogs.  I was sad to see that credit was not given hence the copyright notification which has been added into the image of the chart.  If you wish to reference this table, please give credit and a link.  It is the proper thing to do.

Thank you.

And to Biogen, please don't make us wait so long for the next update.  You are interferring with my methodical record keeping.  :)

Tysabri-related PML Death Cases Total 29 in July 2011

Five more patients who had developed PML after using Tysabri have died.  Biogen Idec reports that there are 12 more cases of the brain infection, progressive multifocal leukoencephalopathy (PML).  Total cases of PML equal 145 and total deaths equal 29 to date.

Since I was traveling, I missed the announcement of new cases in June and can not find the information published for last month.  However, based on information in this announcement (seen below), we can deduce how many cases there were in June 2011.

Here is an updated table including total of PML cases reported to date:

Here is a chart showing the rate of increase of reported cases of PML and deaths:

The following is the announcement as published by Dow Jones and republished online by the Multiple Sclerosis Resource Centre (MSRC):

12 more cases of brain infection, 5 more deaths in Tysabri MS patients 

Biogen Idec Inc. reported 12 more cases of a rare brain infection occurring in multiple-sclerosis patients taking the drug Tysabri, sold with Elan Corp, bringing the affected patients to 145 as of July 5.

The Weston, Mass., biotech company said there was five more deaths among those patients, bringing total deaths to 29, and provided updated data on its effort to develop a risk-assessment test for the infection. The incidence of the infection -- progressive multifocal leukoencephalopathy, or PML -- is updated monthly and is closely watched.

The drug is considered to be highly effective, but it is mostly reserved for patients that stop responding to other MS drugs or have an aggressive case of the debilitating disease.
Biogen is developing a blood test for antibodies to a specific virus, JC virus, something that may better determine the chances of patients contracting PML.

Many people carry JC virus and it causes no harm, but some biologic drugs that modulate the immune system, including Tysabri, appear to promote activation of JC virus in some patients, leading to PML.

Biogen reported that one patient diagnosed with PML among the latest data actually tested negative for the JCV antibody at the time of diagnosis. The company said the outcome was likely because the test was given after use of plasma-exchange therapy, a process that removes large molecules from the body's blood that accelerates removal of Tysabri and theoretically improving the immune response to PML infection.

The company doesn't know why the patient's physician used the test in that way, a spokeswoman said.

The process of testing newly diagnosed patients -- who by definition should be positive with the JCV antibodies -- is a way of testing the effectiveness of the diagnostic tool. Of those tested, 46 out of 47 were positive at diagnosis.

Among patients with JCV antibody status data from prior to diagnosis with PML, 30 patients that developed the infection previously had the JCV antibodies.

Regulators monitor cases of PML as they occur and have repeatedly said that the benefits of the medicine outweigh the risks. Tysabri was withdrawn from the market in 2005 and relaunched in 2006 -- amid advocacy from patients and physicians that stressed it effectiveness -- with a strict access plan that regularly monitors patients.

The overall global PML rate is now at 1.62 per 1,000 patients. Of the total PML cases, 57 were in the U.S., 81 were in the European Union and seven were in other areas.
The company believes that the best way to assess the pool of PML data shows all patients over a fixed duration range of treatment.

According to that method, the rate is about 1.94 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.54 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year.

For patients on the drug for three to four years, the rate drops to 1.34 patients per 1,000, but Biogen doesn't believe there is enough data to conclude that incidence of the infection drops after a certain amount of time.

Looked at another way, the rate is 2.41 cases per 1,000 patients on the drug for a year or longer, rising to 3.03 per 1,000 for those on the drug for two years or longer, and dropping to 1.85 for more than three years.

Source: Dow Jones Newswires Copyright (c) 2011 Dow Jones & Company, Inc. (15/07/11)

13 more cases of PML in Tysabri patients, 1 more death reported (totals equal 124 and 23, respectively)

Biogen Idec provides the latest information regarding the number of PML (progressive multifocal leukoencephalopathy) cases in multiple sclerosis patients using Tysabri (natalizumab). I am adding below an updated chart detailing the number and location of PML cases, including the number of deaths among those diagnosed with PML.

Out of the 124 reported cases of PML in MS Tysabri patients, 23 patients have died to date. Click for larger image:

Printed below is the press release as published on the Multiple Sclerosis Resource Centre's website:

1 death and 13 more cases of PML in Tysabri MS Patients

Biogen Idec Inc. reported 13 more cases of a rare brain infection occurring in multiple-sclerosis patients taking the drug Tysabri, sold with Elan Corp, bringing the affected patients to 124 as of May 4.

The Weston, Mass., biotech company said there was one more death among those patients, bringing total deaths to 23.

The incidence of the infection--progressive multifocal leukoencephalopathy, or PML--is updated monthly and is closely watched.

Tysabri is seen as a highly effective medicine for the debilitating condition, but it is mostly used for patients that have stopped responding to other MS drugs or have particularly aggressive cases. Biogen is developing a blood test for antibodies to a specific virus, JC virus, something that may better determine the chances of patients contracting PML. The test received CE Mark approval in Europe earlier this year and the companies are conducting large studies of its effectiveness.

Many people carry JC virus and it causes no harm, but some biologic drugs that modulate the immune system, including Tysabri, appear to promote activation of JC virus in some patients, leading to PML.

European regulators recently recommended Tysabri's label include language indicating that JC virus antibody status is a PML risk factor. In the U.S., Biogen and Elan have proposed making a similar change. The U.S. label was updated last month to include the updated incidence of PML. Regulators monitor cases of PML as they occur and have said that the benefits of the medicine outweigh the risks.

Tysabri was withdrawn from the market in 2005 and relaunched in 2006--because of its effectiveness--with a strict access plan that regularly monitors patients. The overall global PML rate is now at 1.44 per 1,000 patients. Of the total PML cases, 49 were in the U.S., 69 were in the European Union and six in other areas. The risk of the infection generally increases with the number of monthly intravenous infusions that a patient receives, but that rate drops after 30 months.

Biogen is studying this apparent decrease, warning that there is limited information from patients on the drug longer than 36 months.

The most-recent data translate to a rate of 2.18 cases per 1,000 patients on the drug for a year or longer, rising to 2.76 per 1,000 for those on the drug for two years or longer, and dropping to 1.6 for more than three years. Looked at another way, the rate is about 1.89 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.49 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year.

Source: ADVFN Copyright 1999-2007 ADVFN PLC (20/05/11)
MSRC http://www.msrc.co.uk/index.cfm/fuseaction/show/pageid/2479

Carnival of MS Bloggers #87

Welcome to the Carnival of MS Bloggers, a bi-weekly compendium of thoughts and experiences shared by those living with multiple sclerosis.

cycles in life and hope

In the span of life

It's the middle that matters

By Mary K. Mennenga

Learning your capable of doing something doesn't mean you should

Time teaches us we aren't as smart as we thought

When we become willing to admit this, that's when growth begins

We no longer need to be told what someone else thinks

The answer to our question is

We begin to seek out the answers for ourselves

To the questions that the answers bring to mind

Creating even more answers that need questioning

As we begin to make decisions about what we believe the truth is

Who we are and what's important to us and why

We learn that each choice we make will change

What choices and options are available to us

It becomes a lifelong cycle of questions, answers

Learning and personal growth making decisions and choices

It's a kind of learning that you learn as you go

So don't judge yourself too harshly

This never-ending cycle helps you become

The person you know you want to be

It's a journey that no matter what you do

Still takes a lifetime to finish

Well coordinated
by Toots of Maybe MS Truth

Today (now yesterday) my masseuse commented that my knickers matched my walking stick. Let me explain.

• a) I have had regular massages since suffering a work related shoulder injury many years ago. I wrenched something. It hurt. A lot.
• b) Unusually for me, these particular knickers are patterned with red cherries.
• c) I own a variety of patterned walking sticks. This is one of two recent bargain buys from Timpsons. It is bizarre how excited I now get about buying new walking sticks. Who’d have thought someone my age would get so much pleasure from a pretty stick! Not a euphemism.

I often coordinate the colours of my clothing and, to a certain extent, accessories – earrings, bags, walking sticks. This probably makes me sound far more fashion conscious than I could ever pretend to be.

Loss of coordination was one of the first symptoms to affect me when I suffered the MS relapse that led to my diagnosis. I don’t remember what I was wearing when I went into hospital (in an ambulance) but I bet it wasn’t in any way coordinated. I do remember I couldn’t write properly with my left hand. I am left hand dominant. Left-handed to you and me.

I had also started dropping things. I was already using a stick due to footdrop, balance and coordination difficulties when walking - and when standing or bending down. Sitting seemed to be ok but that doesn’t take a huge amount of coordination.

None of this is unusual for someone with MS but when you don’t know you have MS and these difficulties are accompanied by visual disturbances, extreme tiredness (fatigue), strange numbness/tingling in limbs and crushing pain round your midriff then the loss of coordination is disturbing. It was the midriff pain that landed me in hospital, It moved up to my chest and the out of hours doctor told me I had to phone 999. Best thing I did. Once in hospital I had the raft of tests that led to my diagnosis.

On diagnosis, I was told by the hospital MS Specialist Nurse that the crushing midriff pain, which felt like a far-too-tight twisting belt, is known as the MS Hug. I think of a hug as a pleasant thing. This wasn’t, and still isn’t, at all pleasant.

One of the problems with all my symptoms is that they didn’t/don’t feel coordinated. To a lay person like me, it’s like having a whole jumble of stuff wrong. So yesterday it was good to be told that one part of me was coordinated. My knickers matched my walking stick. I was well coordinated. Very important, I feel, to look your best... in case you get run over by a bus.

Taken off of Tysabri

by Maryann of MS and ME

These are my two grandsons, Alex (8) and Albert (12). They came, along with their parents, for a visit in March. We had a wonderful time with them. Behind them in the picture is the Roanoke River. We were all walking on the Greenways, a very nice asphalt walkway that goes through Salem and Roanoke.

I had MRI scans of my brain, cervical spine, and thoracic spine taken with and without contrast. Following that, I had a visit with my MS specialist neurologist last week. He said there were no changes since my last MRI. However, in a blood test taken the first of March, I tested positive for the virus that causes PML in people who are on Tysabri. Dr. S told me to discontinue my T infusions for now, but to not have my port removed.

Because of my tiredness, sleepiness and fatigue, he is weaning me off of the Flexeril and Baclofen that I had been taking. If my muscle spasms come back and are too painful, I am to start taking the meds again.

He did a lumbar puncture, which was my second in 20 years. There was a problem gaining entry, and they ended up having me sitting on the exam table, with my arms extended over a walker, and my chin tucked into my chest. That opened the area up and the LP was done. I also had to go to the lab, carrying the fluid from my spine, and have blood drawn.

I will also have a sleep study done because I am overweight and I snore. Then, I will also begin Physical Therapy.

That's an awful lot of stuff. Dr. S seems to think I have another disease along with my MS. He mentioned Primary Progressive MS, and he also mentioned Parkinson's Disease. I hope I'm negative for both of those!

We're going to Margate, NJ to celebrate Passover with Arnie's family. Along the way, we are stopping in Philadelphia to visit a friend I met on Facebook. I am so looking forward to seeing Rita in person, along with her little dog Jake. Can't wait to see the family and be with them for the Seder. This will be a pleasant trip for all of us.

My Shoes. . .

by Jodi Bean

I am wearing a pair of shoes.
They are ugly shoes.
Uncomfortable Shoes.
I hate my shoes.
Each day I wear them, and each day I wish I had another pair.
Some days my shoes hurt so bad that I do not think I can take another step.
Yet, I continue to wear them.
I get funny looks wearing these shoes.
They are looks of sympathy.
I can tell in others eyes that they are glad they are my shoes and not theirs.
They never talk about my shoes.
To learn how awful my shoes are might make them uncomfortable.
To truly understand these shoes you must walk in them.
But, once you put them on, you can never take them off.
I now realize that I am not the other one who wears these shoes.
There are many pairs in the world.
Some women are like me and ache daily as they try and walk in them.
Some have learned how to walk in them so they don’t hurt quite as much.
Some have work the shoes so long that days will go by
before they think of how much they hurt.
No woman deserves to wear these shoes.
Yet, because of the shoes I am a stronger women.
These shoes have given me the strength to face anything.
They have made me who I am.
I will forever walk in the shoes of a woman who has MS.

Author Unknown

I changed the last line of this poem to "who has MS." It was written for another use but rings so true for people living with MS. As a social worker and as a person I try not to be judgmental or to make assumptions about people. I often say to myself and/or co-workers "until I've walked a day in her shoes I'm not going to judge/assume." I think it is a good motto to live by.

I don't know what it is like to live someone else's life. Life is different for everyone. Everyone's journey is different. I walk in my shoes on my journey which has been shaped by MS. I can honestly say that it has greatly impacted everything I do and every decision I now make. But my journey is not a sad journey or an angry journey or even a depressing journey. Yes there are bad days and my future health is unknown. But there are also a lot of good days, great days, happy days, time with family, vacations, time with friends, dinners out, sunny days, good books, funny reality tv shows, laughs, drinks, memories, support, love and HOPE.

My journey is filled with hope. Hope that one day I won't walk my journey in shoes with MS. I hope that one day there will be a cure. I hope that I will continue to be strong and happy and motivated. I hope I will never give up the fight against MS.



This concludes the 87th edition of the Carnival.

The next Carnival of MS Bloggers will be hosted here on May 19, 2011. Please remember to submit a post (via email) from your blog of which you are particularly proud, or which you simply want to share, by noon on Tuesday, May 17, 2011.

Thank you.

Comments for this post.

Tyasbri-related PML deaths holds steady at 20%, 111 total cases of PML reported to date

Although good news has been reported regarding a blood test in development by Biogen which tests for antibodies to the JC virus, the presence of which contributes to the development of PML (progressive multifocal leukoencephalopathy) in patients using Tysabri to treat their multiple sclerosis, a steady stream of bad news regarding cases of PML continues to emerge each month.

This month is no exception.  Nine new cases of PML (a rare brain infection) have been reported in patients using Tysabri.  This brings the total up to 111 patients.  Of those, 22 patients (or 20%) have died.  The condition of the remaining 80% is mostly unknown, however a group of patients and family members affected by PML have gathered in Facebook.

The statistics on the risk of developing Tysabri (which changes according to how many infusions one receives) is as follows:

"The most-recent data translate to a rate of 1.99 cases per 1,000 patients on the drug for a year or longer, rising to 2.5 per 1,000 for those on the drug for two years or longer, and dropping to 1.4 for more than three years." 

The FDA has officially updated the label to include:

• A table summarizing rates of PML with Tysabri use according to the number of infusions (how long the drug is taken or duration of exposure).
• Information on a newly identified PML risk factor. Patients who took an immune system suppressing medication (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate) prior to taking Tysabri have been shown to be at an increased risk for developing PML. The Tysabri label already warned that using immune system suppressing medications at the same time as Tysabri may increase the risk of developing PML.

It is the fact that I have taken and continue to take methotrexate which prevents me from considering Tysabri for myself as a treatment option.  I first learned of this association from other patients in MS forums more than two years ago.  I'm glad that this information has finally been included officially in the labeling of Tysabri.

Please know that I am not anti-Tysabri.  I am in fact pro-medications-which-help.  Tysabri indeed does help many patients.  I just want to let you know the most recent statistics and reports.

Here is the updated chart including April 2011 data which outlines the number of PML cases reported publicly.

The WSJ report is republished below:



9 new cases of brain infection in Tysabri MS patients

Biogen Idec Inc. has reported nine more cases of a rare brain infection among multiple-sclerosis patients taking Tysabri, sold with Elan Corp, bringing the number of affected patients to 111 as of April 1.

The Weston, Mass., biotech company reported that one more of those patients has died, bringing total deaths to 22. The cases of the infection--known as progressive multifocal leukoencephalopathy, or PML--are closely watched as the MS market becomes increasingly competitive.

The drug is generally regarded as highly effective, but mostly used for patients that have stopped responding to other drugs or have aggressive cases of the disease.

Biogen is developing a blood test to test for antibodies to a specific virus, JC virus, something that may better determine the chances of patients contracting PML. The test recently received CE Mark approval in Europe and the companies are conducting large studies of its effectiveness.

Many people carry JC virus and it causes no harm, but some biologic drugs that modulate the immune system, including Tysabri, appear to promote activation of JC virus in some patients, leading to PML.

European regulators recently recommended the label include language indicating that JC virus antibody status is a PML risk factor. In the U.S., Biogen and Elan have proposed making a similar change.

Also recently, the U.S. label was updated to include the updated incidence of PML.
Regulators monitor cases of PML as they occur and have said that the benefits of the medicine outweigh the risks. Tysabri was withdrawn from the market in 2005 and relaunched in 2006--because of its effectiveness--with a strict access plan that monitors patients.

The overall global PML rate is now at 1.31 per 1,000 patients. Of the total PML cases, 46 were in the U.S., 59 were in the European Union and six in other areas.

The risk of the infection generally increases with the number of monthly infusions that a patient receives, but that rate appears to drop after 30 months. Biogen is studying this drop and has warned there is limited information from patients on the drug longer than 36 months.

The most-recent data translate to a rate of 1.99 cases per 1,000 patients on the drug for a year or longer, rising to 2.5 per 1,000 for those on the drug for two years or longer, and dropping to 1.4 for more than three years.

Looked at another way, the rate is about 1.74 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.48 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year.

Source: The Wall Street Journal Copyright ©2011 Dow Jones & Company, Inc (21/04/11) by way of Multiple Sclerosis Resource Centre (MSRC).

7 More PML Infections and 1 More Death in Tysabri Patients; 102 Total PML/Tysabri Patients (March 2011)

This morning I woke up very early cause I had to make my way the hospital for my Rituxan infusion.  Very proud of myself that I was actually up early and could check some email before leaving.  I happened to check my blog stats and noticed that someone at BiogenIdec had been reading my blog posts related to Tysabri/PML patients.

Hmmm, what was going on over at Biogen I thought?  So I conducted a search for newly reported cases of PML and found nothing.  I lurked over at cafepharma and saw that a couple of (anonymous) people were discussing a new total of 102 cases.  I searched for news announcements on Twitter.....nothing came up.  So I left a quick thought around 6am.

After returning home late this afternoon, I find that indeed a brief Nasdaq article had been published this afternoon.  The first version was pulled within 10 minutes (before I could read it) but a corrected version quickly took it's place.  The correction can be found below.

Out of 102 reported cases to date, 42 (41%) have occurred in the United States, 55 (54%) occurred in Europe, and 5 (5%) were elsewhere in the world.  The total number of deaths in the 102 cases is 21 patients representing a 20.6% death rate amongst those Tysabri patients diagnosed with PML (progressive multifocal leukoencephalopathy).

CORRECT: Biogen Reports 7 More Infections In Tysabri Patients

("Biogen: 7 More Infections, 1 More Death In Tysabri Patients," at 4:09 EDT, misstated the regional distribution of cases in the eighth paragraph. The correct version follows:)

By Thomas Gryta
Of DOW JONES NEWSWIRES

NEW YORK -(Dow Jones)- Biogen Idec Inc. (BIIB) reported seven more cases of a rare brain infection among multiple-sclerosis patients taking Tysabri, sold with Elan Corp. (ELN) bringing the total number of affected patients to 102 as of March 4.

The Weston, Mass., biotech company reported that one more of those patients has died, bringing total deaths to 21. The cases of the infection--known as progressive multifocal leukoencephalopathy, or PML--are closely watched as the MS market becomes increasingly competitive.

The drug is generally regarded as highly effective, but mostly used for patients that have stopped responding to other drugs or have aggressive cases of the disease.

Biogen recently halted enrollment in a major clinical trial aimed at testing the earlier use of Tysabri, citing a slower-than-expected pace of finding participants and the desire to devote resources toward "risk stratification" efforts for the drug.

Biogen is developing a blood test that may better determine the chances of patients contracting PML. The test recently received CE Mark approval in Europe and the companies are conducting large studies of its effectiveness.

Regulators have said that they monitor cases of PML as they occur and have concluded that the benefits of the medicine outweigh the risks. Tysabri was withdrawn from the market in 2005 and relaunched in 2006--because of its effectiveness--with a strict access plan that monitors patients.

The overall global PML rate is now at 1.23 per 1,000 patients. A Biogen spokeswoman said the current PML figure is "still generally within what we saw in clinical trials."

Of the total PML cases, 42 were in the U.S., 55 were in the European Union and five in other areas.

The risk of the infection generally increases with the number of monthly infusions that a patient receives, but that rate appears to drop after 30 months. Biogen is studying this drop and warns there is limited information from patients on the drug longer than 36 months.

The most-recent data translate to a rate of 1.87 cases per 1,000 patients on the drug for a year or longer, rising to 2.41 per 1,000 for those on the drug for two years or longer, and dropping to 1.4 for more than three years.

Looked at another way, the rate is about 1.68 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.44 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year.

-By Thomas Gryta, Dow Jones Newswires; 212-416-2169; thomas.gryta@dowjones.com

(END) Dow Jones Newswires
  03-18-111637ET
  Copyright (c) 2011 Dow Jones & Company, Inc.

More Tysabri-Related PML Deaths, Up to 20 Now

The subject of Tysabri and Progressive Multifocal Leukoencelopathy (PML) has begun to receive more and more media coverage in the past couple of months. It was under a year ago that Biogen and Elan (the pharmaceutical companies who make and market Tysabri) stopped giving monthly reports directly to the public.

'They' likely decided that filtering that information through the neurologists (in the TOUCH program) would be wiser, perhaps for them anyways.  Fortunately though, a small group of news media outlets are given the reports to release to the public.  The Wall Street Journal (owned by Dow Jones & Company) has been dutifully providing us with the monthly updates.  A history of the press releases are compiled by the Multiple Sclerosis Resource Centre.

I've written previously about Tysabri and PML, with a lengthier discussion of the topic at HealthCentral.  Use the search box located half-way down the sidebar to find older posts as well.

I'm wondering when somebody is going to finally notice that in one year's time, 60 new cases of PML have been reported.  60!!  Last February the number was 35 and this year it is 95.  The number of deaths have increased in one year from 8 to 20.  That's one death per month on average.

When does this begin to become alarming?  If you read my previous posts, you will notice that I usually do give a non-biased accounting of what Biogen is working on in order to reduce the risk of using Tysabri population-wide.  Trying to identify who is most at risk.

I gotta tell you.  It was the highly-vocal patient activists with superior sleuthing skills who put two-and-two together to notice that many of the earlier cases of PML were in people who had used serious immunosuppressants prior to or in connection with Tysabri.

I would fall into that category of patient since I have used Methotrexate for my RA for almost four years.  Now I use Methotrexate and Rituxan, a drug which also carries the PML risk.  However, in the RA world, we have had only three cases of PML reported out of 100,000 patients.  Only three!!  That information is from October 2009.

I mention Rituxan because I have seen Tysabri patients (who rightfully appreciate what this drug does for them) point out other medications which also carry the PML risk.  But the ratio of risk does not compare.

Another curious difference in this month's Dow Jones news release is that the detail of location of the PML cases is not enumerated.  This had been done each month (except two) since September 2009.  Why did they not include the information this month?

My inkling is that several of the 10 new cases came from within the United States.  (According to chatter on the cafepharma message board, two of the ten were from the United States, but this cannot be confirmed.)  Why do I presume/hypothesize that?  Because as recently as December, even a TOUCH nurse described to me that the vast majority of cases were occurring elsewhere.  This was true one year ago and had become the PR message which Biogen pushed.  It is not true now.

But the US case to EU case ratio of last February, a ratio of 1:2, no longer exists.  The ratio  reached 1:1.2 last month, a number which would be surprising to most US patients.

Now I fully acknowledge that this post does not present a balanced and unbiased discussion of the issue.  I've done that in previous writings.  This time I just wanted to get the information out and provide some personal thoughts on the matter.

Below you will find an updated chart reflecting the newly reported cases.  If I learn how many were in the US compared to elsewhere, I will add that information.

Cases of PML reported in patients using Tysabri, including deaths and locations.

I've included the February 2011 Dow Jones report below.

Biogen: 10 More Infections, 4 More Deaths In Tysabri Patients
By Thomas Gryta, Of DOW JONES NEWSWIRES

NEW YORK -(Dow Jones)- Biogen Idec Inc. (BIIB) disclosed 10 more cases of a rare brain infection among multiple sclerosis patients taking Tysabri, a medication it sells with Elan Corp. (ELN, ELN.DB), bringing the total number of affected patients to 95 as of Feb. 2.

The Weston, Mass., biotech company reported that four more of those patients have died, bringing the total to 20.

The cases of the infection--known as progressive multifocal leukoencephalopathy, or PML--are closely watched as the MS market becomes increasingly competitive.

The drug is generally regarded as highly effective, but mostly used for patients that have stopped responding to other drugs or have aggressive cases of the disease. Sales rose 16% in 2010 to $1.2 billion and 56,600 patients were on the drug at the end of December.

Regulators have said that they watch the cases of PML, but have concluded that the benefits of the medicine to MS patients outweigh the risks. Tysabri was withdrawn from the market in 2005 and relaunched in 2006 with a strict access plan that monitors patients.

There is hope that the development of a blood test may better determine the chances of patients contracting PML. Although the overall risk of the infection remains small, it can have devastating and permanent effects, so a test may make patients and physicians more comfortable with using the drug. Biogen and Elan have filed with the Food and Drug Administration to update the label of Tysabri to include information about certain antibodies in the blood being a PML risk factor.

The overall global PML rate is now at 1.16 per 1,000 patients. Although that is above the typical one-in-1,000 rate commonly cited from clinical trials of the drug, a Biogen spokeswoman said the current PML figure falls within that seen in the trials' confidence interval, a statistical tool that helps show the precision of a measurement.

The rate is about 1.64 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.41 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year. The rate drops to 1.06 per 1,000 patients for those on the drug between three and four years.

-By Thomas Gryta, Dow Jones Newswires; 212-416-2169; thomas.gryta@dowjones.com

Updated PML cases: 79 Tysabri patients diagnosed with PML, 16 have died

Of the available disease-modifying treatments for multiple sclerosis, Tysabri (natalizumab) has arguably been the most controversial to date.  The reason for this controversy is a condition called progressive multifocal leukoencephalopathy or PML.  Any patient who is trying to decide whether Tysabri is the right medication for personal use, she/he must balance the risks and benefits and how those might fit into his lifestyle or circumstances.

Of the 79 Tysabri patients who developed PML, 16 patients have died.

The number of Tysabri patients who have developed PML (progressive multifocal leukoencephalopathy) has reached 79 as of December 17, 2010 says Biogen Idec, Inc.  The company also reports that an additional death among Tysabri/PML patients has occurred, bringing that total number of cases to sixteen.

"The number of PML cases is important because if the infection rate climbs too high, the drug's sales growth may drop. Regulators have said that they watch the cases, but have concluded that the benefits of the medicine to MS patients outweigh the risks.  The overall global PML rate is about 0.96 per 1,000 patients, a company spokeswoman said, which still falls within the 1-in-1,000 rate previously seen in clinical trials and implied on the drug's label. But the rate has been rising, and multiple Wall Street analysts raised concern about the trend on Wednesday as the MS market is becoming increasingly competitive."

Biogen reports that as of Sept. 30, 2010, there are 55,100 patients using the drug around the world and that approximately 75,500 patients have used the drug since its launch.  Of the 79 total cases of PML, 34 cases were in the United States, 40 cases were in the European Union, and 5 cases were in other areas.

"The most recent data update translates to a rate of 1.54 cases per 1,000 for patients on the drug for a year or longer, but rises to 2.05 per 1,000 for those on the drug for two years or longer.  Looked at another way, the rate is about 1.48 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.38 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year."


According to these growing numbers, the death rate of Tysabri/PML patients is at 20%.  I wish that we knew the condition of the other 80% of PML-affected patients.  It would be helpful to know how much PML has permanently disabled them.  Reports are limited.  The chart below shows the number of reported PML cases in patients using Tysabri, where they live, how many have died, and the percentage of deaths among Tysabri-PML patients.




Read this post in its entirety:

Tysabri (natalizumab), PML (progressive multifocal leukoencephalopathy), and Ongoing Research



UPDATE: Biogen announces updated Tysabri/PML statistics.  The total number of cases is now at 85 patients with the addition of 6 new cases reported in January 2011.  The number of deaths holds at 16 patients.  Of the total PML cases, 36 were in the U.S., 44 were in the European Union and five in other areas.

Of the 75 Tysabri patients who developed PML, 15 patients have died to date.

The number of Tysabri patients who have developed PML (progressive multifocal leukoencephalopathy) has reached 75 as of November 2, 2010 says Biogen Idec, Inc.  The company also reports that an additional death among Tysabri/PML patients has occurred, bringing that total number of cases to 15.

"The number of PML cases is important because if the infection rate climbs too high, the drug's sales growth may drop. Regulators have said that they watch the cases, but have concluded that the benefits of the medicine to MS patients outweigh the risks.

The overall global PML rate is about 0.96 per 1,000 patients, a company spokeswoman said, which still falls within the 1-in-1,000 rate previously seen in clinical trials and implied on the drug's label. But the rate has been rising, and multiple Wall Street analysts raised concern about the trend on Wednesday as the MS market is becoming increasingly competitive."

Biogen reports that as of Sept. 30, 2010, there are 55,100 patients using the drug around the world and that approximately 75,500 patients have used the drug since its launch.  Of the 75 total cases of PML, 33 cases were in the United States, 38 cases were in the European Union, and 4 cases were in other areas. 

"The most recent data update translates to a rate of 1.49 cases per 1,000 for patients on the drug for a year or longer, but rises to 1.97 per 1,000 for those on the drug for two years or longer.

Looked at another way, the rate is about 1.49 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.37 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year."

According to these growing numbers, the death rate of Tysabri/PML patients is at 20%.  I wish that we knew the condition of the other 80% of PML patients.  Unfortunately, I do not know the breakdown of the location of the 15 PML-related deaths.


Source: Multiple Sclerosis Resource Centre and  NASDAQ Copyright (c) 2010 Dow Jones & Company, Inc. (18/11/10)

Edited to Add:
The distribution of PML cases and number of deaths reported by Biogen and/or FDA is as follows:
Month reported; Total # PML cases; # in USA, # in Europe, Other; # Deaths
Nov 2010 - 75 total - 33; 38; 4 - 15 deaths
Oct 2010 - 70 total - 29; 37; 4 - 14 deaths
Sep 2010 - 68 total - 28; 36; 4 - 14 deaths
Aug 2010 - 63 total - 25, 34; 4 - 12 deaths
July 2010 - 58 total - 22; 32; 4 - 12 deaths
June 2010 - 55 total - 20; 32; 3 - 11 deaths
May 2010 - 49 total - 19; 27; 3 - 11 deaths
April 2010 - 46 total - ?; ?; ? - 11 deaths
Mar 2010 - 42 total - 15; 24; 3 - 9 deaths
Feb 2010 - 35 total - 11; 21; 3 - 8 deaths
Jan 2010 - 31 total - 10; 19; 2 - 8 deaths
Nov 2009 - 27 total - ?; ?; ? - 5 deaths
Sep 2009 - 24 total - 8; 16; 0 - 4 deaths
July 2009 - 11 total - 3; 8; 0 - 1 death

Here is the Morning Equity Briefing published on Davy Research website regarding the new PML cases and their impact on Tysabri usage.

Elan Corp (ELN US)
Monthly safety update on Tysabri
Jack Gorman
Closing Price: $5.55 Rating: Outperform 30/06/09

FACTS: The latest safety update on Tysabri was released last night (November 16th). Five new PML cases were confirmed during October and this brings the total to 75. Four of the cases were in the US, bringing the total there to 33. There have been 38 cases in the EU and four in the rest of the world. Fifteen of the 75 patients (20%) with PML have died.

ANALYSIS: The new cases have increased the overall incidence of PML in those patients exposed to Tysabri to 0.96 per 1,000 from 0.91 per 1,000. Observing the data by treatment epoch, the new cases look to be in patients with at least 25 infusions.

Distribution of PML patients by treatment epoch has stayed broadly consistent for some months now (note that all data are per 1,000 patients exposed). For 1-12 months, the rate remains at 0.01, indicating little or no PML. For 13-24 months, the rate is 0.37 compared to 0.38 previously. For 25-36 months, the incidence rate remains highest at 1.49, up from 1.44. The 37-48 month increased from 0.93 to 1.01 but remains lower than the 25-36 month cohort.

The data also outline, to 95% statistical confidence levels, what the estimated upper and lower bounds may reach for each of the treatment epochs. There is little change in the mix here and it continues to hover close to 2.0 for the longer durations.

DAVY VIEW: We would not expect that this monthly data will materially change physicians' or regulators’ views on Tysabri’s risk/benefit profile, as there looks to be no sharp increase in either the actual PML rate or the statistical upper bounds of incidence.


UPDATE: Biogen announces updated Tysabri/PML statistics.  The total number of cases is now at 85 patients with the addition of 6 new cases reported in January 2011.  The number of deaths holds at 16 patients.  Of the total PML cases, 36 were in the U.S., 44 were in the European Union and five in other areas.

Tysabri in the News

Yesterday, I took the time to summarize the many news releases and articles surrounding Tysabri which is a disease-modifying drug for MS administered by IV every four weeks.

Read: Tysabri in the News with 24th Case of PML

Also, the NMSS compiled relevant information which is printed below.

Update on Tysabri and PML: Company Releases Details of Cases and Risks

According to information released yesterday by Biogen Idec, there have been 24 confirmed cases of progressive multifocal leukoencephalopathy (PML, a viral infection of the brain that usually leads to death or severe disability) among people who have used Tysabri® (natalizumab, Biogen Idec and Elan Pharmaceuticals) after it became available for prescription in July 2006.

As of the end of September 2009, 60,700 people have used Tysabri worldwide. Although the absolute risk for PML in patients treated with Tysabri cannot be precisely determined, the sponsor has now released data suggesting that the risk increases with increasing time on therapy, starting out lower than the one-in-one thousand level that was estimated at the time of Tysabri’s re-approval in 2006, and rising after two years of infusions to about one in one thousand. There is insufficient information to determine the risk of PML in those who have been on therapy for three years or more. Right now only 2,000 people have been on the therapy for over three years.

This release followed an October 23 announcement from the EMEA, the European equivalent of the U.S. FDA, indicating that one of its advisory committees was launching a review of the risks and benefits of Tysabri in light of the increasing number of new cases of PML.

Signs of PML: Typical symptoms associated with PML progress quickly over days to weeks, and can include:
• personality or behavioral changes
• changes in thinking, memory, and orientation leading to confusion
• onset of seizures, clumsiness or progressive weakness on one side of the body
• disturbances of vision

If individuals taking Tysabri experience new, unusual symptoms, they should contact their prescribing physician immediately. Physicians who need guidelines on the protocol to follow when they have a patient on Tysabri who experiences unusual symptoms should contact Biogen Idec.

Details of Cases: According to the company, the 24 cases of PML have occurred in both men and women who had been given infusions of Tysabri every four weeks for a duration ranging from one year to three and a half years, with an average of two years.

• 16 of the cases occurred in Europe, and 8 in the United States
• 4 of the 24 died
• The degree of disability in the 20 survivors is a wide spectrum: at the milder end, some have recovered enough to return to work, and at the other extreme, some are confined to bed, requiring extensive assistance with activities of daily living, and others were in between this range. Further details of their condition were not provided.
• It appears that when PML is detected and treated early, it generally improves outcomes. It is important that individuals taking this drug and their doctors be vigilant in monitoring for any occurrence of new, unusual symptoms that might indicate PML.
• Based on these cases, the sponsor stressed that, contrary to prior information, the presence of gadolinium-enhancing lesions on MRI does not exclude the possibility of PML. Likewise, the absence of JC virus DNA in the spinal fluid does not exclude PML.
• There has been no characteristic among those who have developed PML that would give substantial clues to who might be more likely to develop it, except that half of the cases had prior histories of having been on immunosuppresive therapies, such as mitoxantrone, and less commonly, azathioprine and methotrexate.
• Right now there is no test that can predict who is more likely at risk for developing PML while using Tysabri; in a large company-sponsored study, testing of blood cells, plasma, serum and urine for the causative JC virus in people before and after 48 weeks of Tysabri therapy (Rudick et al, ECTRIMS 2009) did not show any differences in the presence of the virus in those fluids. The results of these studies, performed at the U.S. National Instituties of Health, differ somewhat from an earlier study (N. Engl. J. Med. 361:1067, 2009) suggesting higher virus levels after treatment.
• When PML was suspected, Tysabri infusions were halted. There is no specific therapy to treat PML, but the best hope is to reconstitute a person’s immune responses. In most of the 24 cases, once PML was confirmed, Tysabri was removed from their systems with the blood-cleansing treatments of either plasma exchange or immunoadsorption.
• During the aftermath of PML, as the immune system begins to recover, a condition called IRIS (immune reconstitution inflammatory syndrome) usually occurs about 4 weeks after the removal of Tysabri from the system. The sponsors suggested that some of the treating physicians found that prompt use of intravenous steroids to treat this brain inflammation led to improvement.

The FDA provides post-marketing safety warnings on Tysabri at this link, although the updated information above is not currently provided.

Carnival of MS Bloggers #43

Welcome to the Carnival of MS Bloggers, a bi-weekly compendium of thoughts and experiences shared by those living with multiple sclerosis.

Yoga, Tysabri, and Insurance

For My Students: Yoga Invocation 
by Nadja

When I teach yoga I like to give freely of myself, to nurture my students and to help bring them closer to their true selves.

Nevertheless, I get as much out of my teaching as they do. Teaching yoga gives me a home, a place of sanity to stand when all I want to do is howl at the moon. It reminds me to breath. It reminds me of my favorite prayer by Saint Francis of Assisi:

"Lord make me an instrument of thy peace
Where there is hatred, let there be love
Where there there is injury, pardon
Where there is doubt, faith
Where there is despair, hope
Where there is darkness, light.
Oh divine master--
Grant that I might not so much seek to be consoled, as to console
To be understood, as to understand
To be loved, as to love
For it is in giving that we receive,
And it is in death to self
That we are born to eternal life."
Amen.

My heart is filled with gratitude for the things I receive from teaching yoga. I bow to my students. I bow to the teacher in all things. I prostrate myself to the divine with the faith that I will find a way no matter what.

Let yoga be your candle in the dark.
Let it lift you and fill you.
Let it in inspire you
Take what you discover on your mat into the world
And create peace, love and harmony.

Tysabri and Little Pieces of My Life
by Azoyizes

At my last neuro appointment, he and I had a talk about how my MS is getting worse and how he and I believe my current therapy (then), Betaseron, just wasn't helping. I told him that I wanted to start Tysabri infusions and he agreed.

Problem is, I have Medicare but no supplemental insurance. The Infusion Center figured that my co-pay would be $575 every four weeks. There is no way in hell that we can afford that kind of money, I don't care how good the drug works.

I contacted TOUCH, and they put me in touch with NORD. I got paperwork from NORD yesterday, and we'll get it filled out and make copies of our financial records, hoping that they will cover my co-pay.

If I do get to go on Tysabri infusions, it will be wonderful. I honestly believe that this drug can help me.

If I don't, I'm not going to get depressed or sad. I will just continue on with my life, deteriorating toward who knows what. I will be DMD-free, anyway.

In other news, I was invited to join a book club--my first ever. Our first book was Travels With Charlie by John Steinbeck. Loved it. We meet every other month at a nice little restaurant that is closed for lunch during the summer, except for the book club. We have great food, good discussions, and lots of laughter. Three of the women in the club (including me) have Saint Francis service dogs. The woman who started the club is also the woman who co-founded Saint Francis. There are 10 of us, and everyone is nice and friendly. Our next book (just started reading it today) is The Good Earth by Pearl Buck. Think I may have read it in high school, 40+ years ago!!

I have also volunteered and been accepted to be on the Outreach/Screening Committee for Saint Francis. Eventually, I will be calling people who have applied for a service dog, asking them questions and talking to them about the responsibilities and hard work that goes into training with your dog. I will sit in on interviews of people who have passed the screening, and I'll have imput into whether or not I believe they would be a good candidate for a dog.

These two things are giving me something to do outside of the house, and also giving me a sense of accomplishment.

Next Saturday is my 40th high school reunion. I am very excited about it. This is the first one I've ever attended. There are a group of us who have kept in touch through the years who are all going to sit at the same table. Next morning, this same group is meeting for lunch and talk. There are so far 45 graduates (plus spouses) who have signed up to come. My class had about 125 people in it, so that's not a bad turnout.

Getting Squeezed
by Lisa of Brass and Ivory

This week I received the annual note from Carefirst BCBS, my insurance company, informing me what my new health insurance premium rate will be for the upcoming 12 months. Of course, I expected that it would go up, no matter how I wished it wouldn't.

What I didn't expect was HOW MUCH it was going up!! 31% increase

OK, so it's not the first time the rate has gone up substantially -
In 2003, it was 22.2%. In 2004, 18.2%. In 2007, 19.9%. In 2008, 18.8%.
(see graph below)

But COME ON. Enough is enough. another 31%?

For insurance which doesn't pay for my MS medications, I will be paying $5172?

That's just for me, no one else, and is not subsidized by any employer since I am self-employed. And unlike most folks who have employer-sponsored health insurance, I will be paying Social Security, FICA, etc taxes on that $5172.

Why doesn't Carefirst cover my main MS medication, Copaxone?

• Because the drug benefit for individual policies is capped at $1500 annually.

How do I get Copaxone if insurance doesn't cover it?

• I have to qualify for assistance from NORD which administers the PAP.

How do I do that?

• I must earn less than 200% Federal Poverty Level (FPL) and can't have significant amounts of money in savings.

How much is 200% FPL?

• This year (2009), it is an Adjusted Gross Income (AGI) of $21,660.

For more on this story, see The Value of Money or Value of Health: What Do You See?

Now, to be fair, the $5172 in insurance premiums will not be 24% of my 'total income.'

Since I'm self-employed, I get to deduct the amount spent on health insurance premiums before income taxes are calculated. So it's a minimum of 19.3%, after Social Security/FICA tax is accounted for and before the AGI is calculated.

But, please tell me. Who can afford to spend 19-24% of the highest level of income they can afford (or are allowed) to earn for health insurance premiums?

And let's just say that for 2008 I did earn considerably less than 200%. In fact, $5172 really would be closer to, if not more than, 25% of total income.

According to proposed health care reform legislation, affordable premium rates for someone with my income level would be closer to 5% of income AND I would very likely have coverage for my medical needs, including pharmaceuticals.

A few weeks ago, I sat down and calculated what medical expenses were included during one year in obtaining the routine care I require. That detail can be read at Living with Multiple Sclerosis: The Cost of Chronic Illness.

Update: Now it looks like the Public Option just might get dropped during negotiations in Congress. sigh.


This concludes the 43rd edition of the Carnival.

The next Carnival of MS Bloggers will be hosted here on September 10, 2009. Please remember to submit a post (via email) from your blog of which you are particularly proud, or which you simply want to share, by noon on Tuesday, September 8, 2009.

Thank you.

Comments for this post.

WSJ reports - Elan CEO Defends Tysabri Sales, Citing 'Good Progress'

Elan CEO Defends Tysabri Sales, Citing ‘Good Progress’

By Jeanne Whalen
December 19, 2008 @ 3:06 pm

Elan is looking forward to the end of 2008. A slew of disappointments have grounded the biotech company’s once high-flying shares; they’ve fallen more than 70% this year.

Shareholders are grumbling, including one big one who is so fed up that he’s called for the ouster of CEO Kelly Martin.

As a snowstorm hit Health Blog HQ today, Martin braved the weather to come by, defend his record and talk about how he’s trying to turn things around.

First, Tysabri, the multiple sclerosis treatment Elan sells with Biogen Idec. The drug will have sales of nearly $1 billion this year. Sounds great, right? Blockbusters are hard to come by these days. But some shareholders think sales should be a lot brisker, given Tysabri’s efficacy advantage over other drugs.

Female MS Patient in the US dies from PML after 14 months on Tysabri.

I return from Christmas shopping and find this news bit (from Bloomberg Health New). My heart goes out to this patient's family.

If I remember correctly, this woman began experiencing symptoms of PML in September (information based on a comment left on Kim Fabrizio's blog).


Biogen, Elan Shares Fall After U.S. Tysabri Patient’s Death

By Elizabeth Lopatto

Dec. 19 (Bloomberg) -- Shares of Biogen Idec Inc. and Elan Corp. fell after Biogen said a multiple sclerosis patient who developed a severe brain infection after taking the drug Tysabri has died.

Biogen declined $1.26, or 2.6 percent, to $46.75 at 4 p.m. in Nasdaq Stock Market composite trading. Elan fell 35 cents, or 7.9 percent, to close at 4.10 euros in Dublin trading.

Cambridge, Massachusetts-based Biogen was informed of the American woman’s death two days ago, company spokeswoman Naomi Aoki said in an interview. The company reported on Oct. 29 that the patient had been diagnosed with the brain illness, progressive multifocal leukoencephalopathy. The death is the first among four cases of the brain illness reported since Tysabri was reintroduced in the U.S. in 2006.

“Given the expected negative attention that this death will attract in the medical literature and media, we believe there is increased risk to owning shares of both Biogen and Elan,” wrote Christopher James, an analyst for Rodman and Renshaw, in a note to investors.

Tysabri generated $597 million in sales in the first nine months of the year. It is Biogen’s second-best-selling medicine after the MS drug Avonex. Biogen and its marketing partner, Irish drugmaker Elan, pulled Tysabri from the market in February 2005 after three patients, two of whom died, contracted PML.

The patient had received 14 Tysabri infusions before becoming ill, Biogen reported in a regulatory filing in October. Aoki declined to comment on the type of treatment for PML the patient received.

Since Tysabri’s reintroduction, three European patients have contracted PML. Biogen and Elan reported one case on Dec. 15 and two others on July 31.

48,000 Patients

More than 48,000 patients have taken Tysabri, Biogen told investors on Oct. 21, when the company released its earnings. Chief Executive Officer James Mullen said 100,000 patients will be taking the drug by 2010.

PML is included in Tysabri’s prescribing information as a possible side effect in 1 of every 1,000 patients taking the drug. The condition occurs when the JC virus, named with initials for the first patient diagnosed with it, evades the body’s immune defenses and penetrates the brain, causing irreversible damage.

The U.S. Food and Drug Administration approved Tysabri’s return to the market in June 2006 because research showed the treatment is twice as effective as other MS drugs. At the same time, the agency mandated strict measures to monitor side effects.

Neurological Disorder

MS is a neurological disorder that robs people of muscle control and balance, sometimes leading to damaged vision and paralysis. The disease, which affects about 2.5 million people worldwide, is caused when the body’s immune system attacks the protective coating of nerve fibers.

Tysabri, given intravenously once a month, is designed to suppress the immune assault and is one of five immune-suppressing therapies that are known to cause PML. The others are Roche Holding AG’s CellCept, Biogen and Genentech Inc.’s Rituxan, Genzyme Corp.’s Campath and Genentech’s Raptiva.

To contact the reporter on this story: Elizabeth Lopatto in New York at elopatto@bloomberg.net

Last Updated: December 19, 2008 16:21 EST

**********
Another version of the same story:

Biogen says Tysabri PML patient dies in U.S.

Fri Dec 19, 2008 4:52pm EST
By Toni Clarke

BOSTON (Reuters) - Biogen Idec Inc said on Friday that a multiple sclerosis patient who had been diagnosed with a rare brain infection while taking its drug Tysabri has died, sending the company's shares down nearly 3 percent.

Biogen and its partner Elan Corp Plc disclosed the case in October. Naomi Aoki, a spokeswoman for Biogen, said the company learned of the patient's death earlier this week.

Tysabri is seen as crucial to the growth of both companies. The drug was temporarily withdrawn from the market in 2005 after it was linked with a rare brain infection known as progressive multifocal leukoencephalopathy, or PML.

The drug was reintroduced in July 2006 with stricter safety warnings.

So far, there have been four new cases of PML, an infection rate that is still less than the one in 1,000 warned of in the drug's label. Nearly 18,000 patients have received at least a year of Tysabri. But investors are watching to see if the rate increases, and they are also looking at how successfully patients can recover.

"While we continue to believe the benefit/risk profile of Tysabri as favorable, we believe this death could lead the FDA and physicians to alter how future PML cases are managed," said Christopher James, an analyst at Rodman & Renshaw.

The patient who died was a United States patient who had received 14 monthly infusions of Tysabri as a stand-alone treatment. Previously she had received other therapies.

After developing the brain infection, the patient was treated with a procedure known as plasmapheresis, in which blood is removed, cleared of the drug, and replaced.

While the U.S. patient died, two patients who developed PML in Europe, and whose cases were announced in July, appear to be recovering following treatment, even though one had not been expected to survive. Earlier this month, Biogen announced that a fourth patient had developed PML. This patient, in Europe, is still alive.

The European patient that had not been expected to survive had developed a condition known as immune reconstitution inflammatory syndrome, or IRIS. This occurs when the immune system, in eliminating an infection, produces an excessive inflammatory response that can worsen symptoms.

The patient was treated with corticosteroids.

Geoff Meacham, an analyst at J.P. Morgan, said it seems likely the U.S. patient, having gone through plasmapheresis, died of IRIS, and that since the European patient recovered, it might be possible to manage IRIS using steroids and close monitoring. Biogen declined to confirm this theory, citing patient privacy.

"In our view, the rate of PML is now critical to assessing the launch trajectory, and the regulatory outlook, should it stay in the 1/1000 range," Meacham said in a research note.

© Thomson Reuters 2008. All rights reserved.

Tysabri in the News AGAIN!! Is the fear machine working overtime?

Thomson Financial News

UPDATE 2-Biogen says new brain infection linked to Tysabri
12.15.08, 12:51 PM EST
By Ransdell Pierson

NEW YORK, Dec 15 (Reuters) - Biogen Idec Inc (nasdaq: BIIB) said on Monday it notified regulators of a new case of a potentially deadly brain disease in a patient being treated with its Tysabri multiple sclerosis drug, the fourth such case reported globally this year.

The latest case of the brain infection, known as progressive multifocal leukoencephalopathy (PML), was seen in a European patient who had been taking Tysabri as a stand-alone treatment for 26 months, Biogen said in a regulatory filing.

'The patient is under physician's care,' company spokeswoman Shannon Altimari said, noting it was too soon to speculate on the prognosis for the patient.

Biogen shares were off 1.3 percent in midday trading, while the stock of its marketing partner, Elan Corp (nyse: ELN) of Ireland, fell 4.2 percent on the New York Stock Exchange.

Shares of Biogen and Elan fell sharply after the drugmakers disclosed on Oct. 29 that a case of PML had been seen in a U.S. patient. In July, the companies reported two cases had emerged in Europe.

This year's four cases of affected patients, all still alive, are the first to be announced since Tysabri was withdrawn from the market in 2005 after three earlier patients developed the brain infection. Two of the earlier three patients died.

Asked why no cases were seen in 2006 or 2007, Biogen spokeswoman Naomi Aoki on Monday said, 'The drug had been taken off the market for a little over a year, and returned in July 2006.'

She said Biogen and Elan believe the superior effectiveness of Tysabri in preventing relapses of multiple sclerosis symptoms justifies its use, despite the relatively low risk of PML.

68 PCT RELAPSE REDUCTION

Aoki said more than 35,500 patients worldwide are taking Tysabri, and that the drug in clinical trials was able to produce a 68 percent reduction in relapses.

Rival drugs, by contrast, are able to reduce relapses by only about a third, she said.

Tysabri's package insert label cautions that patients taking the drug have a 1-in-1,000 risk of developing PML, but the overall incidence of the brain infections seen so far is 'still well within' that magnitude, JP Morgan analyst Geoffrey Meacham said in a research note.

'Overall, we would characterize this new case as completely in line with expectations at this point,' Meacham said, noting that the infrequent occurrence of PML suggests there is little risk Tysabri will again be pulled from the market.

Third-quarter sales of Tysabri rose 18 percent to $171 million, a slowdown from the 25 percent growth seen in the second quarter. Biogen said growth was tempered as doctors continue to assess the drug's risks versus its benefits.

Even so, Biogen in October reaffirmed it expects 100,000 patients to be taking Tysabri by 2010, a near tripling of the current patient roster. The company on Monday said its ambitious goal remains in place.

Multiple sclerosis, a so-called autoimmune condition that can cause progressive paralysis of limbs, occurs when an overactive immune system attacks the protective myelin sheath around nerves.

Autoimmune drugs work by taming the immune system, but in doing so some of them can leave the body prey to infections that rarely affect the general population.

Aoki said a handful of other drugs, including Biogen's own Rituxan treatment for cancer, carry warnings of increased risk for PML.

Copyright Thomson Reuters 2008. All rights reserved.

Reports of Suspected PML in Tysabri Use - Not Alarming

Ever wonder how investors view news articles and MS patients in general? Or how often do you consider that online conversations are being monitored?

Read - Suspected PML Cases for Biogen/Elan MS drug (Tysabri) Not Alarming

Calling all Tysabri Patients - Informal Project Underway

Hi All,

I'm approaching all patients who use Tysabri to help me with a little project. 

I'd like to collect some basic information regarding the costs associated with Tysabri infusions and the amounts which are actually paid for those infusions. These are the things I'm interested in learning.

What is the original amount billed to your insurance company (or yourself) for:

a) Infusion location/services

b) Tysabri medication

What is the amount which your insurance company allows to be charged (paid) for:

a) Infusion location/services

b) Tysabri medication

What is your actual co-pay (out-of-pocket costs) required for:

a) Infusion location/services

b) Tysabri medication

Where do you receive your infusions?

Neurologist office, Stand-alone Infusion Center, or Hospital Facility

In which state to you receive your infusions?

To answer the first three questions you will need to locate a recent EOB (Explanation of Benefits) which you should have received from your insurance company. The information should be found on that form.

I thank you so much for helping me with this informal project. Please leave a comment or email me directly.

Thanks so much. I look forward to your responses.

-Lisa

Two New Cases of PML in MS Patients Taking Tysabri

UPDATE FROM NATIONAL MS SOCIETY:

Aug 01, 2008

Two New Cases of PML Develop in People with MS Taking Tysabri

Biogen Idec and Elan Pharmaceuticals informed drug regulatory authorities about two new confirmed cases of PML in individuals who were taking Tysabri® (natalizumab) as a monotherapy (not in combination with other therapies). PML (progressive multifocal leukoencephalopathy) is a viral infection of the brain that usually leads to death or severe disability. Although FDA prescribing information includes a black box warning about the risk of PML, the three previous cases of PML that occurred in the context of clinical trials were in patients who had taken Tysabri in association with other immune-modulating or immune-suppressing medications.

Details: The companies held a conference call for prescribers and investors to provide details about the two cases, both of which occurred in European males. One had received Tysabri as a first line therapy because of the aggressive nature of his disease, and had been on Tysabri alone for 17 months before developing a slowly progressive focal twitching and weakness in one arm. Brain MRI showed a non-typical lesion but his spinal fluid was negative for JC virus until it was done a second time. He received five courses of plasma exchange and is currently stable and at home.The second case has been reported to be a male who had received immune-suppressing and immune-modulating therapies in the past. He used Tysabri alone for 14 months before developing weakness on one side of the body. Despite treatment with steroids his symptoms progressed and included cognitive changes. His MRI was not typical for MS, and spinal fluid was positive for JC virus. He is reported to be hospitalized and is slated to receive plasma exchange therapy.

Background: Tysabri is a laboratory-produced monoclonal antibody. It is designed to hamper movement of potentially damaging immune cells from the bloodstream, across the "blood-brain barrier" into the brain and spinal cord. It has been shown to be effective in reducing the risk of disability progression and exacerbations (relapses).

In the United States, the drug is available only through a risk management program called TOUCH, and is only available through doctors and infusion sites enrolled in the program. The program is designed to monitor patients for possible signs of PML and other serious opportunistic infections. Separate risk management plans are also in place in individual countries in Europe.

The companies recently reported that nearly 32,000 patients have been dosed with Tysabri. Of those, nearly 14,000 have been on the drug for at least 12 months, and 6,600 have been on the drug for at least 18 months. Up to this time there have been no previous confirmed cases of PML in patients using the drug as monotherapy.

Recent, small-scale studies supported by Biogen Idec have investigated the use of plasma exchange, a blood-cleansing treatment, to clear the bloodstream of Tysabri in the event of PML, for which there is no established therapy. The studies suggested that plasma exchange could indeed clear much of the drug from a person's bloodstream, but it was not possible to determine experimentally whether that would lead to a reduction of PML symptoms.

Comment: These incidents of PML are unfortunate and disappointing, and we hope for the best possible outcomes for these individuals and their families. However, their occurrence is within range of the predicted frequency of PML cases, estimated by a published report and by the FDA, of approximately 1 in 1,000 people taking the drug. "We are encouraged that the risk management plans in place for early surveillance, such as the TOUCH program in the U.S., are doing the intended job of identifying possible cases of PML early so that patients can be treated quickly," said John R. Richert, MD, executive vice president of research and clinical programs at the National MS Society . "It will be important to observe whether plasma exchange therapy in these new cases will have an ameliorating effect on their PML."

These incidents highlight the need for individuals taking Tysabri to be sensitive to any occurrence of new, unusual symptoms and to contact their prescribing physician or infusion nurse immediately if they occur. Signs of PML may include any new or worsening neurological symptoms such as any changes in thinking, eyesight, balance, strength and other symptoms.

Tysabri is a registered trademark of Biogen Idec and Elan.

The National MS Society is proud to be a source of information about MS. Our comments are based on professional advice, published experience and expert opinion, but do not represent individual therapeutic recommendation or prescription. For specific information and advice, consult your personal physician.

Biogen and Elan report Tysabri brain disease cases

By Deena Beasley and Bill Berkrot
Reuters, published August 1, 2008

LOS ANGELES/NEW YORK: Biogen Idec and Elan have notified regulators of two new cases of a potentially deadly brain disease in multiple sclerosis (MS) patients being treated with Tysabri.

Biogen shares dropped about 23 percent in after-hours trading, while Elan's shares fell 45 percent in New York.

"This is going to have very broad, very wide ramifications for the commercial prospects of the drug because there's just a lot of uncertainty here," said Cowen & Co analyst Eric Schmidt.

Tysabri, co-marketed by Ireland's Elan and Cambridge, Massachusetts-based Biogen, was withdrawn from the market in 2005 after three patients developed the brain infection known as progressive multifocal leukoencephalopathy (PML).

The drug returned to the market in 2006 with warnings after the U.S. Food and Drug Administration decided MS patients willing to accept the risks should be able to have access to the drug's potential benefits.

The two new PML patients, one of whom is hospitalized, are in the European Union, the companies said.

More cases are likely and physicians are likely to reduce the number of patients they start on the drug as they are reminded of long-term potential safety issues, Morgan Stanley analyst Steven Harr said in a research note.

Elan and Biogen said more than 31,800 patients were being treated with Tysabri as of the end of June and second-quarter sales totalled $200 million (100 million pounds).

"We've said all along, and the FDA has also stated and it's clearly outlined in our label that we expect to see additional cases of PML," Biogen spokeswoman Naomi Aoki said. "These are the first cases we've seen since the reintroduction in the U.S. and approval in Europe two years ago."

She said the company believes that heightened clinical vigilance has been the best way to monitor for PML and that heightened vigilance was critical in identifying these cases.

Schmidt said, the "key fear factor in the market place is going to be what happens when you treat beyond two, two and a half years ... Nobody knows the answer and that's kind of scary."

"I think you'll see a general pause in the market place, especially in the U.S., where safety has become more of a lightning rod issue, in part driven by the litigious nature of our society," the analyst said.

Tysabri also won U.S. approval this year to treat adults with moderate to severe Crohn's disease who have had a poor response to, or cannot take, other therapies.

Shares of Biogen, which closed at $69.76 on Nasdaq, fell to $53.68 after hours, while shares of Elan, which closed at $20.05 on the New York Stock Exchange, were trading at $11.00.

Elan's shares had already lost one-third of their value on Wednesday when investors sold the stock after disappointing data on an experimental Alzheimer's drug Elan is developing with Wyeth.

Biogen and Elan have a scheduled a conference call with analysts and investors for Friday morning.

(Reporting by Deena Beasley and Bill Berkrot; editing by Jeffrey Benkoe and Carol Bishopric)

Biogen Idec and Elan Corporation, plc
Host Conference Call For Investment Community

Date: Friday, August 1, 2008
Time: 8:30a.m. ET
Length: 1 hour

Listen to Webcast here


Below is the report filed with the SEC on July 31, 2008.

Item 8.01 Other Events.

On July 31, 2008, Biogen Idec Inc. and Elan Corporation, plc notified relevant regulatory agencies of two confirmed cases of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with TYSABRI in the commercial setting. Additional information about these cases is set forth below.

Case 1

	•		On July 30, 2008, following a period of clinical evaluation, Biogen Idec received confirmation of a diagnosis of PML in a MS patient in the European Union (EU).
	•		The diagnosis was made based upon the detection of JC Virus (JCV) DNA in the cerebrospinal fluid (CSF) in the setting of clinical signs, symptoms and magnetic resonance imaging (MRI) findings consistent with the diagnosis of PML.
	•		As reported to the company on July 31, 2008, the patient remains clinically stable and ambulatory at home.
	•		Background:

	-		Patient in EU with aggressive MS who was naïve to prior disease modifying therapy;
	-		TYSABRI monotherapy for approximately 17 months;
	-		Clinical vigilance led to early identification of signs and symptoms of possible PML and medical work-up which included MRI scanning and CSF testing, but PML was not confirmed at that time;
	-		However, given continued clinical suspicion by treating physician plasma exchange was initiated as outpatient;
	-		Subsequent testing of CSF detected JCV DNA which was reported to the company on July 30, 2008;
	-		It was then determined by PML experts that the latest CSF results together with the clinical history, physical findings, and MRI results are consistent with the diagnosis of PML.

Case 2

	•		On July 31, 2008, Biogen Idec was notified of a diagnosis of PML in a second MS patient in the EU.
	•		The diagnosis was made based upon the detection of JCV DNA in the CSF in the setting of clinical signs, symptoms, and MRI findings consistent with the diagnosis of PML.
	•		As reported to the company on July 31, 2008 the patient is currently hospitalized.
	•		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;
	-		Evaluation for possible PML included MRI scanning and CSF testing;
	-		CSF testing detected JCV DNA, which was reported to the company on July 31, 2008;
	-		The CSF results together with the clinical history, physical findings, and MRI results are consistent with the diagnosis of PML.