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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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
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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