Exjade (deferasirox; ICL670) NDA 21-882
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Transcript Exjade (deferasirox; ICL670) NDA 21-882
DRA Introduction 8-3-05.ppt
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Exjade® (deferasirox; ICL670)
NDA 21-882
United States Food and Drug Administration
Blood Products Advisory Committee Meeting
September 29, 2005
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Exjade® (deferasirox; ICL670)
NDA 21-882
Introduction
PK Narang, PhD, FCP
Vice President, Global Head
Drug Regulatory Affairs—Oncology
Novartis Pharmaceuticals Corporation
DRA Introduction 8-3-05.ppt
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
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DRA Introduction 8-3-05.ppt
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Iron Overload
Overview
Transfusional iron overload
– Serious complication in patients with transfusiondependent 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
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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
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ICL670
Proposed Indication
ICL670 is indicated for the treatment of chronic
iron overload due to blood transfusions
(transfusional hemosiderosis) in adult and
pediatric patients (≥ 2 years old)
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DRA Introduction 8-3-05.ppt
ICL670
Regulatory 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
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ICL670
Development Program Basis
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
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Key ICL670 Efficacy and Safety Trials
β-thalassemia and Other Rare Anemias
Trial/Design
0107
Phase 3
Randomized, open label,
comparator-controlled
N
586
0108
Phase 2
Open label,
noncomparative
184
0109
Phase 2
Randomized, open label,
comparator-controlled
195
Treatments
(duration)
ICL670
5, 10, 20, 30 mg/kg
vs
DFO 20 - 60 mg/kg
(1 year)
ICL670
5, 10, 20, 30 mg/kg
(1 year)
ICL670
5, 10, 20, 30 mg/kg
vs
DFO 20 - 60 mg/kg
(1 year)
Safety: Included study 106 (40 pediatric thalassemia patients).
DFO = Desferal® (deferoxamine).
Patient population
β-thalassemia
Pediatric: (≥ 2 years
old) and adult
β-thalassemia/rare
anemias
Pediatric: (≥ 2 years
old) and adult
Sickle cell disease
Pediatric: (≥ 2 years
old) and adult
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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