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TYSABRI Risk Management Plan
Risk management plan for MS
– TOUCH Prescribing Program (TYSABRI Outreach; Unified Commitment to Health)
Status update on MS risk management plan
Changes to risk management plan with addition of CD indication
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TYSABRI Risk Management Goals Goals and activities developed in collaboration with FDA
Risk minimization
– Promote informed benefit-risk decisions
– Minimize the risk of PML
– Potentially minimize death and disability due to PML
Risk assessment
– Determine the incidence and risk factors for PML, serious opportunistic Infections
– Assess long-term safety in clinical practice
4Current TYSABRI Labeling - MSBoxed Warning
TYSABRI increases risk of PML
PML may occur with TYSABRI monotherapy
Healthcare professionals should be alert to any signs or symptoms that may be suggestive of PML
– Dosing should be suspended immediately at the first signs or symptoms suggestive of PML
– Evaluation should include brain MRI and CSF for JCV DNA
Warning against
– Use in patients who are immunocompromised
– Concurrent use with immunosuppressants or immunomodulators
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TYSABRI Risk Minimization System – MS
ControlledCentralized Distribution
RegisteredInfusion Centers
NeurologistsNeurologists
MS PatientsMS Patients
Infusion Infusion NursesNurses
Mandatory Enrollment
Form
TOUCHPrescribing
Program
6Prescriber-Patient Acknowledgement
on Enrollment Form
Records informed benefit-risk decision before start of therapy
Physician signs– Is aware of PML risk
– Has discussed risks and benefits with patient
– Patient appropriate for TYSABRI
Patient signs– Has read Medication Guide
– Has discussed risks and benefits with physician
– Will report new or worsening symptoms to their physician
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Prescriber Requirements Must report any PML, serious opportunistic infection, or death
to the Sponsor
Must complete a Patient Reauthorization Questionnaire on every patient every 6 months and submit to the Sponsor
– Vital status, PML, and other serious opportunistic infections
– Any concurrent immunomodulatory or immunosuppressant medications
– Reauthorization of TYSABRI dosing for next 6 months
Must complete Discontinuation Questionnaire within 6 months of patient’s last dose and submit to the Sponsor
Sponsor screens and follows-up with prescriber if issues seen
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Infusion Center Requirements
Infusion center must be trained prior to registration
TYSABRI use only in registered infusion centers
Dosing only to patients enrolled in TOUCH Prescribing Program
Prior to each dose for each patient – infusion nurse must
– Provide Medication Guide
– Complete Pre-infusion Patient Checklist
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Pre-Infusion Patient Checklist Administered by infusion nurse
Screen for new or worsening symptoms
Screen for use of immunomodulatory or immunosuppressive medications - reinforces use as monotherapy
If either reported - dosing withheld, physician contacted immediately
Real-time submission of Pre-Infusion Patient Checklists to Sponsor
10Risk Assessment – TOUCH Prescribing Program Patient Registry
Purpose
To determine incidence of, and risk factors for, PML and other serious opportunistic infections in patients receiving TYSABRI
Safety follow-up of all patients receiving TYSABRI
Physicians report any PML, serious opportunistic infection, or death to the Sponsor for further analysis and follow-up
Follow-up of patient deaths through National Death Index and collection of death certificates
Provides safety surveillance and tracking of all patients, far exceeding routine pharmacovigilance
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Evaluation of Risk Management Plan
Monitor success of risk management plan
Includes analysis of safety and compliance data
Share data with FDA every 3 months
If needed, rapid implementation
– Labeling changes
– New risk minimization tools
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Worldwide TYSABRI Exposure – MS ~11,500 patients on TYSABRI therapy worldwide in
commercial use between June 2006 and May 2007
– US: 11,015 patients enrolled in TOUCH
• 8313 patients dosed (median of 4 doses)
• 1750 physicians have enrolled patients
• 1750 infusion sites trained and authorized
– Europe: ~3200 patients dosed to date
1000 patients on TYSABRI in clinical trials
21,000 patients – all exposure (all clinical trials, both post-marketing periods)
14Excellent Compliance withTOUCH Program – MS
Patients and prescribers informed about risk– 99.9% of patients enrolled at time of infusion
Prescribed as monotherapy, according to label– 96.8% patients with no concurrent immunomodulatory or
immunosuppressant therapies Drug being shipped to registered infusion centers
– 99.9% of 10,126 drug shipments shipped to registered infusion centers
Facilitates clinical vigilance and use in appropriate patients– 99.9% of 38,898 Pre-infusion Patient Checklists received
• 8% of infusions delayed due to patient responses • ~0.5% of infusions not given following physician contact
Note: TYSABRI metrics as of 23 May 2007
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High Level of Awareness – MS
High awareness of PML risk
– 99% of prescribers know of increased risk of PML
Key components of TOUCH well understood
– 100% of nurses know TYSABRI should be administered only to enrolled patients
– 99% of nurses know to contact prescriber if patient reports new or worsening medical problems
– 98% of prescribers know to report PML
Note: TYSABRI metrics as of 23 May 2007
16Post-Marketing Safety Profile Consistent with Clinical Trials - MS
No new confirmed cases of PML
Two serious opportunistic infections (Herpes)
Increased rate of hypersensitivity in patients who have experienced a gap in TYSABRI therapy
– Labeling change being implemented based on data from TOUCH Prescribing Program
18TYSABRI RiskMAP Key Changes for CD
Label
– Discontinue TYSABRI therapy if no response within 3 months
– Eliminate corticosteroid use within 6 months of starting TYSABRI or stop TYSABRI therapy
Training/Communication plan
– CD-specific training of infusion sites
– Education of patients and gastroenterologists of risk, and features, of PML
Additional observational cohort study in CD
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Monitoring for PML in CD Setting CD patients generally have normal
neurological function
PML symptoms consist of
– Cognitive or behavioral changes
– Visual dysfunction
– Unilateral motor weakness
Symptoms will be readily apparent to CD patients and caregivers
– Clearly unrelated to underlying disease
– Prompt early contact for evaluation and early referral to neurologist
20Features of CD Related to Risk Management
Expect TYSABRI to be prescribed by gastroenterologists who specialize in IBD
Gastroenterologists administer immunosuppressive therapies - familiar with serious complications, including CNS demyelination
– Routinely refer to specialty physicians for further evaluation
– No expectation to serve role as PML diagnostician
CD patients show willingness to weigh treatment benefits and risks
Regular contact with healthcare professionals at monthly infusions
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Risk Minimization – CD Indication
All major features remain the same
– Mandatory registration of all prescribers and patients
– Controlled, centralized distribution
– Use only in registered infusion centers
– Real-time submission of monthly pre-infusion patient checklist
– Mandatory physician re-authorization of dosing every 6 months
TOUCH forms adapted for CD
22Risk Assessment – TYSABRI Observational Cohort Study (CD)
Purpose
Evaluation of TYSABRI long-term safety in clinical practice setting
Sub-set of patients from CD-TOUCH Patient Registry
– Voluntary observational cohort study
Collects all serious adverse events
Assess risk of serious infections and malignancies
Investigate potential signals of unanticipated adverse events
4000 CD patients followed for 5 years
Powered to detect rare events with rate of 0.2 per 1000 person-years