1. Exjade® (deferasirox; ICL670) NDA 21-882
Core Introduction (CI)
4/26/2017 4:34 PM
DRA Introduction ppt
Exjade® (deferasirox; ICL670) NDA
United States Food and Drug Administration Blood Products Advisory Committee Meeting
September 29, 2005

2. Exjade® (deferasirox; ICL670) NDA 21-882 Introduction
Core Introduction (CI)
4/26/2017 4:34 PM
DRA Introduction ppt
Exjade® (deferasirox; ICL670) NDA Introduction
PK Narang, PhD, FCP Vice President, Global Head Drug Regulatory Affairs—Oncology Novartis Pharmaceuticals Corporation

3. Core Introduction (CI)
DRA Introduction ppt
4/26/2017 4:34 PM
ICL670 Sponsor’s Agenda
Introduction
PK Narang, PhD, FCP Vice President, Drug Regulatory Affairs—Oncology Novartis Pharmaceuticals Corporation
Iron Overload: Complications and Need for Therapy
John B. Porter, MD Professor of Haematology University College, London, UK
Efficacy and Safety
Peter Marks, MD, PhD Senior Director, Oncology Clinical Development Novartis Pharmaceuticals Corporation
Benefit/Risk
Elliott Vichinsky, MD Director, Hematology/Oncology Children’s Hospital and Research Center at Oakland Oakland, California

4. Iron Overload Overview
Core Introduction (CI)
4/26/2017 4:34 PM
Iron Overload Overview
DRA Introduction ppt
Transfusional iron overload
Serious complication in patients with transfusion- dependent anemias
Significant morbidity/mortality for inadequately chelated patients
Current “gold standard” therapy—Desferal® (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. Core Introduction (CI)
4/26/2017 4:34 PM
ICL670 Overview
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

6. ICL670 Proposed Indication
Core Introduction (CI)
4/26/2017 4:34 PM
ICL670 Proposed Indication
DRA Introduction 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. ICL670 Regulatory History
Core Introduction (CI)
4/26/2017 4:34 PM
ICL670 Regulatory History
IND submitted
Orphan designation
Fast-track status
SPA for 0107, 0108,
NDA accepted in CMA-1 program Jan 2005
NDA submission completed May 2005
Priority review granted Jun 2005
DRA Introduction ppt

8. ICL670 Development Program Basis
Core Introduction (CI)
4/26/2017 4:34 PM
ICL670 Development Program Basis
DRA Introduction ppt
β-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

9. Core Introduction (CI)
4/26/2017 4:34 PM
Key ICL670 Efficacy and Safety Trials β-thalassemia and Other Rare Anemias
DRA Introduction ppt
Trial/Design N
Treatments (duration)
Patient population
0107
Phase 3
Randomized, open label, comparator-controlled
586
ICL670 5, 10, 20, 30 mg/kg vs
DFO mg/kg (1 year)
β-thalassemia
Pediatric: (≥ 2 years old) and adult
0108
Phase 2
Open label, noncomparative
184
ICL670 5, 10, 20, 30 mg/kg (1 year)
β-thalassemia/rare anemias
0109
195
Sickle cell disease
Safety: Included study 106 (40 pediatric thalassemia patients).
DFO = Desferal® (deferoxamine).

10. ICL670 Questions & Answers
Core Introduction (CI)
DRA Introduction ppt
4/26/2017 4:34 PM
ICL670 Questions & Answers
Consultants
John Porter, MD Professor of Haematology University College, London
Elliott Vichinsky, MD Director, Hematology/Oncology Children’s Hospital and Research Center at Oakland
Alan Cohen, MD Physician-in-Chief and Medical Director, Thalassemia Program Children’s 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