TABLE OF CONTENTS CHAPTER 1 INTRODUCTION 1 STUDY GOALS AND OBJECTIVES 1 REASONS FOR DOING THIS STUDY 1 INTENDED AUDIENCE 2 SCOPE OF REPORT 2 METHODOLOGY 2 INFORMATION SOURCES 2 ANALYST CREDENTIALS 3 RELATED BCC REPORTS 3 BCC ONLINE SERVICES 3 DISCLAIMER 3 CHAPTER 2 SUMMARY 5 SUMMARY TABLE GLOBAL MARKET FORECAST FOR HUMAN ANTIFUNGAL THERAPEUTICS BY GEOGRAPHIC REGION, THROUGH 2016 ($ MILLIONS) SUMMARY FIGURE GLOBAL SALES OF HUMAN ANTIFUNGALS, 2011 AND 2016 ($ MILLIONS) 6 5 CHAPTER 3 OVERVIEW 8 HISTORY AND CURRENT STATE OF ANTIFUNGALS 8 TYPES OF PATHOGENIC FUNGI 9 DEFINITION OF THE INDUSTRY 9 CONCEPTS IN THE INDUSTRY 9 IMPORTANCE OF THE INDUSTRY 10 PRODUCT LIFE CYCLES 11 TABLE 1 DRUG DEVELOPMENT LIFECYCLE FOLLOWING DISCOVERY OF NEW DRUG 12 DEVELOPMENT OF ANTIFUNGALS 12 FDA-APPROVED ANTIFUNGALS 13 AZOLE ANTIFUNGALS 13 ECHINOCANDINS 13 POLYENES 13 ALLYLAMINES 13 MISCELLANEOUS ANTIFUNGALS 14 FUTURE DEVELOPMENTS 14 HUMAN CLINICAL DEVELOPMENT, 2009 TO 2011 14 NEW DRUG ACTIVITY 15 TABLE 2 CLINICAL TRIALS OF ALL NEW DRUG THERAPIES AND COMBINATIONS BY ALL DATE FIELDS, 2009-2011 TABLE 3 SELECTED GLOBAL CLINICAL TRIALS OF ALL NEW DRUG THERAPIES THAT EITHER ARE COMPLETED OR ESTIMATED TO BE COMPLETED BETWEEN 2009 AND 2012 ACTIVE OR COMPLETED STUDIES POSTED OR UPDATED, 2009 TO 2011 16 TABLE 4 ACTIVE OR COMPLETED STUDIES, 2009-2011 16 16 16 CHAPTER 4 INTRODUCTION TO INDUSTRY APPLICATIONS OF ANTIFUNGAL MEDICINAL THERAPEUTICS SCOPE OF APPLICATIONS: HUMAN HEALTHCARE 20 HUMAN FUNGAL INFECTIONS 21 20
RISK FACTORS FOR DEVELOPING FUNGAL INFECTIONS 22 TABLE 5 RISK FACTORS ASSOCIATED WITH HUMAN FUNGAL INFECTIONS 23 FUNGAL SPECIES THAT CAUSE INFECTION IN HUMANS 24 Candidiasis 24 Cutaneous Candidiasis 26 Chronic Mucocutaneous Candidiasis 26 GI Tract Candidiasis 27 Respiratory Tract Candidiasis 27 Genitourinary Tract Candidiasis 27 Hepatosplenic Candidiasis 27 Systemic Candidiasis 27 Candidemia 28 Disseminated Candidiasis 28 Aspergillosis 29 Blastomycosis 30 Coccidioidomycosis 30 Cryptococcosis 31 Dermatophytosis 32 Histoplasmosis 33 Onychomycosis 34 Paracoccidioidomycosis 35 Pseudallescheriasis 35 Sporotrichosis 36 Zygomycosis 36 TABLE 6 INCIDENCE OF COMMON FUNGAL DISEASES 38 MORE RARE FUNGAL INFECTIONS AND DISORDERS 38 Literature Review 39 FUNGAL DRUG RESISTANCE 40 CURRENT DRUG RESISTANCE S: A GLOBAL VIEW 40 MDR SPECIES 41 Literature Review 43 TABLE 7 COMMON REASONS FOR FUNGAL RESISTANCE 44 STRATEGIES TO IMPROVE RESPONSE AND DECREASE MORTALITY 44 Literature Review 45 CHAPTER 5 HUMAN ANTIFUNGAL AGENTS 47 TABLE 8 GLOBAL MARKET FORECAST FOR HUMAN ANTIFUNGAL CONSUMPTION BY PRODUCT TYPE, THROUGH 2016 ($ MILLIONS) CLASSES OF ANTIFUNGALS 47 ECHINOCANDINS 47 Literature Review 48 AZOLES 48 Literature Review 49 POLYENES 49 Literature Review 49 OTHER 49 TABLE 9 GLOBAL ANTIFUNGAL PHARMACEUTICAL SALES: TRIAZOLES AND ECHINOCANDINS VERSUS OTHER ANTIFUNGALS THROUGH 2016 ($ MILLIONS) 47 50
TABLE 10 PHARMACEUTICAL ANTIFUNGALS BY CLASS/MECHANISM OF ACTION (%) 50 FIGURE 1 PERCENTAGE OF RECOGNIZED ANTIFUNGAL DRUGS (%) 50 TABLE 11 MAJOR ANTIFUNGAL AGENTS BY CLASS AND AVERAGE SALES PRICE PER DOSAGE, 2009 TABLE 12 FUNGAL INFECTION AND TRADITIONAL PHARMACEUTICAL REMEDY 53 TABLE 13 TYPE OF CANDIDAL INFECTION AND PHARMACEUTICAL TREATMENT 54 SIDE EFFECTS 54 TABLE 14 LIFE-THREATENING SIDE EFFECTS FROM ANTIFUNGAL PHARMACEUTICALS 56 OTC ANTIFUNGAL PREPARATIONS 56 TABLE 15 COMMON FUNGAL INFECTIONS AND OTC ROUTES OF ADMINISTRATION 58 NATURAL ANTIFUNGAL REMEDIES 58 TYPES OF NATURAL ANTIFUNGAL REMEDIES 59 Herbal Remedies 59 Enzyme-based Antifungal Agents 60 TABLE 16 COMMON NATURAL ANTIFUNGALS 61 SUMMARY OF SELECTED NATURAL ANTIFUNGALS 62 Aloe 62 Literature Review 63 Curcumin 63 Literature Review 64 Mint 64 Literature Review 64 Wild Marjoram 65 Literature Review 65 Radish 65 Literature Review 66 Parnafungins 66 Literature Review 67 Ginseng 67 Literature Review 68 Walnut 68 Literature Review 68 Pau d'arco 68 Literature Review 69 Garlic 69 Literature Review 69 Grapefruit Seed 70 Literature Review 70 Olive Leaf 70 Literature Review 70 Goldenseal 71 Literature Review 71 Oregano 71 Literature Review 71 Tea Tree 72 Literature Review 72 NATURAL REMEDIES IN EARLIER DEVELOPMENT 72 Literature Review 72 52
LABORATORY TESTING AND HISTOPATHOLOGY FOR FUNGAL INFECTIONS IN HUMANS Specimen Examination 74 Cultures 75 Blood Serology 75 ALTERNATIVE HEALTHCARE APPROACHES TO TESTING AND DIAGNOSIS OF FUNGAL INFECTIONS CAM Testing and Specialized Laboratories 75 Questionnaire for Symptoms 76 74 75 CHAPTER 6 COMMON ENVIRONMENTAL FUNGI 78 MOLDS AND THE HUMAN ISSUES THEY PRODUCE 78 WHY ENVIRONMENTAL MOLD IS A UNIQUE PROBLEM 79 HEALTH RISKS DUE TO ENVIRONMENTAL FUNGI AND MOLD 80 TABLE 17 COMMON HEALTH SYMPTOMS BASED ON ENVIRONMENTAL FUNGI AND MOLDS 81 TABLE 18 RISK FACTORS ASSOCIATION WITH ENVIRONMENTAL MOLD REACTIONS 81 TABLE 19 COMMON SOURCE LOCATIONS FOR ENVIRONMENTAL MOLDS 82 ENVIRONMENTAL MOLDS 82 ALTERNARIA 82 Literature Review 83 ASPERGILLUS 83 Literature Review 84 CLADOSPORIUM 84 Literature Review 85 PENICILLIUM 85 Literature Review 86 EUROTIUM 87 Literature Review 87 RHIZOPUS 87 Literature Review 87 MUCOR 88 Literature Review 88 GEOTRICHUM 88 Literature Review 88 FUSARIUM 89 Literature Review 89 STACHYBOTRYS 90 Literature Review 90 WALLEMIA 90 Literature Review 90 TRICHOTHECIUM 91 Literature Review 91 SCOPULARIOPSIS BREVICAULIS 91 Literature Review 91 SCYTALIDIUM DIMIDIATUM 92 Literature Review 92 TRICHODERMA 92 Literature Review 93
PAECILOMYCES VARIOTII 93 Literature Review 93 CHAPTER 7 GOVERNMENT REGULATORY AGENCIES AND PROFESSIONAL ASSOCIATIONS 96 GOVERNMENT REGULATIONS 96 FDA 96 TABLE 20 ANTIFUNGAL WARNING LETTERS FOR THE HUMAN SEGMENT FROM THE FDA TO MANUFACTURERS, 1997-2011 EPA 102 USDA 103 FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS 104 PROFESSIONAL ASSOCIATIONS 104 MEDICAL AND VETERINARY ASSOCIATIONS 104 AGRICULTURAL ASSOCIATIONS 104 OTHER ENVIRONMENTAL ASSOCIATIONS 104 97 CHAPTER 8 ANTIFUNGAL COMPANIES 107 HUMAN HEALTHCARE 107 PHARMACEUTICAL MANUFACTURERS 107 TABLE 21 MAJOR GLOBAL MANUFACTURERS OF HUMAN ANTIFUNGAL PHARMACEUTICALS 107 FIGURE 2 GLOBAL ANTIFUNGAL PHARMACEUTICAL MANUFACTURERS BY COUNTRY (%) 107 MAJOR PHARMACEUTICAL MANUFACTURER PROFILES 108 TABLE 22 COMPETITIVE MARKET SHARE BY PERCENT, 2011 (%) 109 FIGURE 3 COMPETITIVE MARKET SHARE BY PERCENT, 2011 (%) 109 Astellas Pharma, Inc. 109 Bayer HealthCare 110 Enzon Pharmaceuticals 110 Galderma Pharma SA/Galderma SA 110 Gilead Sciences, Inc. 111 Medicis Pharmaceutical Corp. 111 Novartis International AG 111 Pfizer, Inc. 112 Taro Pharmaceutical Industries, Ltd. 112 Teva Pharmaceutical Industries, Ltd. 112 OTC ANTIFUNGAL MANUFACTURERS 113 PHARMACEUTICAL OTC MARKET 113 TABLE 23 MAJOR HUMAN OTC ANTIFUNGAL MANUFACTURERS AND PRODUCTS 113 MAJOR PHARMACEUTICAL-BASED OTC MANUFACTURER PROFILES 114 Alva-Amco Pharmacal 114 Blaine Labs 114 Dartmouth Pharmaceuticals 115 Del Laboratories 115 Ganeden Biotech 115 Kramer Laboratories 115 Novartis International AG 116 Ortho McNeil 116 PEDiNOL Pharmacal, Inc. 116 Stiefel Laboratories 116
Tarmac Products 117 ALTERNATIVE OTC MANUFACTURERS 117 TABLE 24 COMMONLY AVAILABLE ALTERNATIVE ANTIFUNGALS 117 MAJOR ALTERNATIVE OTC MANUFACTURER PROFILES 118 AquaFlora 118 Crystal Star Herbal Nutrition 118 Enzymedica 118 Forest Herbs Research 119 Garden of Life 119 Michael s Naturopathic Programs 119 Nature s Plus 120 NOW Foods 120 Nutrition Now 120 PROSymbiotics 121 Pure Essence Laboratories 121 Rainbow Light 121 Renew Life 122 Solaray 122 Vitanica 122 CHAPTER 9 ANTIFUNGAL INDUSTRY 124 ANTIFUNGAL MARKET TRENDS: HUMAN HEALTHCARE 124 ACCELERATING ANTIFUNGAL DRUG DEVELOPMENT 124 TABLE 25 NEW PRESCRIPTION ANTIFUNGALS, 2005 JANUARY 2012 125 INCREASED TYPES OF TESTING 125 Need to Increase Use and Acceptance of Newer Drugs 126 EXPERIMENTAL RESEARCH: CLINICAL TRIALS PERFORMED AND SELECTED PRECLINICAL AND IN VIVO STUDIES A GENERAL OVERVIEW OF NON-PHARMACEUTICAL ANTIFUNGAL TECHNOLOGIES 127 Laser and Photodynamic Therapy 127 Studies 128 Literature Review 128 mabs 128 Diagnostics and Assays 129 Literature Review 129 Computer Modeling Technology 130 Literature Review 130 R&D SECTION: AN OVERVIEW OF PRODUCTS IN DEVELOPMENT 130 TABLE 26 ANTIFUNGALS IN DEVELOPMENT 131 TRENDS IN CLASS USED AND ADMINISTRATION METHOD 132 TABLE 27 PHARMACEUTICAL ANTIFUNGALS BY ROUTE OF ADMINISTRATION, 2011 (%) 133 FIGURE 4 PHARMACEUTICAL ANTIFUNGALS BY ROUTE OF ADMINISTRATION, 2011 (%) 133 TABLE 28 GLOBAL MARKET FORECAST FOR ANTIFUNGAL PHARMACEUTICAL PRODUCTS BY ROUTE OF ADMINISTRATION, THROUGH 2016 ($ MILLIONS) UTILIZATION OF OTC AND NATURAL/ALTERNATIVE ANTIFUNGAL AGENTS 134 Shifting Market From Prescription to OTC 134 Market Demand for OTC Products 134 126 133
CHAPTER 10 PATENT ANALYSIS 136 PURPOSE OF A PATENT ANALYSIS 136 DUE CARE IN REVIEWING THE PATENT ANALYSIS 136 NEW ANTIFUNGAL PATENTS ISSUED 136 TABLE 29 U.S. ANTIFUNGAL PATENT TRENDS, 1990-2009 (NUMBER OF PATENTS ISSUED) 137 TABLE 30 NEW U.S. ANTIFUNGAL PATENTS ISSUED, 2007 2012 137 TABLE 31 ASSIGNEES OF TWO OR MORE U.S. PATENTS FOR ANTIFUNGAL PRODUCTS, 2007-2011 TABLE 32 U.S. PATENT TRENDS BY COUNTRY, 2007-2011 (QUANTITY/%) 140 FIGURE 5 U.S. PATENT TRENDS BY COUNTRY, 2007-2011 (%) 141 TRENDS IN PATENT APPLICATIONS 141 TABLE 33 U.S. PATENT APPLICATIONS BY ANTIFUNGAL MECHANISM OF ACTION, 2007-2011 142 FIGURE 6 U.S. PATENT APPLICATIONS BY ANTIFUNGAL MECHANISM OF ACTION, 2007 THROUGH 2011 (%) TABLE 34 NEW U.S. PATENT APPLICATIONS, 2007-2011 143 TABLE 35 RECENT TRENDS IN PATENT APPLICATIONS FOR ANTIFUNGALS BY MECHANISM OF ACTION, 2007-2011 TABLE 36 U.S. PATENT APPLICATION TRENDS BY COUNTRY, 2007-2011 149 FIGURE 7 U.S. ANTIFUNGAL PATENT APPLICATIONS BY COUNTRY 2007-2011 (%) 149 PATENT EXPIRATIONS 150 TABLE 37 PATENT EXPIRATIONS 2006 2018 150 140 142 149 CHAPTER 11 APPENDIX 153 TABLE 38 PHARMACEUTICAL COMPANIES 153
LIST OF TABLES TABLE HEADING SUMMARY TABLE GLOBAL MARKET FORECAST FOR HUMAN ANTIFUNGAL THERAPEUTICS BY GEOGRAPHIC REGION, THROUGH 2016 ($ MILLIONS) TABLE 1 DRUG DEVELOPMENT LIFECYCLE FOLLOWING DISCOVERY OF NEW DRUG 12 TABLE 2 CLINICAL TRIALS OF ALL NEW DRUG THERAPIES AND COMBINATIONS BY ALL DATE FIELDS, 2009-2011 TABLE 3 SELECTED GLOBAL CLINICAL TRIALS OF ALL NEW DRUG THERAPIES THAT EITHER ARE COMPLETED OR ESTIMATED TO BE COMPLETED BETWEEN 2009 AND 2012 TABLE 4 ACTIVE OR COMPLETED STUDIES, 2009-2011 16 TABLE 5 RISK FACTORS ASSOCIATED WITH HUMAN FUNGAL INFECTIONS 23 TABLE 6 INCIDENCE OF COMMON FUNGAL DISEASES 38 TABLE 7 COMMON REASONS FOR FUNGAL RESISTANCE 44 TABLE 8 GLOBAL MARKET FORECAST FOR HUMAN ANTIFUNGAL CONSUMPTION BY PRODUCT TYPE, THROUGH 2016 ($ MILLIONS) TABLE 9 GLOBAL ANTIFUNGAL PHARMACEUTICAL SALES: TRIAZOLES AND ECHINOCANDINS VERSUS OTHER ANTIFUNGALS THROUGH 2016 ($ MILLIONS) TABLE 10 PHARMACEUTICAL ANTIFUNGALS BY CLASS/MECHANISM OF ACTION (%) 50 TABLE 11 MAJOR ANTIFUNGAL AGENTS BY CLASS AND AVERAGE SALES PRICE PER DOSAGE, 2009 TABLE 12 FUNGAL INFECTION AND TRADITIONAL PHARMACEUTICAL REMEDY 53 TABLE 13 TYPE OF CANDIDAL INFECTION AND PHARMACEUTICAL TREATMENT 54 TABLE 14 LIFE-THREATENING SIDE EFFECTS FROM ANTIFUNGAL PHARMACEUTICALS 56 TABLE 15 COMMON FUNGAL INFECTIONS AND OTC ROUTES OF ADMINISTRATION 58 TABLE 16 COMMON NATURAL ANTIFUNGALS 61 TABLE 17 COMMON HEALTH SYMPTOMS BASED ON ENVIRONMENTAL FUNGI AND MOLDS 81 TABLE 18 RISK FACTORS ASSOCIATION WITH ENVIRONMENTAL MOLD REACTIONS 81 TABLE 19 COMMON SOURCE LOCATIONS FOR ENVIRONMENTAL MOLDS 82 TABLE 20 ANTIFUNGAL WARNING LETTERS FOR THE HUMAN SEGMENT FROM THE FDA TO MANUFACTURERS, 1997-2011 TABLE 21 MAJOR GLOBAL MANUFACTURERS OF HUMAN ANTIFUNGAL PHARMACEUTICALS 107 TABLE 22 COMPETITIVE MARKET SHARE BY PERCENT, 2011 (%) 109 TABLE 23 MAJOR HUMAN OTC ANTIFUNGAL MANUFACTURERS AND PRODUCTS 113 TABLE 24 COMMONLY AVAILABLE ALTERNATIVE ANTIFUNGALS 117 TABLE 25 NEW PRESCRIPTION ANTIFUNGALS, 2005 JANUARY 2012 125 TABLE 26 ANTIFUNGALS IN DEVELOPMENT 131 TABLE 27 PHARMACEUTICAL ANTIFUNGALS BY ROUTE OF ADMINISTRATION, 2011 (%) 133 TABLE 28 GLOBAL MARKET FORECAST FOR ANTIFUNGAL PHARMACEUTICAL PRODUCTS BY ROUTE OF ADMINISTRATION, THROUGH 2016 ($ MILLIONS) TABLE 29 U.S. ANTIFUNGAL PATENT TRENDS, 1990-2009 (NUMBER OF PATENTS ISSUED) 137 TABLE 30 NEW U.S. ANTIFUNGAL PATENTS ISSUED, 2007 2012 137 TABLE 31 ASSIGNEES OF TWO OR MORE U.S. PATENTS FOR ANTIFUNGAL PRODUCTS, 2007-2011 TABLE 32 U.S. PATENT TRENDS BY COUNTRY, 2007-2011 (QUANTITY/%) 140 TABLE 33 U.S. PATENT APPLICATIONS BY ANTIFUNGAL MECHANISM OF ACTION, 2007-2011 142 TABLE 34 NEW U.S. PATENT APPLICATIONS, 2007-2011 143 TABLE 35 RECENT TRENDS IN PATENT APPLICATIONS FOR ANTIFUNGALS BY MECHANISM OF ACTION, 2007-2011 TABLE 36 U.S. PATENT APPLICATION TRENDS BY COUNTRY, 2007-2011 149 TABLE 37 PATENT EXPIRATIONS 2006 2018 150 5 16 16 47 50 52 97 133 140 149
TABLE HEADING TABLE 38 PHARMACEUTICAL COMPANIES 153
LIST OF FIGURES FIGURE TITLE SUMMARY FIGURE GLOBAL SALES OF HUMAN ANTIFUNGALS, 2011 AND 2016 ($ MILLIONS) 6 FIGURE 1 PERCENTAGE OF RECOGNIZED ANTIFUNGAL DRUGS (%) 50 FIGURE 2 GLOBAL ANTIFUNGAL PHARMACEUTICAL MANUFACTURERS BY COUNTRY (%) 107 FIGURE 3 COMPETITIVE MARKET SHARE BY PERCENT, 2011 (%) 109 FIGURE 4 PHARMACEUTICAL ANTIFUNGALS BY ROUTE OF ADMINISTRATION, 2011 (%) 133 FIGURE 5 U.S. PATENT TRENDS BY COUNTRY, 2007-2011 (%) 141 FIGURE 6 U.S. PATENT APPLICATIONS BY ANTIFUNGAL MECHANISM OF ACTION, 2007 THROUGH 2011 (%) FIGURE 7 U.S. ANTIFUNGAL PATENT APPLICATIONS BY COUNTRY 2007-2011 (%) 149 142