Evaluating Your Risk of PML
with TYSABRI

What is PML?

Understanding, even pronouncing, progressive multifocal leukoencephalopathy (PML) can be a challenge. Yet, when the words are translated into plain English, their meaning becomes much easier to grasp:

• PML is a "progressive" brain infection, because the damage it causes becomes more severe over time.
• "Multifocal" means multiple locations within the brain.
• "Leuko" means white.
• "Encephalo" means brain.
• "Pathy" means disease.

Simply put, PML is a serious infection of the brain's white matter that usually causes death or severe disability.

What causes PML?

You must have the JC Virus in order to get PML. Some people have it and some don't. While having the JC Virus increases your risk of PML, it doesn't mean you will develop PML.

What's your individual risk of PML?

Although it's impossible to predict if you'll get PML, research findings can help us provide an estimation of your risk based on the following known risk factors: the presence of the virus that causes PML (the JC Virus), the number of TYSABRI infusions (especially greater than 24), and the use of medications, now or in the past, that can weaken the immune system. There may also be other risk factors for getting PML during TYSABRI treatment that we do not know about yet.

What are the signs and symptoms of PML?

While there is currently no known treatment, prevention or cure for PML, you'll need to know how to recognize the signs and symptoms. That way, should you get PML, you may be able to detect it and seek medical attention as early as possible. The symptoms may be very similar to MS relapses. However, PML symptoms do not go away, even with steroid treatment.

Examples of PML symptoms:

• Abrupt or significant personality changes
  These are often noticed by a family member or caregiver.
• Recent or sudden change in cognitive behavior
  Examples include difficulty typing on a keyboard or remembering what time of day it is.
• Unusual difficulty with speech
  Examples include slurred speech, mumbling, speaking in a whisper, or speaking in long, meaningless sentences.
• Other physical changes
  Examples include eyesight, balance, strength, or other problems that have lasted several days.

It's important to monitor how you're feeling. If you notice any symptoms different from the MS symptoms that you typically experience, there is a chance you may have PML. So contact your doctor immediately.

Can an MRI identify PML?

Yes. An MRI is one of the tools that can be helpful in the early identification of PML. Early on, the symptoms of PML can be very mild and difficult to detect clinically. So an MRI is often needed. If you feel that you may be at a higher risk for PML, it may be a good idea to talk to your doctor. He or she may recommend increasing the frequency of your MRIs.

What do you do if you're concerned about PML?

If you (or those close to you) think you may have PML, see your doctor immediately. Your doctor will perform tests to determine if you have PML. Always watch your therapy closely and talk to your doctor about how to identify, monitor and respond to PML as early as possible.

How does Biogen Idec address the risk of PML?

Because of the risk of PML, TYSABRI is only available through a special restricted distribution program called the TOUCH^® Prescribing Program. The goal of TOUCH is to help monitor your safety while taking TYSABRI.

Understanding the JC Virus Test

In our pursuit to learn more about PML, a blood test (the JC Virus Test) has been created to help identify the presence of the JC Virus. This section will help you understand what the JC Virus is, its connection to PML, and how taking the JC Virus Test can help you identify one of the risk factors for PML.

What is the JC Virus?

The John Cunningham Virus, or JC Virus, was first discovered in 1971. It's a common virus, unrelated to MS, that many people have been exposed to, typically in childhood.

In most of these people, the virus is dormant. Most people who are exposed to the virus don't know it or have any symptoms. But for people with weakened immune systems, such as people taking TYSABRI, the virus is able to mutate, spread to the brain, and multiply. This infection (known as PML) causes damage that can lead to symptoms that may be similar to MS symptoms, so it's important to recognize the common signs and symptoms of PML.

How can I get the JC Virus?

As mentioned above, many people have been exposed to the JC Virus, typically in childhood. So, even if you've tested negative for the JC Virus, you should consider taking the JC Virus Test periodically due to 2 factors:

1. Future exposure to the JC Virus
2. False negative test result
   The JC Virus Test is not 100% accurate. A "false negative" result occurs when the test indicates that the JC Virus is not present in your body, when it actually is. This has occurred in a small number of people who have taken the JC Virus Test.

Does the JC Virus put you at a higher risk for PML?

Having the JC Virus doesn't necessarily mean you'll get PML. But it does put you at a higher risk. To determine if you have been exposed to the JC Virus, your doctor may recommend taking the JC Virus Test. Please remember, this test does not diagnose PML, but it can be an important step in assessing your level of risk for PML. An MRI is one of the tools that can be helpful in the early identification of PML.

What does the JC Virus Test consist of?

It's a blood test that can help determine if you've been exposed to the JC Virus. Administration of the test only takes a few minutes. After you've taken it, the samples will be sent to a lab and evaluated, and your doctor should receive your results within a few weeks.

Where can you take the JC Virus Test?

The test is performed at neurologists' offices and labs across the country. You can find out more by talking with your doctor.

How much does the test cost?

In most cases, Biogen Idec covers the cost of the JC Virus Test. If you have any questions about this, please call 800.456.2255 to speak with a TYSABRI ActiveSource™ Coordinator about financial assistance and the TYSABRI ActiveAccess™ Program.

What's your individual risk of PML?

No one can predict who will get PML. However, research findings can help us provide an estimation of your risk based on the following risk factors:

1. The presence of the virus that causes PML (the JC Virus)
2. The number of TYSABRI infusions (especially greater than 24)
3. The use of medications, now or in the past, that can weaken the immune system

1. The JC Virus
   You must have the JC Virus in your body in order to get PML. That's an important point to remember as you review the risk factors for PML. To figure out if you've been exposed to the JC Virus, your doctor may suggest that you take a blood test (the JC Virus Test) before you start or during TYSABRI treatment. After taking the test, you'll get either a positive or a negative result, as seen below:
   

   • Your chance of getting PML increases.
   • Your chance increases even more if you test positive and you have 1 or more of the additional 2 risk factors.
   • Please see below for more information on the 2 other risk factors.

    

   

   • You have not been exposed to the JC Virus.
   • You must be exposed to the JC Virus in order to get PML.
   • However, you may still be at risk for PML due to:
     • The possibility that you can be exposed to the virus in the future
     • The possibility that your test result is a false negative
   • Your doctor may want to re-test you periodically.

    
2. The number of TYSABRI infusions
   If you test positive for the presence of the JC Virus, you should take into account the length of time you've taken TYSABRI. This is because the longer you take TYSABRI (especially longer than 2 years), the higher your chances of getting PML.
3. The use of medications, now or in the past, that can weaken the immune system
   If you test positive for the presence of the JC Virus, you and your doctor should also look at the drugs you've taken (at any time in your life) that can weaken your immune system. Known as immunosuppressants, these drugs include common treatments for cancer and rheumatoid arthritis, but do NOT include some common treatments for MS (such as short-term steroids or Interferons).
   

   NOVANTRONE^®, IMURAN^®, AZASAN^®, RHEUMATREX^®, TREXALL^®, CYTOXAN^®, CELLCEPT^®, MYFORTIC^®

   REBIF^®, COPAXONE^®, AVONEX^®, BETASERON^®, EXTAVIA^®

    
   It's also important to note that even if you do not take any other drugs at the same time as TYSABRI, and you've tested positive for the JC Virus, you could still get PML from past immunosuppressant use.

Estimated risk of PML (for those who test positive)*

This chart provides an estimation of your risk based on the number of TYSABRI infusions you've had and your use of immunosuppressants. Keep in mind that, although TYSABRI has been available since 2006, TYSABRI was studied for less than 4 years. That's why we're not able to include information beyond 48 infusions. It's up to you and your doctor to decide the length of time you should stay on TYSABRI.

*Based on postmarketing PML Data as of September 1, 2011. Data beyond 4 years (48 infusions) of treatment are limited.