Exjade

1
Exjade (deferasirox ICL670)NDA 21-882
DRA Introduction 8-3-05.ppt

• United States Food and Drug AdministrationBlood
  Products Advisory Committee Meeting
• September 29, 2005

2
Exjade (deferasirox ICL670)NDA
21-882Introduction
DRA Introduction 8-3-05.ppt

• PK Narang, PhD, FCPVice President, Global
  HeadDrug Regulatory AffairsOncologyNovartis
  Pharmaceuticals Corporation

3
ICL670Sponsors Agenda
DRA Introduction 8-3-05.ppt

• Introduction
• PK Narang, PhD, FCPVice President, Drug
  Regulatory AffairsOncologyNovartis
  Pharmaceuticals Corporation
• Iron Overload Complications and Need for Therapy
• John B. Porter, MDProfessor of
  HaematologyUniversity College, London, UK
• Efficacy and Safety
• Peter Marks, MD, PhDSenior Director, Oncology
  Clinical DevelopmentNovartis Pharmaceuticals
  Corporation
• Benefit/Risk
• Elliott Vichinsky, MDDirector,
  Hematology/OncologyChildrens Hospital and
  Research Center at OaklandOakland, California

4
Iron OverloadOverview
DRA Introduction 8-3-05.ppt

• Transfusional iron overload
• Serious complication in patients with
  transfusion- dependent anemias
• Significant morbidity/mortality for inadequately
  chelated patients
• Current gold standard therapyDesferal
  (Novartis)
• Only approved/available iron chelator in US
• Safe and effective (but parenteral)
• Poor compliance a significant issue
• Unmet medical need
• Safe, effective agent with positive benefit/risk

5
ICL670Overview

• A new class of tridentate iron chelator
• Orally dosed
• Drug kinetics support once-a-day dosing
• Efficacy similar to Desferal
• Acceptable safety in adults and children

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ICL670Proposed Indication
DRA Introduction 8-3-05.ppt

• ICL670 is indicated for the treatment of chronic
  iron overload due to blood transfusions
  (transfusional hemosiderosis) in adult and
  pediatric patients ( 2 years old)

7
ICL670Regulatory History

• IND submitted 1999
• Orphan designation 2002
• Fast-track status 2003
• SPA for 0107, 0108, 0109 2003
• NDA accepted in CMA-1 program Jan 2005
• NDA submission completed May 2005
• Priority review granted Jun 2005

DRA Introduction 8-3-05.ppt
8
ICL670Development Program Basis
DRA Introduction 8-3-05.ppt

• ß-thalassemia as a model for documenting
  effectiveness
• Largest prospective trials for an iron chelator
• Efficacy may be applicable to other conditions of
  transfusional iron overload including sickle cell
  disease
• Document safety in sickle cell disease and other
  rare anemias
• Provide sufficient pediatric data in pivotal
  trials
• 45 of patients

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Key ICL670 Efficacy and Safety Trialsß-thalassemi
a and Other Rare Anemias
DRA Introduction 8-3-05.ppt
Trial/Design N Treatments(duration) Patient population
0107 Phase 3 Randomized, open label,comparator-controlled 586 ICL6705, 10, 20, 30 mg/kg vs DFO 20 - 60 mg/kg(1 year) ß-thalassemia Pediatric ( 2 years old) and adult
0108 Phase 2 Open label,noncomparative 184 ICL6705, 10, 20, 30 mg/kg(1 year) ß-thalassemia/rare anemias Pediatric ( 2 years old) and adult
0109 Phase 2 Randomized, open label,comparator-controlled 195 ICL6705, 10, 20, 30 mg/kg vs DFO 20 - 60 mg/kg(1 year) Sickle cell disease Pediatric ( 2 years old) and adult
Safety Included study 106 (40 pediatric
thalassemia patients). DFO Desferal
(deferoxamine).
10
ICL670Questions Answers
DRA Introduction 8-3-05.ppt

• Consultants
• John Porter, MD Professor of Haematology
  University College, London
• Elliott Vichinsky, MD Director,
  Hematology/Oncology Childrens Hospital
  and Research Center at Oakland
• Alan Cohen, MD Physician-in-Chief and Medical
  Director, Thalassemia Program Childrens
  Hospital of Philadelphia
• Richard Larson, MD Professor of
  Medicine University of Chicago
• Raimund Hirschberg, MD Professor of
  Medicine Harbor-UCLA Medical Center
• Lloyd Fisher, PhD Professor Emeritus Department
  of Biostatistics University of Washington