Contents:

ASTHMA: OPINION LEADER FORUM EXPERT’S VIEWS AND PERSPECTIVE ON DIAGNOSIS, TREATMENT, PRODUCT PERFORMANCE…AND CLOSING THE NEED GAP EXECUTIVE SUMMARY.........................................................................................................................................I SECTION 1 INTRODUCTION................................................................................................................................ 1 1.1 SCOPE AND OBJECTIVES OF RESEARCH INVESTIGATION........................................................... 1 1.2 METHODOLOGY OF INVESTIGATION................................................................................................ 2 1.3 LIMITATIONS OF INVESTIGATION ..................................................................................................... 4 SECTION 2 GENERAL ISSUES IN THE MANAGEMENT OF ASTHMA........................................................ 5 2.1 FUNDAMENTALS OF THE CONDITION .............................................................................................. 5 2.2 INCIDENCE AND PREVALENCE OF ASTHMA................................................................................... 6 2.3 ETIOLOGY AND PATHOPHYSIOLOGY OF ASTHMA ....................................................................... 9 2.4 SCREENING, DIAGNOSIS, AND CLASSIFICATION OF ASTHMA ................................................. 15 2.5 IMPACT AND CHALLENGES OF ASTHMA....................................................................................... 20 SECTION 3 CLINICAL MANAGEMENT OF ASTHMA................................................................................... 31 3.1 PHARMACEUTICAL STRATEGIES FOR MANAGING THE CONDITION...................................... 31 3.2 PATIENT CARE STRATEGIES.............................................................................................................. 48 SECTION 4 ISSUES IN CURRENT PHARMACEUTICAL APPROACHES TO THE MANAGEMENT OF ASTHMA ..................................................................................................................................... 73 SECTION 5 PRODUCT DEVELOPMENT FOR THE MANAGEMENT OF ASTHMA................................ 81 5.1 COMMENTARY BY RESPONDENTS TO THIS REPORT.................................................................. 88 SECTION 6 THE ASTHMA MARKET: DELIVERY SYSTEM ISSUES........................................................ 107 SECTION 7 NEEDS/GAPS ANALYSIS OF THE MANAGEMENT OF ASTHMA....................................... 135 7.1 NEEDS/GAPS IN THE CURRENT MANAGEMENT OF ASTHMA.................................................. 135 7.2 ASPECTS OF THE CURRENT MANAGEMENT OF ASTHMA NOT CONSIDERED SUBSTANTIALLY PROBLEMATICAL.............................................................................................. 141 ADDENDUM A NATIONAL ASTHMA EDUCATION AND PREVENTION PROGRAM (NAEPP/NIH): GUIDELINES FOR THE DIAGNOSIS AND MANAGEMENT OF ASTHMA ................. 147 ADDENDUM B CAUSES AND COURSE OF ASTHMA .................................................................................. 179 B.1 ETIOLOGY OF THE DISEASE ............................................................................................................ 179 B.2 PATHOPHYSIOLOGY OF THE DISEASE.......................................................................................... 186 ADDENDUM C AUDIT OF SELECTED PHARMACEUTICAL MANUFACTURERS THAT ARE STAKEHOLDERS IN ASTHMA AND OTHER RESPIRATORY INDICATIONS .......... 205 C.1 ABBOTT LABORATORIES ................................................................................................................. 205 C.2 AMERICAN HOME PRODUCTS......................................................................................................... 207 C.3 ASTRAZENECA................................................................................................................................... 209 C.4 AVENTIS............................................................................................................................................... 209 C.5 BAYER.................................................................................................................................................. 211 C.6 BOEHRINGER INGELHEIM................................................................................................................ 213 C.7 BRISTOL-MYERS SQUIBB ................................................................................................................. 213 C.8 GENENTECH........................................................................................................................................ 214 C.9 GLAXOSMITHKLINE .......................................................................................................................... 215 C.10 MERCK ................................................................................................................................................. 216 C.11 NOVARTIS ........................................................................................................................................... 218 C.12 PFIZER .................................................................................................................................................. 218 C.13 SCHERING-PLOUGH ........................................................................................................................... 220 ADDENDUM D AUDIT OF SELECTED BIOTECHNOLOGY DEVELOPMENT FIRMS THAT ARE STAKEHOLDERS IN ASTHMA AND OTHER RESPIRATORY INDICATIONS .......... 223 D.1 AMRAD................................................................................................................................................. 223 D.2 AXYS..................................................................................................................................................... 224 D.3 BYK GULDEN...................................................................................................................................... 224 D.4 CAMR.................................................................................................................................................... 225 D.5 CLARION.............................................................................................................................................. 225 D.6 DISCOVERY LABORATORIES........................................................................................................... 225 D.7 DURA PHARMACEUTICALS ............................................................................................................. 226 D.8 DYNAVAX ........................................................................................................................................... 226 D.9 HOKURIKU SEIYAKU........................................................................................................................ 227 D.10 INSPIRAPLEX...................................................................................................................................... 227 D.11 MEDIMMUNE...................................................................................................................................... 228 D.12 MILLENNIUM...................................................................................................................................... 229 D.13 NATIONAL INSTITUTES OF HEALTH.............................................................................................. 230 D.14 PROTEIN DESIGN LABS..................................................................................................................... 230 D.15 RIGEL.................................................................................................................................................... 231 D.16 UCB GROUP......................................................................................................................................... 232 ADDENDUM E HISTORICAL SALES AND MARKET ANALYSIS OF PHARMACEUTICAL PRODUCTS FOR ASTHMA.................................................................................................... 235 ADDENDUM F TECHNOLOGIES AND COMPOUNDS IN DEVELOPMENT FOR THE THERAPEUTIC MANAGEMENT OF ASTHMA............................................................................................... 241 F.1 REVIEW OF ASTHMA PRODUCT TECHNOLOGY.......................................................................... 241 F.1.1 Beta-Adrenergic Agents ............................................................................................................... 241 F.1.2 Corticosteroids............................................................................................................................. 241 F.1.3 Leukotriene Antagonists............................................................................................................... 242 F.1.4 The 5-Lipoxygenase Inhibitors..................................................................................................... 242 F.1.5 Anti-IgE....................................................................................................................................... 242 F.1.6 Cytokine Modulators.................................................................................................................... 242 F.1.7 Cell Adhesion Molecules ............................................................................................................. 243 F.1.8 T-Cell Modulators ........................................................................................................................ 243 F.1.9 Signal Transduction..................................................................................................................... 244 F.1.10 Protease Inhibitors....................................................................................................................... 244 F.1.11 Phosphodiesterase Inhibitors (Including Theophylline) ............................................................... 244 F.1.12 Histamine Receptor Regulators/Release Inhibitors ...................................................................... 244 F.1.13 Muscarinic Receptor Antagonists................................................................................................. 245 F.1.14 Ion Channel Modulators ............................................................................................................... 245 F.1.15 Phospholipase Inhibitors .............................................................................................................. 245 F.1.16 Vaccines ...................................................................................................................................... 245 F.1.17 Tachykinins ................................................................................................................................. 245 F.1.18 Platelet-Activating Factor (PAF) Antagonists.............................................................................. 246 F.1.19 Pharmacogenomics...................................................................................................................... 246 F.2 ASTHMA DRUG-DEVELOPMENT PIPELINE DIRECTIONS.......................................................... 246 F.3 THE DRUG DEVELOPMENT PIPELINE............................................................................................ 250 ADDENDUM G SELECTED RECENT EVENTS IN THE MANAGEMENT OF ASTHMA ....................... 265 G.1 SEPRACOR’S XOPENEX AND (R,R)-FORMOTEROL ..................................................................... 265 G.2 ENTELOS’S ASTHMA PHYSIOLAB .................................................................................................. 266 G.3 AMERICAN COLLEGE OF ALLERGY, ASTHMA AND IMMUNOLOGY LAUNCHED 2001 NATIONWIDE ASTHMA SCREENING PROGRAM......................................................................... 269 G.4 RIGEL-PFIZER ASTHMA/ALLERGY DRUG DISCOVERY COLLABORATION .......................... 269 G.5 MEDSCAPE DIGITAL HEALTH AGREEMENT WITH GLAXO...................................................... 270 G.6 VITAMIN E MAY LOWER RISK OF ALLERGIES, ASTHMA......................................................... 271 G.7 RESEARCHERS OBTAIN MORE EVIDENCE FOR NEW MODEL OF ASTHMA.......................... 271 G.8 MEDSTAT GROUP STUDY: COST IMPLICATIONS FOR THE USE OF INHALED ANTIINFLAMMATORY MEDICATIONS IN THE TREATMENT OF ASTHMA..................................... 273 G.9 NOVARTIS‘S AND GENENTECH’S XOLAIR: IGE AND ITS ROLE IN ALLERGY AND ALLERGIC ASTHMA.......................................................................................................................... 273 G.10 FORMOTEROL STUDY (NOVARTIS’S FORADIL) .......................................................................... 275 G.11 NOVARTIS’S FORADIL RECEIVES US APPROVAL FOR THE MAINTENANCE TREATMENT OF ASTHMA......................................................................................................................................... 276 G.12 GLAXOSMITHKLINE’S COMBINATION ASTHMA DRUG ADVAIR DISKUS ENTERED THE MARKET............................................................................................................................................... 277 LIST OF TABLES Table 1 Medical History........................................................................................................................... 189 Table 2 Historical Sales for Asthma Agents by Manufacturer and Brand 1996-2000 ($ In Millions) ..... 237 Table 3 Historical Sales of Anti-Inflammatory Asthma Drugs vs. Neurotransmission Regulators, 1994 - 2000 ($ Sales in Millions) .......................................................................................................... 238 Table 4 Product Development Activity for Asthma Therapy.................................................................... 256 ©2001 Adis International Inc., The Genesis Group. May not be reproduced without written permission. ASTHMA: OPINION LEADER FORUM EXPERT’S VIEWS AND PERSPECTIVE ON DIAGNOSIS, TREATMENT, PRODUCT PERFORMANCE…AND CLOSING THE NEED GAP LIST OF FIGURES Figure 1 Inflammatory Cascade in Asthma .................................................................................................. 12 Figure 2 Long-Term Control Medications.................................................................................................. 159 Figure 3 Quick-Relief Medications ............................................................................................................ 164 Figure 4 Classification of Severity of Asthma: Clinical Features before Treatment .................................. 168 Figure 5 Stepwise Approach for Managing Asthma in Adults and Children Older than 5 Years of Age: Treatments................................................................................................................................... 170 Figure 6 Algorithm for Diagnosing Asthma ............................................................................................... 191

Summary:

The subject of this report is the management of asthma in the United States. More specifically, however, the subject has been approached primarily through in-depth interviews (a forum) with clinical and academic authorities, managed care medical and disease management executives, and pharmaceutical industry and drug-delivery device manufacturer executives, so as to produce an audit of the current opinions and attitudes of the thought leaders in the user segments of the pharmaceutical and drug-delivery marketplace for asthma products