乾癬治療薬の世界市場予測・分析

◆英語タイトル:PharmaPoint: Psoriasis - Global Drug Forecast and Market Analysis to 2024
◆商品コード:GDHC119PIDR
◆発行会社(調査会社):GlobalData
◆発行日:2016年4月13日
◆ページ数:307
◆レポート言語:英語
◆レポート形式:PDF
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◆調査対象地域:グローバル
◆産業分野:製薬
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当調査レポートでは、乾癬治療薬の世界市場について調査・分析し、以下の構成でお届けいたします。
・イントロダクション
・乾癬の概要:病因、病態生理、症状
・疫学:リスク要因、併存症、グローバル動向、予測方法、疫学的予測結果
・乾癬の管理:治療概要、主要国における診断、診療状況
・乾癬治療薬の競争状況:製品概要、主要医薬品ブランド分析
・乾癬治療薬市場機会及びアンメット・ニーズ分析
・乾癬治療薬のパイプライン分析:主要国別治験動向、フェーズ別/進捗状況別治験動向、有望な薬剤
・製薬企業動向:戦略動向、主要企業情報
・乾癬治療薬市場展望:世界市場及び主要国の市場規模予測、成長要因、阻害要因
【レポートの概要】

PharmaPoint: Psoriasis – Global Drug Forecast and Market Analysis to 2024

Summary

Psoriasis (PsO) is an incurable genetic, systemic, inflammatory, and chronic skin disorder with an overall prevalence of 2-3% worldwide. Specifically, adult plaque psoriasis, the most common form of Psoriasis, is the focus of this report. Although not life-threatening, Psoriasis causes tremendous morbidity and personal angst for patients.

GlobalData projects the psoriasis market in 8MM to experience modest growth during the forecast period at a CAGR of 7.26%. This growth will be driven primarily by the highly anticipated arrivals of promising systemic therapies- interleukin-23 (IL-23) inhibitors (guselkumab and tildrakizumab), interleukin-17 (IL-17) inhibitors (Cosentyx, Taltz, and brodalumab) as well as phsophodiesterase (PDE4) inhibitor- Otezla (apremilast). Nevertheless, looming patent expiries of high-grossing branded drugs- especially TNF inhibitors, Humira, Enbrel and Remicade, in the US, 5EU (France, Germany, Italy, Spain, UK), and Japan, along with rapid global developments of biosimilars , are expected to spread the growth throughout the different classes of products, away from the branded TNF inhibitors which have traditionally been the main driver of growth in the prior years.

Highlights

Key Questions Answered

- How good is the management of Psoriasis with marketed therapies?
- Which drugs and players are important in the current management landscape?
- What are the most promising late-stage pipeline drugs and how will their launch shape the future treatment landscape in the Psoriasis market?
- What are the significant unmet needs and remaining opportunities in the Psoriasis market?
- What clinical and commercial factors are likely to uptake of Psoriasis therapies in the US, 5EU, Japan and India?

Key Findings

- The psoriasis market is currently very dynamic, with effective biologic therapies awaiting approval, such as interleukin-17 (IL-17) inhibitor- brodalumab, interleukin-23 (IL-23) inhibitors- guselkumab and tildrakizumab.
- Novel biologic therapies will challenge the current anti-TNF biologics in an attempt to dislodge their stronghold, if their safety and efficacy profiles are proven once they enter the market.
- The impending patent cliff for biologics will allow for the emergence of biosimilars to all the marketed biologic brands. Patent expiries take place during the forecast period for the current market leaders such as Johnson & Johnson’s Remicade (infliximab), AbbVie’s Humira (adalimumab), Amgen’s Enbrel (etanercept) and Johnson & Johnson’s Stelara (ustekinumab).
- The drivers for market growth will also include affordable treatments throughout the world, as well as the push for long-term drug efficacy. The main challenge for individual drugs will be to distinguish themselves in a crowded marketplace, comprising a highly diversified field of therapies, with existing drugs struggling to increase their patient share.

Scope

- Overview of Psoriasis, including epidemiology, etiology, pathophysiology, symptoms and current treatment options
- Topline Psoriasis market revenue from 2014-2024. Annual cost of therapy (ACOT) and major pipeline product sales in this forecast period are included.
- Key topics covered include strategic competitor assessment, unmet needs, pipeline assessment, and market outlook for the Psoriasis market.
- Pipeline analysis: comprehensive data split across different phases, emerging novel trends under development, synopses of innovative early-stage projects, and detailed analysis of late-stage pipeline products- including promising IL-17 and IL-23 inhibitors.
- Analysis of the current and future market competition in the global Psoriasis market (8MM). Insightful review of the key industry drivers, restraints and challenges. Each trend is independently researched to provide qualitative analysis of its implications.

Reasons to buy

The report will enable you to –
- Develop and design your in-licensing and out-licensing strategies through a review of pipeline products and technologies, and by identifying the companies with the most robust pipeline.
- Develop business strategies by understanding the trends shaping and driving the global Psoriasis market.
- Drive revenues by understanding the key trends, innovative products and technologies, market segments, and companies likely to impact the Psoriasis market in the future.
- Formulate effective sales and marketing strategies by understanding the competitive landscape and by analyzing the performance of various competitors.
- Identify emerging players with potentially strong product portfolios and create effective counter-strategies to gain a competitive advantage.
- Organize your sales and marketing efforts by identifying the market categories and segments that present maximum opportunities for consolidations, investments and strategic partnerships.

【レポートの目次】

1 Table of Contents
1 Table of Contents 9
1.1 List of Tables 15
1.2 List of Figures 21
2 Introduction 22
2.1 Catalyst 22
2.2 Related Reports 22
2.3 Upcoming Related Reports 23
3 Disease Overview 24
3.1 Etiology and Pathophysiology 24
3.1.1 Etiology 24
3.1.2 Pathophysiology 25
3.2 Symptoms 28
4 Epidemiology 30
4.1 Disease Background 30
4.2 Risk Factors and Comorbidities 30
4.3 Global Trends 31
4.3.1 Prevalence 31
4.4 Forecast Methodology 33
4.4.1 Sources Used for One-Year Diagnosed Prevalence of Psoriasis 35
4.4.2 Sources Not Used 37
4.4.3 Forecast Assumptions and Methods, One-Year Diagnosed Prevalent Cases of Psoriasis 38
4.5 Epidemiological Forecast for Psoriasis (2014-2024) 40
4.5.1 One-Year Diagnosed Prevalent Cases of Psoriasis 40
4.5.2 Age-Specific One-Year Diagnosed Prevalent Cases of Psoriasis 42
4.5.3 Sex-Specific One-Year Diagnosed Prevalent Cases of Psoriasis 44
4.5.4 Age-Standardized One-Year Diagnosed Prevalent Cases of Psoriasis 46
4.5.5 One-Year Diagnosed Prevalent Cases of Psoriasis by Severity 47
4.6 Discussion 48
4.6.1 Epidemiological Forecast Insight 48
4.6.2 Limitations of the Analysis 49
4.6.3 Strengths of the Analysis 49
5 Disease Management 50
5.1 Diagnosis and Treatment Overview 50
5.1.1 Diagnosis 50
5.1.2 Leading Prescribed Drugs and Treatment Guidelines 51
5.1.3 Clinical Practice 54
5.2 US 54
5.3 5EU 59
5.4 Japan 62
5.5 India 65
6 Competitive Assessment 67
6.1 Overview 67
6.2 Strategic Competitor Assessment 68
6.3 Product Profiles – Major Brands 69
6.3.1 Enbrel (Etanercept) 69
6.3.2 Humira (Adalimumab) 76
6.3.3 Remicade (Infliximab) 82
6.3.4 Stelara (Ustekinumab) 89
6.3.5 Cosentyx (Secukinumab) 95
6.3.6 Taltz (Ixekizumab) 103
6.3.7 Otezla (Apremilast) 112
6.3.8 Taclonex and Enstilar (Calcipotriene and Betamethasone Dipropionate) 117
6.3.9 Methotrexate 123
6.3.10 Fumaderm (Fumaric Acid Esters) 128
6.3.11 Alzumab (Itolizumab) 133
6.3.12 Other Therapeutic Drug Classes Used in Psoriasis 136
6.3.13 Non-pharmacological Therapy 137
7 Unmet Need and Opportunity 140
7.1 Overview 140
7.2 Limited Patient Access Due to Drug Reimbursement Pattern 140
7.2.1 Unmet Need 140
7.2.2 Gap Analysis 141
7.2.3 Opportunity 142
7.3 Improved Drug Safety and Efficacy Profiles 142
7.3.1 Unmet Need 142
7.3.2 Gap Analysis 143
7.3.3 Opportunity 143
7.4 Education and Treatment of Psychological Factors Accompanying Psoriasis 144
7.4.1 Unmet Need 144
7.4.2 Gap Analysis 145
7.4.3 Opportunity 145
7.5 Physician Education About the Different Types of Psoriasis, not Just Plaque Psoriasis 146
7.5.1 Unmet Need 146
7.5.2 Gap Analysis 146
7.5.3 Opportunity 147
8 Pipeline Assessment 148
8.1 Overview 148
8.2 Clinical Trial Mapping 149
8.2.1 Clinical Trials by Country 149
8.3 Clinical Trials by Phase and Trial Status 150
8.4 Promising Drugs in Clinical Development 151
8.4.1 Xeljanz (Tofacitinib) 153
8.4.2 Brodalumab 160
8.4.3 Guselkumab (CNTO-1959) 168
8.4.4 Tildrakizumab 173
8.4.5 Piclidenoson (CF-101) 180
8.4.6 Additional Phase III Pipeline Products 185
8.4.7 Phase II Pipeline Products 185
8.4.8 Phase I Pipeline Products 187
8.5 Biosimilar Pipeline Products 188
8.5.1 Introduction 188
8.5.2 Hospira’s Inflectra Versus J&J’s Remicade in Key Autoimmune Diseases 189
8.5.3 Biosimilars in the Immunology Community 189
8.5.4 By the Numbers: Biosimilars in Development 190
8.5.5 The Impact of Biosimilars Will be Felt Throughout the Pharmaceutical Industry 194
8.5.6 Uptake of Biosimilars for Psoriasis is Expected to Vary by Market 195
8.5.7 Biosimilars Forecast 197
9 Current and Future Players 202
9.1 Overview 202
9.2 Trends in Corporate Strategy 205
9.3 Company Profiles 207
9.3.1 Johnson & Johnson 207
9.3.2 AbbVie 209
9.3.3 Amgen 211
9.3.4 Novartis 213
9.3.5 Pfizer 216
9.3.6 Eli Lilly 217
9.3.7 Merck 219
9.3.8 LEO Pharma 221
9.3.9 Celgene 224
9.3.10 Can-Fite Biopharma 225
10 Market Outlook 228
10.1 Global Markets 228
10.1.1 Forecast 228
10.1.2 Drivers and Barriers – Global Issues 233
10.2 US 236
10.2.1 Forecast 236
10.2.2 Key Events 242
10.2.3 Drivers and Barriers 242
10.3 5EU 244
10.3.1 Forecast 244
10.3.2 Key Events 250
10.3.3 Drivers and Barriers 250
10.4 Japan 252
10.4.1 Forecast 252
10.4.2 Key Events 256
10.4.3 Drivers and Barriers 256
10.5 India 258
10.5.1 Forecast 258
10.5.2 Key Events 261
10.5.3 Drivers and Barriers 261
11 Appendix 264
11.1 Bibliography 264
11.2 Abbreviations 281
11.3 Methodology 286
11.4 Forecasting Methodology 286
11.4.1 Diagnosed Psoriasis Patients 286
11.4.2 Percent Drug-Treated Patients 287
11.4.3 Drugs Included in Each Therapeutic Class 287
11.4.4 Launch and Patent Expiry Dates 288
11.4.5 General Pricing Assumptions 289
11.4.6 Individual Drug Assumptions 290
11.4.7 Generic Erosion 298
11.4.8 Pricing of Pipeline agents 298
11.5 Physicians and Specialists Included in this Study 299
11.6 Primary Research – Prescriber Survey 302
11.7 About the Authors 303
11.7.1 Author 303
11.7.2 Reviewer 303
11.7.3 Epidemiologist 304
11.7.4 Global Director of Therapy Analysis and Epidemiology 304
11.7.5 Global Head of Healthcare 305
11.8 About GlobalData 306
11.9 Disclaimer 306

1.1 List of Tables
Table 1: Immune Cells Involved in Lesions 26
Table 2: Symptoms of Psoriasis 29
Table 3: Risk Factors and Comorbidities for Psoriasis 31
Table 4: 8MM, Global Trends for the Diagnosed Prevalence of Psoriasis 33
Table 5: 8MM, Sources of Epidemiological Data Used for the Forecast for Psoriasis One-Year Diagnosed Prevalent Cases 34
Table 6: 8MM, Sources of Epidemiological Data Used for the Segmentation of One-Year Diagnosed Prevalent Cases of Psoriasis by Severity 34
Table 7: 8MM, One-Year Diagnosed Prevalent Cases of Psoriasis, Both Sexes, All Ages, N, 2014-2024 41
Table 8: 8MM, Age-Specific One-Year Diagnosed Prevalent Cases of Psoriasis, Both Sexes, N (Row %), 2014 43
Table 9: 8MM, Sex-Specific One-Year Diagnosed Prevalent Cases of Psoriasis, All Ages, N (Row %), 2014 45
Table 10: Minimal Investigative Measures Required Before Prescribing Biologics for Psoriasis 52
Table 11: Top Three Biologics Prescribed for Moderate to Severe Psoriasis by Market, 2014 53
Table 12: Treatment Guidelines for Psoriasis 53
Table 13: Country Profile - US 58
Table 14: Country Profile - 5EU 61
Table 15: Country Profile - Japan 64
Table 16: Country Profile - India 66
Table 17: Leading Treatments for Psoriasis, 2015 69
Table 18: Product Profile - Enbrel 70
Table 19: Enbrel Pivotal Study I Outcomes at 3 and 6 Months 71
Table 20: Enbrel pivotal study II outcomes at 3 Months 72
Table 21: Long-Term Studies on Enbrel Efficacy in Treatment of Psoriasis 73
Table 22: Long-Term Safety Profile of Enbrel in the Treatment of Psoriasis 74
Table 23: Enbrel SWOT Analysis, 2015 75
Table 24: Global Sales Forecast ($m) for Enbrel, 2014-2024 76
Table 25: Product Profile - Humira 78
Table 26: Humira pivotal study outcomes at 16 weeks 79
Table 27: Humira SWOT Analysis, 2015 81
Table 28: Global Sales Forecast ($m) for Humira, 2014-2024 82
Table 29: Product Profile - Remicade 84
Table 30: Efficacy Results of RESTORE1 Trial of Remicade vs. MTX at Week 26 86
Table 31: Safety Results and AEs of RESTORE1 Trial of Remicade vs. MTX at Week 16 87
Table 32: Remicade SWOT Analysis, 2015 88
Table 33: Global Sales Forecast ($m) for Remicade, 2014-2024 89
Table 34: Product Profile - Stelara 91
Table 35: Stelara Pivotal Study Outcomes at Week 12 92
Table 36: Stelara SWOT Analysis, 2015 94
Table 37: Global Sales Forecast ($m) for Stelara, 2014-2024 95
Table 38: Product Profile - Cosentyx 97
Table 39: Efficacy Endpoints in Cosentyx Phase III ERASURE Study 98
Table 40: Efficacy End Points in Cosentyx Phase III FIXTURE study 99
Table 41: Cosentyx SWOT Analysis, 2015 102
Table 42: Global Sales Forecast ($m) for Cosentyx, 2014-2024 103
Table 43: Product Profile - Taltz 106
Table 44: Efficacy Results of UNCOVER-2 at Week 12 108
Table 45: Efficacy Results of UNCOVER-3 at Week 12 109
Table 46: Taltz SWOT Analysis, 2015 111
Table 47: Global Sales Forecast ($m) for Taltz, 2014-2024 112
Table 48: Product Profile - Otezla 114
Table 49: Otezla Efficacy Results at Week 16 in Studies ESTEEM-1 and ESTEEM-2 115
Table 50: Otezla SWOT Analysis, 2015 116
Table 51: Global Sales Forecast ($m) for Otezla, 2014-2024 117
Table 52: Product Profile - Taclonex/Enstilar 119
Table 53: Taclonex Efficacy Outcomes from Pivotal Phase III Studies for Adult Scalp and Body Psoriasis. 120
Table 54: Taclonex/Enstilar SWOT Analysis, 2015 122
Table 55: Global Sales Forecast ($m) for Taclonex/Daivobet/Dovobet, 2014-2024 123
Table 56: Product Profile - Methotrexate 125
Table 57: Methotrexate SWOT Analysis, 2015 127
Table 58: Global Sales Forecast ($m) for Methotrexate, 2014-2024 128
Table 59: Product Profile - Fumaderm 130
Table 60: Fumaderm SWOT Analysis, 2015 132
Table 61: Global Sales Forecast ($m) for Fumaderm, 2014-2024 133
Table 62: Product Profile - Alzumab 134
Table 63: Alzumab SWOT Analysis, 2013 135
Table 64: Global Sales Forecast ($m) for Alzumab, 2014-2024 136
Table 65: Summary of Minor Therapeutic Drug Classes for Psoriasis, 2015 137
Table 66: Dosing Guidelines for Broadband Ultraviolet B 139
Table 67: Dosing Guidelines for Narrowband Ultraviolet B 139
Table 68: Overall Unmet Needs in Psoriasis - Current Level of Attainment 140
Table 69: Psoriasis - Clinical Trials by Phase and Status, 2015 151
Table 70: Psoriasis - Phase Pipeline, 2015 151
Table 71: Comparison of Therapeutic Classes in Development for Psoriasis, 2015 153
Table 72: Product Profile - Xeljanz 155
Table 73: Xeljanz SWOT Analysis, 2015 159
Table 74: Global Sales Forecast ($m) for Xeljanz, 2014-2024 160
Table 75: Product Profile - Brodalumab 163
Table 76: Brodalumab SWOT Analysis, 2015 167
Table 77: Global Sales Forecast ($m) for Brodalumab, 2014-2024 168
Table 78: Product Profile - Guselkumab 169
Table 79: Guselkumab SWOT Analysis, 2015 172
Table 80: Global Sales Forecast ($m) for Guselkumab, 2014-2024 173
Table 81: Product Profile - Tildrakizumab 175
Table 82: Tildrakizumab SWOT Analysis, 2015 178
Table 83: Global Sales Forecast ($m) for Tildrakizumab, 2014-2024 179
Table 84: Product Profile - Piclidenoson (CF-101) 181
Table 85: Piclidenoson SWOT Analysis, 2015 184
Table 86: Additional Phase III Psoriasis Pipeline drugs, 2015 185
Table 87: Phase II Psoriasis Pipeline, 2015 185
Table 88: Phase I Psoriasis Pipeline, 2015 187
Table 89: Marketed and Pipeline Biosimilars for Psoriasis in the 8MM, 2015 192
Table 90: Physician Uptake of Biosimilar Products for Psoriasis Across the 8MM, 2015 197
Table 91: Global Sales Forecast ($m) for Etanercept Biosimilars, 2014-2024 197
Table 92: Global Sales Forecast ($m) for Adalimumab Biosimilars, 2014-2024 198
Table 93: Global Sales Forecast ($m) for Infliximab Biosimilars, 2014-2024 200
Table 94: Key Companies in the Psoriasis Market, 2015 204
Table 95: J&J’s Psoriasis Portfolio Assessment, 2015 208
Table 96: J&J’s Psoriasis Portfolio SWOT Analysis, 2015 209
Table 97: AbbVie’s Psoriasis Portfolio Assessment, 2015 211
Table 98: AbbVie’s Psoriasis SWOT Analysis, 2015 211
Table 99: Amgen’s Psoriasis Portfolio Assessment, 2015 213
Table 100: Amgen’s Psoriasis SWOT Analysis, 2015 213
Table 101: Novartis’s Psoriasis Portfolio Assessment, 2015 215
Table 102: Novartis’ Psoriasis SWOT Analysis, 2015 215
Table 103: Pfizer’s Psoriasis Portfolio Assessment, 2015 217
Table 104: Pfizer’s Psoriasis Portfolio SWOT Analysis, 2015 217
Table 105: Eli Lilly’s Psoriasis Portfolio Assessment, 2015 219
Table 106: Eli Lilly’s Psoriasis Portfolio SWOT Analysis, 2015 219
Table 107: Merck’s Psoriasis Portfolio Assessment, 2015 220
Table 108: Merck’s Psoriasis Portfolio SWOT Analysis, 2015 221
Table 109: LEO Pharma’s Psoriasis Portfolio Assessment, 2015 223
Table 110: LEO Pharma’s Psoriasis Portfolio SWOT Analysis, 2015 223
Table 111: Celgene’s Psoriasis Portfolio Assessment, 2015 224
Table 112: Celgene’s Psoriasis Portfolio SWOT Analysis, 2015 225
Table 113: Can-Fite’s Psoriasis Portfolio Assessment, 2015 226
Table 114: Celgene’s Psoriasis Portfolio SWOT Analysis, 2015 227
Table 115: Global Sales Forecast ($m) for Psoriasis, 2014-2024 230
Table 116: Global Psoriasis Market - Drivers and Barriers, 2014-2024 233
Table 117: Sales Forecast ($) for Psoriasis in the US, 2014-2024 239
Table 118: Key Events Impacting Sales for Psoriasis in the US, 2014-2024 242
Table 119: Psoriasis Market in the US - Drivers and Barriers, 2014-2024 242
Table 120: Sales Forecast ($) for Psoriasis in the 5EU, 2014-2024 247
Table 121: Key Events Impacting Sales for Psoriasis in the 5EU, 2014-2024 250
Table 122: Psoriasis Market in the 5EU - Drivers and Barriers, 2014-2024 250
Table 123: Sales Forecast ($) for Psoriasis in Japan, 2014-2024 254
Table 124: Key Events Impacting Sales for Psoriasis in Japan, 2014-2024 256
Table 125: Psoriasis Market in Japan - Drivers and Barriers, 2014-2024 256
Table 126: Sales Forecast ($) for Psoriasis in India, 2014-2024 259
Table 127: Key Events Impacting Sales for Psoriasis in India, 2014-2024 261
Table 128: Psoriasis Market in India - Drivers and Barriers, 2014-2024 261
Table 129: Key Launch Dates 288
Table 130: Key Patent Expiries 288
Table 131: Key Launch Dates 289
Table 132: Physicians Surveyed, by Country 302

1.2 List of Figures
Figure 1: Psoriatic Plaque on Elbow of Patient 25
Figure 2: The Three Layers of the Skin and Associated Structures 27
Figure 3: Healthy Skin Versus Psoriatic Skin 28
Figure 4: 8MM, One-Year Diagnosed Prevalent Cases of Psoriasis, Both Sexes, All Ages, N, 2014-2024 41
Figure 5: 8MM, Age-Specific One-Year Diagnosed Prevalent Cases of Psoriasis, Both Sexes, N, 2014 44
Figure 6: 8MM, Sex-Specific One-Year Diagnosed Prevalent Cases of Psoriasis, All Ages, N, 2014 46
Figure 7: 8MM, Age-Standardized One-Year Diagnosed Prevalent Cases of Psoriasis (%), All Ages, by Sex, 2014 47
Figure 8: 8MM, Severity Profile of One-Year Diagnosed Prevalent Cases of Psoriasis, All Ages, Both Sexes, N, 2014 48
Figure 9: Psoriasis Therapeutics - Ongoing Clinical Trial Sites by Country, 2015 150
Figure 10: Competitive Assessment of Late-Stage Pipeline Agents in Psoriasis, 2014-2024 152
Figure 11: Biosimilar Prescribing Habits in Psoriasis Across the 8MM, 2015 196
Figure 12: Global Sales Forecast ($m) for Enbrel vs. Etanercept Biosimilars, 2014-2024 198
Figure 13: Global Sales Forecast ($m) for Humira vs. Adalimumab Biosimilars, 2014-2024 199
Figure 14: Global Sales Forecast ($m) for Remicade vs. Infliximab Biosimilars, 2014-2024 201
Figure 15: Company Portfolio Gap Analysis in Psoriasis, 2014-2024 205
Figure 16: Global Sales for Psoriasis by Region, 2014-2024 232
Figure 17: Sales for Psoriasis in the US by Drug Class, 2014-2024 241
Figure 18: Sales for Psoriasis in the 5EU by Drug Class, 2014-2024 248
Figure 19: Sales for Psoriasis in the 5EU by Region, 2014-2024 249
Figure 20: Sales for Psoriasis in Japan by Drug Class, 2014-2024 255
Figure 21: Sales for Psoriasis in India by Drug Class, 2014-2024 260

【掲載企業】

Johnson & Johnson
AbbVie
Amgen
Novartis
Pfizer
Eli Lilly
Merck
LEO Pharma
Celgene
Can-Fite Biopharma

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