# Presentation: 785143

## Exjade® (deferasirox; ICL670)NDA 21-882

**DRA Introduction 8-3-05.ppt**

**United States Food and Drug Administration****Blood Products Advisory Committee Meeting**
**September 29, 2005**

## 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**

**DRA Introduction 8-3-05.ppt**

## Iron OverloadOverview

**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**

**DRA Introduction 8-3-05.ppt**

## 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**

## 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)**

**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****	****	****	****	**

**DRA Introduction 8-3-05.ppt**

## 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**

**DRA Introduction 8-3-05.ppt**

## Key ICL670 Efficacy and Safety Trialsβ-thalassemia and Other Rare Anemias

| 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 20 - 60 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
Pediatric: (≥ 2 years old) and adult |
| 0109
Phase 2
Randomized, open label,comparator-controlled | 195 | ICL6705, 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).**

**DRA Introduction 8-3-05.ppt**

## 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**

**DRA Introduction 8-3-05.ppt**