Tysabri: Shutting Down MS Activity Presented at the patient symposium 10282007

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Tysabri Shutting Down MS ActivityPresented at
the patient symposium 10/28/2007

• Armistead D. Williams III MD
• Attending Neurologist, IMSMP
• Assistant Clinical Scientist, MSRCNY

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Thinking Through Tysabri

• It is a very effective medication
• Succeeded in patients where other drugs have not
• Prevents disability, relapses, and MRI changes
• Side effects are mild or uncommon
• Tysabri is not for everyone
• The severe brain infection PML is still likely a
  risk
• The exact risk of PML with monotherapy is unknown
• Tysabri has not been effective in some patients

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Review of Tysabri

• A monoclonal antibody
• This is a very precise, targeted drug therapy
• It is a designed antibody
• Antibody therapy allows for, in a warfare
  analogy, facial recognition software to target
  the bullet
• Not chemotherapy
• Monthly Administration
• In the vein over 1 hour each month
• Never combined with other immune drugs
• Only by specially trained infusion centers
  registered with the TOUCH program

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Brain Inflammation in MS

• MRI

• Microscope

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How Tysabri Works

• The brain is a gated community Nutrients and
  oxygen can enter. Other cells and drugs have
  limited access.
• Above is an illustration of a lymphocyte entering
  the brain.
• Tysabri closes the highway exits to B and T
  cells.

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Tysabri is Very EffectiveTwo-year study results

• Relapse reduction 67
• Relapse-free 72
• Disability risk reduction 42
• Reduction in new lesions 83
• Patients with no new lesions 57
• Reduction in inflamed lesions 92

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Side Effects of Tysabri

• Very well tolerated overall
• No routine blood tests
• Discontinuation rate Tysabri 6 Placebo
  4
• Fatigue Tysabri 27 Placebo 21
• Allergic reactions 4
• Anaphylaxis 1
• Malignancy risk no increased risk observed
• still an unknown
• Infections No increased risk
• Few rare infections seen in Tysabri

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PMLProgressive Multifocal Leukoencephalopathy

• A severe brain infection by a very common virus
• Seen in patients with weak immune systems
• - with AIDS or strong chemotherapy
• 3/3,000 patients in the initial trials developed
  PML
• Two had MS, one was on Tysabri for Crohns
  disease
• All 3 were on combination therapy with another
  immune drug
• No patients on Tysabri alone developed PML
• The risk may or may not be lower with Tysabri
  alone
• Tysabri was pulled from the market
• No additional cases were found
• Tysabri was re-released in July 2006

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Risk of PML

• No known drug treatment
• Restoring the immune system may help
• Estimate of 1 in 1,000 risk in 18 months
• For patients on combination therapy
• Long-term risk unknown
• Monotherapy risk unknown
• Risk is comparable to other aggressive
  interventions
• 1250 to 1400 risk of leukemia with mitoxantrone

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The TOUCH program

• Developed to monitor for future cases of PML
• Designed with the FDA
• Every patient on Tysabri is monitored
• Monthly interview prior to each infusion
• Review for signs of PML
• Monthly drug review for other immune suppressants
• If a patient were to develop PML, all physicians
  would be alerted
• This will detect PML early, not prevent it

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Safety data as of September, 2007

• Over 17,000 patients on Tysabri
• Over 10,000 patients in the US
• Over 7,500 patients for over 6 months
• Over 3,500 patients for one year
• NO CASES OF PML TO DATE
• One-year data is too limited to lower our concern
  for PML

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Our Experience

• Over 200 patients
• Relapsing remitting MS - very good
• A few patients had no response
• Secondary progressive - variable
• Primary progressive MS - unimpressive

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When to Consider Tysabri

• Lack of response to first-line drugs
• Side effects from first-line drugs
• Aggressive-onset MS
• Special cases
• Patients needing a drug with a rapid onset

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Who should probably not consider Tysabri

• Newly diagnosed with mild MS
• If you are stable on a first-line drug
• Symptoms
• Exam
• MRI
• Pregnant patients
• If you have AIDS or take immune therapy for
  another autoimmune disease

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Questions for future research

• Will it be safe and effective in the long term?
• How long should a patient try Tysabri to
  determine if it will work?
• PML screening and treatment?