1 Risk Management Considerations for Romiplostim Suzanne Berkman, PharmD Senior Risk Management Analyst Division of Risk Management Office of Surveillance and Epidemiology

2 What is Risk Management? Risk assessment + Risk minimization Risk assessment + Risk minimization Routine risk management Routine risk management Labeling Labeling Spontaneous adverse event monitoring Spontaneous adverse event monitoring Additional measures Additional measures Education and communication plans Education and communication plans Distribution linked to safe use Distribution linked to safe use Risk assessment studies Risk assessment studies

3 Amgen’s Proposal Risk minimization Risk minimization Education and communication plan Education and communication plan Medication Guide, training kit, pre-use checklist Medication Guide, training kit, pre-use checklist Controlled distribution Controlled distribution Risk assessment Risk assessment Evaluation of program data Evaluation of program data Further studies Further studies No direct-to-consumer advertising No direct-to-consumer advertising

4 Further Considerations for Romiplostim

5 Possible Criteria for Appropriate Patient Selection Should the duration of ITP be specified? Should the duration of ITP be specified? Limit to splenectomized patients? Limit to splenectomized patients? How should ‘insufficient response,’ and ‘intolerance’ be defined? How should ‘insufficient response,’ and ‘intolerance’ be defined? Should a particular platelet count be specified? Should a particular platelet count be specified? Should a bone marrow biopsy be required? Should a bone marrow biopsy be required? Should patients with a known history of bone marrow stem cell disorder be considered? Should patients with a known history of bone marrow stem cell disorder be considered? Should patients with active malignancy be considered? Should patients with active malignancy be considered? Should certain concomitant medication use be discouraged? Should certain concomitant medication use be discouraged? Other considerations? Other considerations?

6 Patient Monitoring What to monitor? What to monitor? How often to monitor? How often to monitor? How to collect the data? How to collect the data?

7 Risk Management Example: Tysabri ® (natalizumab)

8 Tysabri ® (natalizumab) Indications Indications Multiple Sclerosis (MS) Multiple Sclerosis (MS) Crohn’s disease Crohn’s disease Risk Risk Progressive Multifocal Leukoencephalopathy (PML) Progressive Multifocal Leukoencephalopathy (PML) Risk Management Program Risk Management Program Tysabri Outreach Unified Commitment to Health (TOUCH) Prescribing Program Tysabri Outreach Unified Commitment to Health (TOUCH) Prescribing Program

9 TOUCH Prescribing Program Goals Goals Minimize the risk and health consequences of PML Minimize the risk and health consequences of PML Promote informed risk-benefit decisions Promote informed risk-benefit decisions Further assess the safety profile of natalizumab Further assess the safety profile of natalizumab Reinforces Reinforces Appropriate patient selection Appropriate patient selection Risk communication Risk communication Close patient monitoring and data collection Close patient monitoring and data collection

Prescriber/ Patient Infusion Site TOUCH Prescribing Program Prescriber/ patient complete Enrollment Form Assigns patient to authorized infusion site Changes patient status to ‘authorized’ in TOUCH online or provides Notice of Patient Authorization Infusion Site confirms patient is authorized to receive natalizumab Patient receives natalizumab infusion based on answer to Pre-Infusion Checklist Pre-Infusion Patient Checklist is submitted via TOUCH online or faxed by Infusion Site 6-month authorization periods begins and Pre- Infusion Patient Checklists are tracked monthly Tracks all patients every 6 months Prescriber completes Reauthorization Form every 6 months

11 Differences to Consider Romiplostim Weekly subcutaneous injection Weekly subcutaneous injection Administered in prescriber’s office Administered in prescriber’s office Specific laboratory monitoring? Specific laboratory monitoring? Multiple serious risks Multiple serious risks Preventable, manageable? Preventable, manageable? Long term safety is a concern Long term safety is a concern Off-label use within prescriber’s expertise Off-label use within prescriber’s expertise Tysabri ® (natalizumab) Monthly infusion Administered in infusion center No specific laboratory monitoring One serious known risk Preventable, manageable? Long term safety is a concern Off-label use outside of neurology

12 Summary Mandatory enrollment of prescribers, patients, other healthcare providers, and distributors Mandatory enrollment of prescribers, patients, other healthcare providers, and distributors Clear criteria to identify the target patient population Clear criteria to identify the target patient population Mandatory education Mandatory education Mandatory regular monitoring Mandatory regular monitoring Long-term data collection on all treated patients Long-term data collection on all treated patients

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