Asthma and COPD Drug Discoveries: What the future holds World Leaders in Health Industry Analysis
Asthma and COPD Drug Discoveries: what the future holds ISBN: 1 85822 264 8 Copyright 2006 Espicom Business Intelligence All rights reserved. No part of this publication may be reproduced or used in any form or by any means graphic, electronic or mechanical, including photocopying, recording, taping or storage in information retrieval systems without the express permission of the publisher. Every care has been taken to ensure that the information contained in this report is correct. The publisher accepts no liability for decisions made on the basis of information contained herein. British Library Cataloguing in Publication Data. A catalogue record for this report is available from the British Library.
Asthma and COPD Drug Discoveries: what the future holds Published by Espicom Business Intelligence, August 2006 www.espicom.com
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Contents Foreword... 1 Executive Summary... 3 What are Asthma and COPD?... 5 Morbidity and Mortality...5 Diagnosis and Treatment... 7 Asthma Management...8 COPD Management...9 Pharmacotherapy... 10 Current Market Leaders... 12 Drugs in the Pipeline... 14 Competitor Ratio Analysis... 18 Short-Acting Beta-2 Agonists... 19 Xopenex (levalbuterol)... 19 Sales Forecast...20 Patent Challenges...21 Clinical Trials...21 Xopenex versus racemic albuterol in COPD...21 Xopenex HFA study...21 Xopenex in the emergency room...22 Inhaled Corticosteroids... 23 Flixotide/Flovent (fluticasone propionate)... 23 Sales Forecasts...24 Clinical Trials...25 Pulmicort (budesonide)... 27 Sales Forecast...28 Patent Challenge...29 Clinical Trials...29 START budesonide during pregnancy...29 START budesonide in children with mild persistent asthma...30 START safety outcome data...30 EUROSCOP...31 Long-term data from early intervention study in Finland...31 Asmanex (mometasone furoate)... 33 Sales Forecasts and Assumptions...34 Competitor Ratio Analysis...34 Novelty/rationale for mechanism of action...34 Proof of concept/clinical data...35 August 2006 i
Management/clinical expertise... 35 Competition within marketplace... 35 Risks associated with drug development in therapeutic class... 35 Clinical Trials... 35 Patients previously maintained on bronchodilators alone... 35 Patients previously maintained on inhaled corticosteroids... 36 Patients previously maintained on oral corticosteroids... 37 Alvesco (ciclesonide)... 38 Sales Forecast and Assumptions... 39 Competitor Ratio Analysis... 39 Novelty/rationale for mechanism of action... 39 Proof of concept/clinical data... 40 Management/clinical expertise... 40 Competition within marketplace... 40 Risks associated with drug development in therapeutic class... 40 Clinical trials... 40 Ciclesonide versus fluticasone propionate... 40 Low incidence of oropharyngeal side effects... 41 Ciclesonide versus budesonide and fluticasone... 41 Intranasal formulation... 42 Ciclesonide versus budesonide... 42 Muscarinic Antagonists... 44 Spiriva (tiotropium)... 44 Sales Forecast and Assumptions... 45 Competitor Ratio Analysis... 45 Novelty/rationale for mechanism of action... 45 Proof of concept/clinical data... 45 Management/clinical expertise... 46 Competition within marketplace... 46 Risks associated with drug development in therapeutic class... 46 Clinical Trials... 46 Pooled Studies... 46 Study on COPD patients in France... 47 Spiriva+formoterol versus salmeterol+fluticasone propionate... 47 UPLIFT... 48 TIPHON... 48 Combination Therapy... 50 Seretide/Advair (salmeterol+fluticasone propionate)... 50 Sales Forecasts... 51 Patent Challenge... 52 ii August 2006
Safety Issues...52 Clinical Trials: COPD...53 TORCH...53 TRISTAN...53 Clinical Trials: Asthma...55 Biopsy Study in Moderate Asthma...55 EXCEL...55 GOAL...56 Advair versus montelukast...56 Symbicort (budesonide+formoterol)... 58 Sales Forecast...59 European patent challenge...60 Clinical Trials: COPD...60 Calverly et al....61 Clinical Trials: Asthma...61 SUND...61 STAY...62 Head to head study: Symbicort Turbuhaler versus Seretide (salmeterol+fluticasone)...62 Clinical Trials: Asthma+COPD...63 ASSURE...63 Leukotriene Receptor Antagonists... 64 Singulair (montelukast)... 64 Sales Forecast...65 Clinical Trials...66 PREVIA...66 Anti-Immunoglobulin E Therapy... 67 Xolair (omalizumab)... 67 Sales Forecast and Assumptions...68 Competitor Ratio Analysis...69 Novelty/rationale for mechanism of action...69 Proof of concept/clinical data...69 Management/clinical expertise...69 Competition within marketplace...70 Risks associated with drug development in therapeutic class...70 Clinical Trials...70 Long-term data...70 Pooled study data...71 Drugs in Development... 73 PDE-IV Inhibitors... 73 Ariflo (cilomilast)... 73 August 2006 iii
Sales Forecasts and Assumptions... 74 Competitor Ratio Analysis... 74 Novelty/rationale for mechanism of action... 74 Proof of concept/clinical data... 75 Management/clinical expertise... 75 Competition within marketplace... 75 Risks associated with drug development in therapeutic class... 75 Clinical trials... 75 Daxas (roflumilast)... 77 Sales Forecasts and Assumptions... 77 Competitor Ratio Analysis... 78 Novelty/rationale for mechanism of action... 78 Proof of concept/clinical data... 78 Management/clinical expertise... 79 Competition within marketplace... 79 Risks associated with drug development in therapeutic class... 79 Clinical Trials... 79 Efficacy & safety study in COPD... 79 RATIO/M2-112... 80 RECORD... 80 Other studies... 81 Long-Acting Beta Agonists... 82 Arformoterol... 82 Sales Forecasts and Assumptions... 82 Competitor Ratio Analysis... 83 Novelty/rationale for mechanism of action... 83 Proof of concept/clinical data... 83 Management/clinical expertise... 83 Competition within marketplace... 84 Risks associated with drug development in therapeutic class... 84 Clinical Trials... 84 Indacaterol... 86 Sales Forecast and Assumptions... 86 Competitor Ratio Analysis... 87 Novelty/rationale for mechanism of action... 87 Proof of concept/clinical data... 87 Management/clinical expertise... 87 Competition within marketplace... 87 Risks associated with drug development in therapeutic class... 88 Clinical Trials... 88 iv August 2006
GSK 159797... 89 Sales Forecasts and Assumptions...89 Competitor Ratio Analysis...90 Novelty/rationale for mechanism of action...90 Proof of concept/clinical data...90 Management/clinical expertise...90 Competition within marketplace...91 Risks associated with drug development in therapeutic class...91 Clinical Trials...91 Long-Acting Muscarinic Antagonists... 92 NVA237... 92 Sales Forecast and Assumptions...92 Competitor Ratio Analysis...93 Novelty/rationale for mechanism of action...93 Proof of concept/clinical data...93 Management/clinical expertise...93 Competition within marketplace...94 Risks associated with drug development in therapeutic class...94 Clinical Trials...94 SOURCES... 95 Espicom Sources... 95 Others... 95 August 2006 v
List of Tables Deaths from COPD and Asthma in Major Markets, 2002...6 Deaths from COPD and Asthma in the USA, 2002...6 GINA Stepwise Approach to Asthma Medication...8 GOLD Therapy Recommendations for COPD... 10 Leading Asthma and COPD Therapies by Sales Value, 2004-2005 (US$ Million)... 12 US Patent Expiry for Major Asthma and COPD Therapies... 13 Launched Products in Development... 14 Novel Drugs in Development... 16 Competitor Ratio Analysis Summary... 18 Xopenex Sales, 2001-2005 (US$ Million)... 19 Flixotide/Flovent Sales, 2001-2005 ( & US$ Million)... 23 Pulmicort Sales, 2001-2005 (US$ Million)... 27 Spiriva Sales, 2002-2005 (Euros & US$ Million)... 44 Advair/Seretide Sales, 2001-2005 ( & US$ Million)... 50 Symbicort Sales, 2001-2005 (US$ Million)... 58 Singulair Sales, 2002-2005 (US$ Million)... 64 Xolair Sales, 2003-2005 (US$ Million)... 67 Xolair Projected Sales, 2005-2011 (US$ Million)... 69 List of Figures Novel Drugs in Clinical Development by Activity... 17 Xopenex Projected Sales, 2005-2011 (US$ Million)... 20 Flixotide/Flovent Projected Sales, 2005-2011 (US$ Million)... 25 Pulmicort Projected Sales, 2005-2011 (US$ Million)... 29 Asmanex Twisthaler Projected Sales, 2005-2011 (US$ Million)... 34 Alvesco Projected Sales, 2005-2012 (US$ Million)... 39 Spiriva Projected Sales, 2005-2011 (US$ Million)... 45 Seretide/Advair Projected Sales, 2005-2011 (US$ Million)... 52 Symbicort Projected Sales, 2005-2011 (US$ Million)... 60 Singulair Projected Sales, 2005-2011 (US$ Million)... 66 Ariflo Projected Sales, 2007-2012 (US$ Million)... 74 Daxas Projected Sales, 2008-2013 (US$ Million)... 78 Arformoterol Projected Sales, 2007-2012 (US$ Million)... 83 vi August 2006
Indacaterol Projected Sales, 2009-2014 (US$ Million)... 87 GSK 159797 Projected Sales, 2008-2013 (US$ Million)... 90 NVA237 Projected Sales, 2009-2014 (US$ Million)... 93 August 2006 vii