Peripheral & Central Nervous System Drugs Advisory Committee January 28, 2000

2/15/00


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Table of Contents

Peripheral & Central Nervous System Drugs Advisory Committee January 28, 2000

Mitoxantrone Approved Indications

Mitoxantrone Use in Cancer Patients

Mitoxantrone Mechanism of Action

Proposed Mechanism of Action in MS

Multiple Sclerosis

Mitoxantrone for MS - Regulatory History

Requested Approval

Presentation Agenda

Study Investigators

Immunex Advisors

Mitoxantrone in Multiple Sclerosis (MS)

Mitoxantrone in Multiple Sclerosis Data Presentation and Discussion

Published Studies of Mitoxantrone in MS

Studies in Mitoxantrone Filing in MS

Study 901 Design and Efficacy Results

Study 901 - MIMS Trial

Study 901 - Inclusion Criteria

Kurtzke EDSS Scoring System

Study 901 - Exclusion Criteria

Study 901 - Design

Study 901 - Masking Study Drug

Study 901 - Primary Efficacy Criterion

Study 901 - Test of Individual Efficacy Variables

Study 901 - Kurtzke Expanded Disability Status Scale (EDSS)

Study 901 - AI and SNS Scales

Study 901 - Disposition of Patients

Study 901 - Early Drug Discontinuation

Study 901 - Baseline Demographics

Study 901 - Baseline Demographics Disease Status

Study 901 - Primary Efficacy Criterion

Study 901 - Mean Change in EDSS

Study 901 - Mean Change in AI

Study 901 - Mean Change in SNS Score

Study 901 - Total Number Treated Relapses (Adjusted for Dropouts)

Study 901 - Time to First Treated Relapse

Study 901 - Secondary Efficacy Variables

Study 901 - Mean Change in EDSS Quarterly Months 3 to 24

Study 901 - EDSS ? 1.0 Point Deterioration Sustained for 6 Months

Study 901 - Categorized ? 1.0 Point EDSS Change

Study 901 - Patients Without Relapses

Study 901 - Annualized Relapse Rate

Study 901 - Neurologic Disability Assessment at Month 36*

Study 901 - Relapse Rate Months 24 to 36*

Study 901 - Time to First Treated Relapse - Month 0 to 36*

Study 901 - Clinical Efficacy Conclusions

Study 901 - MRI Subgroup Evaluation

Study 901 - Patients with Gd-Enhancing Lesions

Study 901 - Patients with New Gd-Enhancing Lesions

Study 901 - Change in Total T2-Weighted Lesion Load (Score 1 - 5)

Study 901 - MRI Efficacy Conclusions

Study 902 Design and Efficacy Results

Study 902 - Phase II Trial in Active MS

Study 902 - Inclusion Criteria

Study 902 - Exclusion Criteria

Study 902 - Design

Study 902 - Efficacy Evaluations

Study 902 - Study Endpoints

Study 902 - Patient Disposition

Study 902 - Baseline Demographics

Study 902 - Patients With New Gd-Enhancing Lesions

Study 902 - Mean (±SEM) Number of New Gd-Enhancing Lesions

Study 902 - Mean (±SEM) EDSS Change

Study 902 - Categorized ? 1.0 Point EDSS Change

Study 902 - Relapse Assessment

Study 902 - Efficacy Conclusions

Mitoxantrone Safety Data

Mitoxantrone Safety Experience

Study 901 - Discontinuation Due to AE

Study 901 - Clinical Adverse Events More Frequent (p?0.05) in Either Mitoxantrone Group

Study 901 - Clinical Adverse Events in ? 10% of Patients

Study 901 - Cardiac Monitoring

Study 901 - Number of Patients with LVEF ? 50%

Study 901 - LVEF Values ? 50% Month 24 to 36

Study 901 - Additional Safety Information

Study 901 - Hematology Results ? Normal*

Study 901 - Serum Chemistries ? Normal*

Study 902 - Adverse Events

Study 902 - Grade 3-4 Hematologic Toxicity of Mito + mP*

Study 903 - Long Term Safety Database

Study 903 - Data Collection and Quality Assurance

Study 903 - Treatment Guidelines

Study 903 - Baseline Demographics

Study 903 - Mitoxantrone Dosing (N=454)

Study 903 - Mortality (N=454)

Study 903 - Pregnancies

Study 903 - Cardiac Abnormalities

Mitoxantrone Cardiac Effects in Cancer Patients*

Mitoxantrone Safety Conclusions

Risk & Benefit Assessment

Acute Adverse Events

Laboratory Monitoring

Cardiac Monitoring

Pregnancy

Benefit of Mitoxantrone - Study 901

Benefit of Mitoxantrone - Supportive Studies

Discussion

Adequacy of Controlled Study 901

Adequacy of Controlled Study 902

Mitoxantrone Slows Progression of Neurologic Disability - Study 901

Mitoxantrone Slows Progression of Neurologic Disability - Study 902

Mitoxantrone Decreases Relapse

MRI Results - Study 901

MRI Results - Study 902

Dose - 12 mg/m2 Every 3 Months

Target Population

Mitoxantrone in Multiple Sclerosis: A Clinician’s Perspective

Clinical Courses of MS

Mechanisms of Worsening of MS

Mechanisms of Worsening of MS

PPT Slide

Clinical Courses of MS - Worsening Forms of Relapsing or Progressive Disease

Conclusions

Effectiveness of Mitoxantrone in MS

Proposed Use of Mitoxantrone in MS

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