Protein Drugs: Global Markets and Manufacturing Technologies

Protein Drugs: Global Markets and Manufacturing Technologies published by BCC Research in October, 2008. This report consists of 136 pages and the price starts from US $ 4850.

Introduction

Abstract

STUDY GOALS AND OBJECTIVES

Protein drugs have received enormous attention from pharmaceutical companies due to a combination of their bioreactivity, specificity, safety and overall success rate. Yet there are still improvements to be made, especially with respect to their formulation and delivery method. Advances in protein drug delivery are certain to increase patient compliance and expand many drug markets.

REASONS FOR DOING THE STUDY

Although the drug development industry still focuses primarily on small molecules, in recent years protein and peptide therapeutics comprise a significant percent of the product line and pipeline for most major pharmaceutical companies. Peptide and protein therapeutics, especially antibody drugs, are attractive due to their high specificity and potency and low incidence of toxicity. Developments in manufacturing, including transgenic, recombinant and synthetic methods, have been key as protein drugs have moved into the mainstream. A previous report by BCC, Protein Drugs in 2003, discussed the early days of these manufacturing improvements and focused on emerging recombinant methods of protein production.

Recombinant protein technologies are now standard and the current focus has shifted from the method of bulk production to post-production techniques that promise to enhance stability and delivery. In the effort to produce orally available therapeutics, formulation issues have become critical.

SCOPE OF REPORT

In this report, we analyze the markets for each major class of protein therapeutic monoclonal antibodies, cytokines, peptide hormones, vaccines and blood products. We examine the current successes, including the size of the global market and the sales forecast for each class through 2013. Where appropriate, we break down the markets further to examine the major individual protein drugs in the class. We discuss challenges such as delivery methods, and side effects and consider issues of add-on products and patent protection.

INTENDED AUDIENCE

This study will be of interest to individuals involved in the design, manufacture, and marketing of next-generation pharmaceuticals. Venture capitalists, entrepreneurs, medical analysts, and research directors with an interest in the protein and peptide drug industry will find this research valuable. Those involved in the development of novel formulations and chemical modifications will also find a comprehensive discussion of the challenges and advances in the field.

INFORMATION SOURCES

This report has been assembled following an in-depth analysis of primary and secondary data. Primary research was conducted via telephone interviews with industry professionals, research scientists, physician-researchers, and laboratory heads to discover the most recent developments in their fields of interest. Secondary data was collected via a comprehensive search of the scientific, peer-reviewed literature, clinical trial reports and databases, industry trade media, company websites, annual reports, and industry press releases.

The market assessments provided have been assembled based on publicly available information up to and including August 2008. The base year for this report is 2008 and forecast data are provided through 2013. In many cases, figures for 2008 were not yet released and in these cases figures were extrapolated from 2007 statistics, half-year projections for 2008, and historical trends. Market figures are based on current dollars and inflation is not computed into the projection figures.

ANALYST CREDENTIALS

Amy Brock has over 12 years of research experience working at the interface of the biological sciences, bioengineering, and biophysics. Trained at the Massachusetts Institute of Technology and Harvard University, she holds a B.S. and Ph.D. in biomedical science. She is the author of Pharmacogenomics: New Technologies in the Development of Personalized Therapies; Kinase Inhibitors in Clinical Use; and Genetic Diseases and Medical Imaging.

Table of Contents

Chapter 1: SUMMARY 2

• SUMMARY TABLE GLOBAL MARKET FOR PROTEIN THERAPEUTICS, THROUGH 2013 ($ MILLIONS) 4
• SUMMARY TABLE (CONTINUED) 5
• SUMMARY FIGURE GLOBAL MARKET FOR PROTEIN THERAPEUTICS, 2007-2013 ($ MILLIONS)

Chapter 2: OVERVIEW 7

• DEFINING THE TERMS: PROTEINS AND PEPTIDES 6
• PROTEIN DRUGS: THEN AND NOW 7
• TABLE 1 NEW DRUGS ENTERING CLINICAL TRIALS, BY TYPE, 2007 8
• DRUG ADMINISTRATION: MILESTONES AND CHALLENGES 9
• PEGYLATION 10
• PEPTIDE-MEDIATED RECEPTOR TARGETING 11
• PATIENT COMPLIANCE 11
• Patient Compliance (Continued)

Chapter 3: MARKETS BY PRODUCTS 42

• TABLE 2 GLOBAL SIZE OF PROTEIN DRUGS MARKET BY PRODUCTS, THROUGH 2013 ($ MILLIONS) 13
• FIGURE 1 GLOBAL SIZE OF PROTEIN DRUGS MARKET BY PRODUCTS, 2008 AND 2013 ($ MILLIONS) 14
• FIGURE 2 GLOBAL SHARE OF PROTEIN DRUGS MARKET BY PRODUCT, 2008 (%) 14
• FIGURE 2 (CONTINUED) 15
• FIGURE 3 GLOBAL SHARE OF PROTEIN DRUGS MARKET BY PRODUCT, 2013 (%) 15
• ANTIBODY DRUGS 16
• PRODUCTION OF ANTIBODIES FOR THERAPY 16
• Murine Monoclonal Antibodies 17
• Chimeric and Humanized Monoclonal Antibodies 17
• Human Monoclonal Antibodies 18
• Antibody-directed Enzyme Prodrug Therapy (ADEPT) 18
• HOW ANTIBODY DRUGS WORK 18
• How Antibody Drugs Work (Continued) 19
• TABLE 3 FDA-APPROVED MONOCLONAL ANTIBODIES, 2008 20
• THE ANTIBODY DRUG MARKET 21
• TABLE 4 GLOBAL MARKET FORECAST FOR ANTIBODY DRUG PRODUCTS, THROUGH 2013 ($ MILLIONS) 21
• FIGURE 4 GLOBAL MARKET FOR ANTIBODY DRUGS, 2008 (%) 21
• FIGURE 4 (CONTINUED) 22
• FIGURE 5 GLOBAL MARKET FOR ANTIBODY DRUGS, 2013 (%) 22
• FIGURE 5 (CONTINUED) 23
• CHANGES IN A DYNAMIC MARKET 23
• Possible new indications for Campath 23
• EGF-R Antibodies: Still Investigational Therapies 24
• Side Effects Could Affect Tysabri' s Future 25
• TABLE 5 FDA-APPROVED MONOCLONAL ANTIBODIES FOR CANCER TREATMENT, 2008 26
• CYTOKINES 27
• THE CYTOKINE MARKET 28
• Granulocyte-colony Stimulating Factors 28
• Interferon 28
• Interferon 28
• Interferon 29
• Interleukins 29
• TABLE 6 GLOBAL MARKET FORECAST FOR CYTOKINE PRODUCTS, THROUGH 2013 ($ MILLIONS) 30
• FIGURE 6 GLOBAL MARKET FOR CYTOKINE DRUGS, 2008 (%) 30
• FIGURE 7 FORECAST GLOBAL MARKET FOR CYTOKINE DRUGS, 2013 (%) 31
• PEPTIDE HORMONES 32
• TABLE 7 GLOBAL MARKET FORECAST FOR PEPTIDE HORMONES, THROUGH 2013 ($ MILLIONS) 33
• FIGURE 8 GLOBAL MARKET FORECAST FOR PEPTIDE HORMONES, 2008 AND 2013 ($ MILLIONS) 33
• FIGURE 9 GLOBAL MARKET FORECAST FOR PEPTIDE HORMONES, 2008 (%) 34
• VACCINES 34
• KINDS OF VACCINES 35
• Killed Whole Organisms 36
• Attenuated Organisms 36
• Toxoids 36
• Surface Proteins 36
• Inactivated Virus 37
• Attenuated Virus 37
• TABLE 8 VACCINE PREPARATIONS, BY DISEASE 37
• TABLE 9 VACCINE-PREVENTABLE DISEASE IN THE U.S., PRE- AND POST- VACCINATION PROGRAMS 38
• THE GLOBAL PROTEIN VACCINE MARKET 39
• TABLE 10 GLOBAL MARKET FORECAST FOR VACCINES, THROUGH 2013 ($ MILLIONS) 39
• FIGURE 10 GLOBAL MARKET FORECAST FOR VACCINES, 2008 AND 2013 ($ MILLIONS) 40
• TABLE 11 NEW AND EMERGING VACCINE PRODUCTS 41
• BLOOD PRODUCTS 42
• WHAT DRIVES DEMAND FOR BLOOD PRODUCTS 42
• THE GLOBAL MARKET FOR BLOOD PRODUCTS 43
• TABLE 12 GLOBAL MARKET FORECAST FOR BLOOD PRODUCTS, THROUGH 2013 ($ MILLIONS) 44
• FIGURE 11 GLOBAL MARKET FORECAST FOR BLOOD PRODUCTS, 2008 AND 2013 ($ MILLIONS) 44
• FIGURE 12 GLOBAL MARKET FOR BLOOD PRODUCTS, 2008 (%) 45
• Recombinant Albumin 45
• Factor VIII 46
• TABLE 13 COMPANIES INVOLVED IN FACTOR VIII DEVELOPMENT 46
• Factor IX 46
• Hemoglobin 47
• Second Generation Hemoglobins in Development 48
• TABLE 14 COMPANIES INVOLVED IN RECOMBINANT HEMOGLOBIN MANUFACTURE 49
• Protein C 49
• PEPTIDE ANTIBIOTICS 50
• TYPES OF PEPTIDE ANTIBIOTICS 50
• TABLE 15 GLOBAL MARKET FORECAST FOR PEPTIDE ANTIBIOTICS, THROUGH 2013 51
• THE RESISTANCE PROBLEM 51
• THERAPEUTIC ENZYMES 52
• Glucocerebrosidase 52
• Tissue Plasminogen Activator 53
• Pancreatin 53
• Thrombin 53
• TABLE 16 GLOBAL MARKET FORECAST FOR THERAPEUTIC ENZYMES, THROUGH 2013

Chapter 4: MANUFACTURING TECHNOLOGY 25

• NATURAL SOURCING AND EXTRACTION 55
• HUMAN SOURCING 56
• SPECIAL FEATURES OF HUMAN-SOURCING MANUFACTURE 56
• TABLE 17 PROTEIN DRUGS MADE BY HUMAN-SOURCE EXTRACTION 56
• SPECIAL FEATURES OF ANIMAL SOURCING MANUFACTURE 57
• TABLE 18 PROTEIN DRUGS MADE BY NATURAL ANIMAL-SOURCE EXTRACTION 58
• TABLE 19 PROTEIN DRUGS MANUFACTURED BY NATURAL SOURCING AND EXTRACTION, BY PRODUCT, THROUGH 2013 ($ MILLIONS) 58
• FIGURE 13 PROTEIN DRUGS MANUFACTURED BY NATURAL SOURCING AND EXTRACTION, BY PRODUCT, 2008 AND 2013 ($ MILLIONS) 59
• FIGURE 14 PROTEIN DRUGS MANUFACTURED BY NATURAL SOURCING AND EXTRACTION, BY PRODUCT 2008 (%) 59
• FIGURE 15 PROTEIN DRUGS MANUFACTURED BY NATURAL SOURCING AND EXTRACTION, BY PRODUCT, 2013 (%) 60
• MICROBIAL FERMENTATION 60
• TABLE 20 PROTEIN DRUGS MANUFACTURED BY MICROBIAL FERMENTATION, BY PRODUCT, THROUGH 2013 ($ MILLIONS) 61
• FIGURE 16 PROTEIN DRUGS MANUFACTURED BY MICROBIAL FERMENTATION, BY PRODUCT, 2008 AND 2013 ($ MILLIONS) 62
• FIGURE 17 PROTEIN DRUGS MANUFACTURED BY MICROBIAL FERMENTATION, BY PRODUCT, 2008 (%) 62
• FIGURE 18 PROTEIN DRUGS MANUFACTURED BY MICROBIAL FERMENTATION, BY PRODUCT, 2013 (%) 63
• MAMMALIAN CELL CULTURE 63
• BIOREACTORS 64
• TABLE 21 TYPES OF BIOREACTORS 64
• Bioreactors (Continued) 65
• OTHER CELL CULTURE SYSTEMS: INSECT CELLS 66
• TABLE 22 PROTEIN DRUGS MANUFACTURED BY CELL CULTURE, BY PRODUCT, THROUGH 2013 ($ MILLIONS) 66
• FIGURE 19 PROTEIN DRUGS MANUFACTURED BY CELL CULTURE, BY PRODUCT, 2008 AND 2013 ($ MILLIONS) 67
• FIGURE 20 PROTEIN DRUGS MANUFACTURED BY CELL CULTURE, 2008 (%) 67
• FIGURE 21 PROJECTED PROTEIN DRUGS MANUFACTURED BY CELL CULTURE, 2013 (%) 68
• TRANSGENICS: PLANTS AND ANIMALS 68
• TRANSGENIC PLANTS PHARMING 68
• TABLE 23 TRANSGENIC PLANT PHARMACEUTICALS UNDER DEVELOPMENT 69
• TRANSGENIC ANIMALS 70
• Founder Animal Production 70
• History in the Making: the First Transgenic Drugs 71
• TABLE 24 PROTEIN DRUGS MANUFACTURED BY TRANSGENICS, BY PRODUCT, THROUGH 2013 ($ MILLIONS) 72
• FIGURE 22 PROTEIN DRUGS MANUFACTURED BY TRANSGENICS, BY PRODUCT, THROUGH 2013 73
• FIGURE 23 PROTEIN DRUGS MANUFACTURED BY TRANSGENICS, BY PRODUCT, 2013 (%) 73
• TABLE 25 PROTEIN DRUGS DERIVED FROM TRANSGENIC ANIMALS, 2008 74
• On the Horizon: Gene Therapy with Transgenics? 74
• CHEMICAL SYNTHESIS 75
• HOW IT WORKS 75
• COST AND SCALING- UP 76
• TABLE 26 PEPTIDE PHARMACEUTICALS MANUFACTURED BY CHEMICAL SYNTHESIS 77
• TABLE 27 PROTEIN DRUGS MANUFACTURED BY CHEMICAL SYNTHESIS, BY PRODUCT TYPE, THROUGH 2013 ($ MILLIONS) 77
• FIGURE 24 PROTEIN DRUGS MANUFACTURED BY CHEMICAL SYNTHESIS, BY PRODUCT TYPE, THROUGH 2013 ($ MILLIONS) 78
• FIGURE 25 PROTEIN DRUGS MANUFACTURED BY CHEMICAL SYNTHESIS, BY PRODUCT TYPE, 2008 78
• FIGURE 26 PROTEIN DRUGS MANUFACTURED BY CHEMICAL SYNTHESIS, BY PRODUCT TYPE, 2013

Chapter 5: TECHNOLOGY 16

• MANUFACTURING, PROCESSING AND FORMULATION 80
• FIGURE 27 MANUFACTURING PROCESS FLOW CHART 80
• PROCESSING AND DOWNSTREAM 81
• PROTEIN AGGREGATION HAS CLINICAL RAMIFICATIONS 82
• FOCUS ON FORMULATION 83
• FREEZE-THAW 83
• Challenges in the Freezing Process 84
• Thawing 85
• Freeze-Thaw Technologies 85
• FORMULATION STEP 86
• Formulation Step (Continued) 87
• FILTRATION 88
• DRUG PRODUCT FILLING 88
• LYOPHILIZATION 89
• Lyophilization (Continued) 90
• Lyophilization (Continued) 91
• INSPECTION AND PACKAGING 92
• DRUG STORAGE, TRANSPORT AND DELIVERY 92
• Protein-Silicone Oil Interactions 92
• Leachables and Extractables 93
• TRANSPORTATION 94
• PHOTOSTABILITY 95

Chapter 6: PATENT ANALYSIS 8

• PATENTS BY PRODUCT TYPE 96
• TABLE 28 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY TECHNOLOGY, AUGUST 2005 TO AUGUST 2008 96
• FIGURE 28 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY PRODUCT, AUGUST 2005 TO AUGUST 2008 97
• PATENTS BY REGION 97
• TABLE 29 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY REGION, AUGUST 2005 TO AUGUST 2008 97
• TABLE 29 (CONTINUED) 98
• TABLE 30 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY TECHNOLOGY, AUGUST 2005 TO AUGUST 2008 98
• FIGURE 29 PROTEIN PHARMACEUTICALS, ISSUED PATENTS BY TECHNOLOGY, AUGUST 2005 TO AUGUST 2008 (%) 99
• IMPORTANT PATENT ISSUES FOR FOLLOW-ON BIOLOGICS 99
• PATENTS OF INTEREST IN THE PROTEIN DRUGS FIELD 100
• TREATMENTS USING TRANSGENIC GOAT PRODUCED ANTITHROMBIN III 100
• HIGHLY PHOSPHORYLATED AND SULFATED RECOMBINANT FACTOR IX 101
• HEPATITIS C RECEPTOR PROTEIN CD81 101
• PURIFICATION OF POLYPEPTIDES 102
• Purification of Polypeptides (Continued) 103

Chapter 7: INTERNATIONAL ASPECTS 3

• TABLE 31 GLOBAL PROTEIN THERAPEUTIC MARKET PRODUCTION BY REGION, 2008 ($ MILLIONS) 104
• UNITED STATES 105
• WESTERN EUROPE 105
• JAPAN 105
• CHINA 106

Chapter 8: MARKET SHARE 3

• TABLE 32 MARKET SHARE OF COMPANIES INVOLVED IN ANTIBODY DRUGS, 2008 (UNIT, %) 107
• TABLE 33 MARKET SHARE OF COMPANIES INVOLVED IN CYTOKINES, 2008 (UNIT, %) 108
• TABLE 34 MARKET SHARE OF COMPANIES INVOLVED IN PEPTIDE HORMONES, 2008 (UNIT, %) 108
• TABLE 35 MARKET SHARE OF COMPANIES INVOLVED IN VACCINES, 2008 (UNIT, %) 108
• TABLE 36 MARKET SHARE OF COMPANIES INVOLVED IN BLOOD PRODUCTS, 2008 (UNIT, %) 109
• TABLE 37 MARKET SHARE OF COMPANIES INVOLVED PEPTIDE ANTIBIOTICS, 2008 (UNIT, %) 109
• TABLE 38 MARKET SHARE OF COMPANIES INVOLVED ENZYMES, 2008 (UNIT, %) 109

Chapter 9: COMPANY PROFILES 28

• ABBOTT LABORATORIES 110
• TABLE 39 ABBOTT LABS PROTEIN DRUGS 111
• AEGIS THERAPEUTICS 111
• ALEXION PHARMACEUTICALS 112
• AMGEN 113
• TABLE 40 AMGEN' S PROTEIN DRUGS 114
• BAYER DIAGNOSTICS 114
• BIOGEN IDEC, INC. 115
• TABLE 41 BIOGEN IDEC' S PROTEIN DRUGS 116
• CENTOCOR 116
• ELI LILLY & CO. 117
• TABLE 42 LILLY' S PROTEIN DRUGS 118
• GENENTECH, INC. 118
• TABLE 43 GENENTECH' S PROTEIN DRUGS 119
• GENZYME CORP. 119
• TABLE 44 GENZYME CORPORATION PROTEIN DRUGS 120
• TABLE 44 (CONTINUED) 121
• JOHNSON & JOHNSON INC. 121
• MEDIMMUNE, INC. 122
• MEDAREX 122
• TABLE 45 MEDAREX' S PIPELINE PROTEIN DRUGS 123
• MERCK & CO., INC. 124
• TABLE 46 MERCK' S PROTEIN DRUGS 124
• MERCK SERONO 125
• TABLE 47 MERCK-SERONO' S PROTEIN DRUGS 126
• NOVARTIS PHARMA AG 126
• TABLE 48 NOVARTIS' PROTEIN DRUGS 127
• NOVO NORDISK A/S 127
• NOVO NORDISK A/S (CONTINUED) 128
• ROCHE HOLDINGS, LTD. 129
• TABLE 49 ROCHE' S PROTEIN DRUGS 130
• SANGART 131
• SANOFI-AVENTIS 131
• UNIGENE LABORATORIES, INC. 132
• UNIGENE LABORATORIES, INC. (CONTINUED) 133
• VACCINOGEN INC 134
• WYETH 135
• WYETH (CONTINUED) 136
• TABLE 50 WYETH' PROTEIN DRUGS 137

Chapter 10: APPENDIX: WEB RESOURCES FOR PROTEIN DRUG DESIGN

• THE NATIONAL CANCER INSTITUTE 3D STRUCTURE DATABASE 138
• KIBANK 138
• COMBINATORIAL CHEMISTRY REVIEW 138
• GDB: STRUCTURES 139

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