The Cancer Market Outlook to Competitive landscape, market size, pipeline analysis, and growth opportunities

Transcription

1 The Cancer Market Outlook to 2016 Competitive landscape, market size, pipeline analysis, and growth opportunities Reference Code: BI Publication Date: June

2 About Business Insights Business Insights has a team of in-house pharmaceutical and regulatory analysts drawn from consulting, R&D and competitive intelligence life sciences backgrounds. Our analysts specialize in providing detailed insight into the future of therapeutic drug markets and emerging pharmaceutical markets and have extensive analytical, forecasting and research experience in the pharmaceutical, biotech and outsourcing sectors. Our team maintains regular contact with industry executives to track market developments, and they base their market models on a wide range of proprietary drug sales, pipeline and epidemiological databases to provide up-to-date, accurate strategic insight on the future of the pharmaceutical market. Disclaimer Copyright 2011 Business Insights Ltd This report is published by Business Insights (the Publisher). This report contains information from reputable sources and although reasonable efforts have been made to publish accurate information, you assume sole responsibility for the selection, suitability and use of this report and acknowledge that the Publisher makes no warranties (either express or implied) as to, nor accepts liability for, the accuracy or fitness for a particular purpose of the information or advice contained herein. The Publisher wishes to make it clear that any views or opinions expressed in this report by individual authors or contributors are their personal views and opinions and do not necessarily reflect the views/opinions of the Publisher. 2

3 Table of Contents About Business Insights 2 Disclaimer 2 Executive summary 15 Overview and epidemiology of cancer 15 Global market analysis 16 Pipeline analysis 16 Competitive landscape 17 Chapter 1 Overview and epidemiology of cancer 19 Summary 19 Introduction 20 Overview 20 Cancer risk factors 20 Chemical carcinogens 20 Age 21 Tobacco smoke 21 Lifestyle factors 21 Radiation 21 Immune system 21 Genetics 21 Lung cancer 22 Overview 22 Adenocarcinoma 22 Squamous-cell carcinoma 22 3

4 Large-cell carcinoma 22 Small-cell lung cancer 22 Diagnosis, treatment, and management 23 Epidemiology 24 NSCLC 24 SCLC 25 Forecast epidemiology 25 NSCLC 25 SCLC 27 Colorectal cancer 29 Overview 29 Diagnosis, treatment, and management 29 Epidemiology 30 Forecast epidemiology 31 Breast cancer 33 Overview 33 Diagnosis, treatment, and management 33 Epidemiology 34 Forecast epidemiology 35 Ovarian cancer 37 Overview 37 Diagnosis, treatment, and management 37 Epidemiology 38 Forecast epidemiology 38 Uterine and cervical cancer 40 Overview 40 Diagnosis, treatment, and management 40 Epidemiology 41 4

5 Forecast epidemiology 41 Leukemia 43 Overview 43 Diagnosis, treatment, and management 44 Epidemiology 44 Forecast epidemiology 45 Prostate cancer 47 Overview 47 Diagnosis, treatment, and management 47 Epidemiology 48 Forecast epidemiology 49 Pancreatic cancer 50 Overview 50 Diagnosis, treatment, and management 50 Epidemiology 50 Forecast epidemiology 51 Lymphomas 53 Overview 53 Diagnosis, treatment, and management 53 Epidemiology 54 Forecast epidemiology 55 Head and neck cancer 57 Overview 57 Diagnosis, treatment, and management 58 Epidemiology 58 Forecast epidemiology 59 5

6 Chapter 2 Global market analysis 61 Summary 61 Introduction 62 Market analysis by country 62 Market analysis by drug class 64 Leading brand dynamics 64 Avastin (bevacizumab) Roche 65 Herceptin (trastuzumab) Roche 67 MabThera (rituximab) Roche 68 Gleevec/Glivec (imatinib) Novartis 69 Taxotere (docetaxel) Sanofi 70 Alimta (pemetrexed) Eli Lilly 71 Key recent events in the cancer market 71 Amgen/Takeda s motesanib fails Phase III trial in lung cancer 71 Merck Serono files expanded approval for Erbitux (cetuximab) in the EU 72 Abbott signs a deal with Seattle Genetics for antibody drug conjugate (ADC) technology 72 Strides carboplatin approved in European markets 73 Herceptin receives approval for gastric cancer in Japan 73 NICE revises its decision for MabThera as a maintenance treatment 74 Antineoplastics 74 Competitive dynamics of antineoplastics 74 Leading antineoplastic brands 75 Antineoplastic mab market analysis 77 Market dynamics 77 Key brands analysis 77 Antineoplastic sales forecast 77 Cytostatic hormonal therapies 79 6

7 Competitive dynamics of cytostatic hormonal therapies 79 Leading brands of cytostatic hormonal therapies 79 Arimidex (anastrozole) AstraZeneca 80 Femara (letrozole) Novartis 81 Lupron Depot (leuprorelin) Takeda 81 Zoladex (goserelin) AstraZeneca 82 Cytostatic hormonal therapy sales forecast 82 Global cancer market sales forecast 83 Chapter 3 Pipeline analysis 85 Summary 85 Introduction 86 Key trends in R&D 86 Targeted therapies are changing the treatment regimen of cancer 86 Cancer vaccines enhance the body s immune response 87 Pricing is becoming a major issue for cancer patients 87 Combination treatments are becoming the treatment of choice 88 Oncology pipeline 89 Leading drugs in development 90 Recently approved/marketed drugs 92 Afinitor (everolimus) Novartis 92 Provenge (sipuleucel-t) Dendreon 93 Votrient (pazopanib) GSK 96 Zytiga (abiraterone) Johnson & Johnson (J&J) 98 Yervoy (ipilimumab) Bristol-Myers Squib (BMS) 100 Arzerra (ofatumumab) GSK/Genmab 103 Phase III compounds 105 Zelboraf (vemurafenib) Roche/Plexxikon 105 Trastuzumab emtansine (T-DM1) Roche 106 Crizotinib (PF ) Pfizer 109 Iniparib (BSI-201) Sanofi 112 7

8 Omnitarg (pertuzumab) Roche 113 Stimuvax (emepepimut-s) Merck Serono 115 Aflibercept Sanofi 116 Allovectin (velimogene aliplasmid) Vical 119 Perifosine (KRX 0401) Keryx 121 Ruxolitinib (INCB18424) Incyte 123 MDV3100 Medivation 125 Bosutinib Pfizer 127 Axitinib (AG013736) Pfizer 129 Pipeline forecast of leading drugs in development 131 Chapter 4 Competitive landscape 132 Summary 132 Introduction 132 Sales performance of leading players 133 Roche 134 Sales focus by drug class 134 Regional sales distribution 135 Leading products 135 Pipeline analysis 137 Strategic and growth analysis 139 Drivers of growth 139 Resistors of growth 140 Novartis 141 Sales focus by drug class 141 Regional sales distribution 141 Leading products 142 Pipeline analysis 143 Strategic and growth analysis 144 Drivers of growth 144 8

9 Resistors of growth 145 AstraZeneca 145 Sales focus by drug class 145 Regional sales distribution 146 Leading products 147 Pipeline analysis 147 Strategic and growth analysis 148 Drivers of growth 148 Resistors of growth 150 Sanofi 150 Sales focus by drug class 150 Regional sales distribution 151 Leading products 151 Pipeline analysis 152 Strategic and growth analysis 154 Drivers of growth 154 Resistors of growth 155 Eli Lilly 155 Sales focus by drug class 155 Regional sales distribution 155 Leading products 156 Pipeline analysis 157 Strategic and growth analysis 158 Drivers of growth 158 Resistors of growth 159 Appendix 160 Scope 160 9

10 Methodology 161 Market size methodology 161 Epidemiology 161 Market forecast 161 Glossary/Abbreviations 162 Trial expansions 164 References 166 Journal articles 166 Clinical trials 166 Important websites

11 Table of figures Figure 1: Treatment of lung cancer by stage 23 Figure 2: Types of breast cancers 33 Figure 3: Types of leukemia 43 Figure 4: Chemotherapy options for Hodgkin s disease 54 Figure 5: Head and neck cancers and their risk factors 57 Figure 6: Cancer market share by region (%), Figure 7: Current pharmacological treatment options for cancer 89 Figure 8: Oncology pipeline by indication and stage of development, Figure 9: Key drugs in late-stage development or recently launched 91 11

12 Table of tables Table 1: Estimated prevalence of NSCLC across the 7MM, Table 2: Estimated prevalence of SCLC across the 7MM, Table 3: Forecast epidemiology of NSCLC across the 7MM, Table 4: Forecast epidemiology of SCLC across the 7MM, Table 5: Estimated prevalence of CRC across the 7MM, Table 6: Forecast epidemiology of CRC across the 7MM, Table 7: Estimated prevalence of breast cancer across the 7MM, Table 8: Forecast epidemiology of breast cancer across the 7MM, Table 9: Estimated prevalence of ovarian cancer across the 7MM, Table 10: Forecast epidemiology of ovarian cancer across the 7MM, Table 11: Estimated prevalence of uterine and cervical cancer across the 7MM, Table 12: Forecast epidemiology of uterine and cervical cancer across the 7MM, Table 13: Estimated prevalence of leukaemia across the 7MM, Table 14: Forecast epidemiology of leukemia across the 7MM, Table 15: Estimated prevalence of prostate cancer across the 7MM, Table 16: Forecast epidemiology of prostate cancer across the 7MM, Table 17: Estimated prevalence of pancreatic cancer across the 7MM, Table 18: Forecast epidemiology of pancreatic cancer across the 7MM, Table 19: Estimated prevalence of lymphomas across the 7MM, Table 20: Forecast epidemiology of lymphomas across the 7MM, Table 21: Estimated prevalence of head and neck cancers across the 7MM, Table 22: Forecast epidemiology of head and neck cancers across the 7MM, Table 23: Global cancer market share by geography ($m), Table 24: Global cancer market by drug class ($m), Table 25: Sales of leading brands in the global cancer market ($m), Table 26: Sales of leading brands in the global antineoplastics market ($m), Table 27: Antineoplastic sales forecast ($m), Table 28: Sales of leading brands in the global cytostatic hormonal therapies market ($m), Table 29: Cytostatic hormonal therapy sales forecast ($m), Table 30: Global cancer market sales forecast ($m), Table 31: Overview of Afinitor 92 Table 32: Overview of Provenge 93 Table 33: Key recent trials with Provenge 95 12

13 Table 34: Overview of Votrient 96 Table 35: Key recent trials with Votrient 97 Table 36: Overview of Zytiga 98 Table 37: Key recent trials with Zytiga 99 Table 38: Overview of Yervoy 100 Table 39: Key recent trials with Yervoy 102 Table 40: Overview of Arzerra 103 Table 41: Key recent trials with Arzerra 104 Table 42: Overview of vemurafenib 105 Table 43: Overview of trastuzumab emtansine 106 Table 44: Key recent trials with trastuzumab emtansine 108 Table 45: Overview of crizotinib 109 Table 46: Key recent trials with crizotinib 111 Table 47: Overview of iniparib 112 Table 48: Overview of Omnitarg 113 Table 49: Key recent trials with Omnitarg 114 Table 50: Overview of Stimuvax 115 Table 51: Overview of aflibercept 116 Table 52: Key recent trials with aflibercept 118 Table 53: Overview of Allovectin 119 Table 54: Key recent trials with Allovectin 120 Table 55: Overview of perifosine 121 Table 56: Key recent trials with perifosine 122 Table 57: Overview of ruxolitinib 123 Table 58: Key recent trials with ruxolitinib 124 Table 59: Overview of MDV Table 60: Key recent trials with MDV Table 61: Overview of bosutinib 127 Table 62: Key recent trials with bosutinib 128 Table 63: Overview of axitinib 129 Table 64: Key recent trials with axitinib 130 Table 65: Sales forecast for leading drugs in development ($m), Table 66: Sales of leading players in the global cancer market ($m), Table 67: Roche cancer sales by drug class ($m), Table 68: Roche regional sales distribution ($m), Table 69: Roche sales of leading cancer products ($m),

14 Table 70: Roche late-stage cancer R&D pipeline, April Table 71: Novartis cancer sales by drug class ($m), Table 72: Novartis regional sales distribution ($m), Table 73: Novartis sales of leading cancer products ($m), Table 74: Novartis late-stage cancer R&D pipeline, Table 75: AstraZeneca cancer sales by drug class ($m), Table 76: AstraZeneca regional sales distribution ($m), Table 77: AstraZeneca leading cancer products ($m), Table 78: AstraZeneca late-stage cancer R&D pipeline, January Table 79: Sanofi cancer sales by drug class ($m), Table 80: Sanofi regional sales distribution ($m), Table 81: Sanofi leading cancer products ($m), Table 82: Sanofi late-stage cancer R&D pipeline, February Table 83: Eli Lilly cancer sales by drug class ($m), Table 84: Eli Lilly regional sales distribution ($m), Table 85: Eli Lilly sales of leading cancer products ($m), Table 86: Eli Lilly late-stage cancer R&D pipeline, January

15 Executive summary Overview and epidemiology of cancer Global cancer prevalence rates are on the rise owing to an aging population and changing lifestyle. Prevalence data is influenced by the increasing diagnosis and survival rates across the global market. Globally, lung cancer is one of the most common types of cancer, with an estimated 1.2 million new cases being diagnosed every year. Among all lung cancer cases, approximately 42% survive after one year, yet the relative five-year survival rate for all lung cancers combined is approximately 15% only. The last decade has seen a significant fall in mortality rates from breast cancer. Owing to the lack of medical treatments for late-stage breast cancer, the long-term survival of patients still depends on early diagnosis, which has been improved through the contentious use of large-scale screening and public awareness programs. Prostate cancer is one of the most commonly diagnosed cancers and is the second leading cancerrelated cause of death in men, surpassed only by lung cancer. The highest incidence of this disease is seen in the US, and studies have placed black men at a higher risk of prostate cancer than men from other ethnic origins. Globally, colorectal cancer (CRC) is the second most commonly diagnosed form of cancer. In 2010, approximately 1.6 million individuals were affected by CRC in the seven major markets (7MM). The incidence of CRC increases with age, generally occurring in the sixth or seventh decade of life. Mortality rates, particularly among men, appear set to rise steadily over the next five years, despite the positive impact of screening on the early identification of the disease. Pancreatic cancer is most common in men and women between the ages of 60 and 75, making age the predominant risk factor for incidence of the disease. In the seven major markets, prevalence is projected to grow modestly to 68 million in The low prevalence of the disease can be attributed to late diagnosis, poor prognosis, and low survival. 15

16 Global market analysis The global cancer market in 2010 was valued at $54bn, an increase of 5.1% over the previous year s sales of $51.3bn, and is forecasted to grow at a CAGR of 6.9% from , reaching $81bn in Collectively, the seven major markets (US, 5EU, and Japan) represented 79.1% (or $43bn) of in the global cancer market in In terms of size, the US dominated the global cancer market, with 2010 sales of $21bn and a market share of 38.5%. The global cancer market is becoming increasingly competitive, with two therapeutic classes, namely antineoplastics and cytostatic hormonal treatments, dominating this sector. Collectively, the leading 10 brands accounted for almost 58.2% (or $31.4bn) of the global cancer market in In 2010 antineoplastics was the leading drug class in the global cancer market. The global antineoplastics market was valued at $46bn in 2010 at a year-on-year (Y-o-Y) growth of 7.3%. The major drugs that contributed to the 2010 sales in the antineoplastics category were Roche s Avastin (bevacizumab) at $6.2bn, Herceptin (trastuzumab) at $5.2bn, and MabThera (rituximab) at $5.1bn, with Y-o-Y sales growth of 3.8%, 3.1%, and 3.3% respectively. The cytostatic hormonal market registered 2010 sales of $8bn at a Y-o-Y decline of 6.5%. AstraZeneca s Arimidex (anastrozole) and Novartis s Femara (letrozole) led this class, reaching sales of $1.5bn and $1.3bn respectively in Pipeline analysis Oncology has become one of the major focus areas for pharmaceutical and biotechnology companies because of the high unmet need for improved treatments for multiple types of cancer. Targeted therapies are revolutionizing the paradigm of cancer treatment and are likely to be used in most cancer patients in the next 10 years. Due to the high incidence and subsequent potential for market success, breast cancer and NSCLC continue to drive high levels of R&D (along with indications such as NHL, RCC, CML, and prostate cancer). 16

17 Another factor that plays a major role in the growth of the cancer therapy market is the expansion of target indications. Most of the blockbuster drugs were launched for a narrow indication, and were later approved for other indications. A classic example is imatinib, which was first approved by the FDA in 2001 for the treatment of CML, and later expanded to nine different indications. Regardless of indication, the key challenge in ensuring the commercial success of pipeline drugs is to ascertain their integration into current treatment regimens either in combination with existing therapies or by demonstrating significant superiority over current treatments. Pricing risk remains the key investment concern in cancer. Moreover, the level of scrutiny by payers regarding the cost-effectiveness of cancer treatments has further intensified in recent years. In the US and UK, new products are assessed on the basis of their clinical efficacy versus cost. For instance, the National Institute for Health and Clinical Excellence (NICE) has recommended the National Health Service (NHS) to pay only when the price for innovation is in proportion to what it delivers. Although a large number of cancer vaccines are in development, Dendreon s Provenge (sipuleucel-t) is the first therapeutic cancer vaccine approved in the US (April 2010) for the treatment of prostate cancer. Competitive landscape In 2010, the leading 10 companies of the global cancer market represented 87.1% (or $47bn) of the total market. The combined sales accrued from these companies expanded at 5.9% for Roche led the global cancer market with 2010 sales of $20.6bn, which was mainly based on sales from Avastin, Herceptin, MabThera, and Xeloda. Novartis reported 2010 sales of $6bn, representing an increase of 14.4% over the previous year, which positions it as the second largest pharmaceutical company in the global cancer market. Novartis s cancer business includes two major drugs, namely Gleevec/Glivec and Femara 17

18 AstraZeneca was the third largest company among the global cancer players in 2010, with sales of $3.9bn at a Y-o-Y decline of 12%. The decline in sales is largely due to the 31.4% and 21.3% slump in Casodex and Arimidex sales respectively resulting from generics entering the market. Sanofi is positioned as the fourth largest company in the global cancer market, registering 2010 sales of $3.4bn at a Y-o-Y decline of 16%. This decline was primarily due to intense generic competition of its blockbuster colon cancer treatment Eloxatine, which recorded a significant Y-o-Y decline of 55.4% to reach $566m in Eli Lilly recorded an increase in sales of 8.4% to $3.4bn in 2009 and became the fifth largest company in the global cancer market, based on the strong sales performance of its key products such as Alimta ($2.2bn) and gemcitabine ($1.1bn). 18

19 Chapter 1 Overview and epidemiology of cancer Summary Global cancer prevalence rates are on the rise owing to an aging population and changing lifestyle. Prevalence data is influenced by the increasing diagnosis and survival rates across the global market. Globally, lung cancer is one of the most common types of cancer, with an estimated 1.2 million new cases being diagnosed every year. Among all lung cancer cases, approximately 42% survive after one year, yet the relative five-year survival rate for all lung cancers combined is approximately 15% only. The last decade has seen a significant fall in mortality rates from breast cancer. Owing to the lack of medical treatments for late-stage breast cancer, the long-term survival of patients still depends on early diagnosis, which has been improved through the contentious use of large-scale screening and public awareness programs. Prostate cancer is one of the most commonly diagnosed cancers and is the second leading cancerrelated cause of death in men, surpassed only by lung cancer. The highest incidence of this disease is seen in the US, and studies have placed black men at a higher risk of prostate cancer than men from other ethnic origins. Globally, colorectal cancer (CRC) is the second most commonly diagnosed form of cancer. In 2010, approximately 1.6 million individuals were affected by CRC in the seven major markets (7MM). The incidence of CRC increases with age, generally occurring in the sixth or seventh decade of life. Mortality rates, particularly among men, appear set to rise steadily over the next five years, despite the positive impact of screening on the early identification of the disease. Pancreatic cancer is most common in men and women between the ages of 60 and 75, making age the predominant risk factor for incidence of the disease. In the seven major markets, prevalence is projected to grow modestly to 68 million in The low prevalence of the disease can be attributed to late diagnosis, poor prognosis, and low survival. 19

20 Introduction This chapter provides a background to the cancer therapeutic area in terms of the major indications covered in this report, an overview of each of the indications, diagnosis, management and treatment, incidence and prevalence data, and forecast epidemiology data to The cancer types covered in this report are those that are highly prevalent and commonly treated through pharmacological therapy, namely lung cancer, colorectal cancer (CRC), lymphomas, leukemia, breast cancer, ovarian cancer, uterine cancer, prostate cancer, and pancreatic cancer. This chapter provides specific information on these cancer types across the seven major markets (7MM), with current diagnosis and treatment techniques. The 10 types of cancer selected in this report are those that feature major drug-dependent treatment regimens rather than those which entail surgery-based treatment regimens. Overview Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. If the spread is not controlled, it can result in death. Cancer is caused by both external factors (tobacco, chemicals, radiation, and infectious organisms) and internal factors (inherited gene mutations, immune conditions, hormones, and random mutations). These causal factors may act together or in sequence to initiate or promote carcinogenesis. Depending on the stage of the disease, cancer can be treated by surgery, radiation, chemotherapy, hormone therapy, biological therapy, and targeted therapy. Cancer risk factors There are several risk factors that can lead to cancer. Some of the major ones are described in the following sections. Chemical carcinogens A carcinogen is any substance (e.g. a chemical or radiation particle) that can damage a cell and make it more likely to turn cancerous. Examples of chemical carcinogens are inhaled asbestos and certain dioxins; examples of radiation are gamma rays and alpha particles. 20

21 Age The risk of developing cancer increases with age. This is probably due to an accumulation of damaged cells in the body over time. Eventually one damaged cell may manage to survive and multiply, out of control, into a cancer. Tobacco smoke Tobacco smokers are more likely to develop cancer of the lungs, mouth, throat, esophagus, bladder, or pancreas. Lifestyle factors Diet and other lifestyle factors may increase or decrease the risk of developing cancer. Radiation Radiation is carcinogenic. For example, exposure to radioactive materials and nuclear fallout can increase the risk of leukemia and other cancers. Sun exposure and sunburn (radiation from ultraviolet A or B rays) can increases the risk of developing skin cancer. Immune system A deficient immune system (such as that of people with AIDS or on immunosuppressive therapy) increases the risk of developing certain cancers. Genetics Some cancers have a strong genetic link. For example, in certain childhood cancers an abnormal gene or genes may trigger a cell to become abnormal and cancerous. However, regular screening examinations by a healthcare professional can result in the detection and removal of precancerous growths, as well as the diagnosis of cancers at an early stage. Such screening examinations also help to detect cancers of the colon, rectum, breast, prostate, and skin in early stages. 21

22 Lung cancer Overview Globally, lung cancer is one of the most common types of cancer. The epidemic of lung cancer has been identified as a major health issue confronting both developed and developing countries, with the disease featuring high mortality rates across all countries. Lung cancer is a malignant tumor that develops from the uncontrolled growth of lung cells, which if left untreated can metastasize to the liver, brain, bones, and eventually throughout the body. There are two main types of lung cancer: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). NSCLC is the third largest cancer market in terms of numbers of patients diagnosed. There are three main types of NSCLC, which are described in the following sections. Adenocarcinoma This develops from the cells which produce mucus (phlegm) in the lining of the airways. This type of cancer is the most common and represents 40% to 50% of the NSCLC patient population. It is characterized by originating near the gas exchange surface of the lung and is most commonly caused by smoking. Squamous-cell carcinoma This is the second most common type of lung cancer. It develops in the cells that line the airways. This type of lung cancer is often caused by smoking and accounts for approximately 20 25% of NSCLC cases. Large-cell carcinoma The final NSCLC subtype is large-cell carcinoma, which grows at an accelerated rate near the surface of the lung. It is sometimes known as undifferentiated carcinoma. Small-cell lung cancer Small-cell lung cancer (SCLC), also known as oat-cell carcinoma is a less common form of lung cancer. It has its origins in the larger breathing tubes and grows rapidly, becomes large in size, and metastasizes to other parts of the body at an early stage. NSCLC and SCLC grow and spread in different ways and therefore have different treatment procedures. 22

23 Diagnosis, treatment, and management Usually symptoms of lung cancer do not appear until the disease is in its advanced stages. But some lung cancers are diagnosed early, and are often found as a result of tests for other medical conditions, mainly through chest X-rays. Clinical manifestations of lung cancer are dependent on the location of the tumor and the extent of metastasis. The most common symptoms of local-regional cancer include coughing, dyspnea, hemoptysis, wheezing, chest pain, and pneumonia. Figure 1 illustrates the treatment of lung cancer according to the growth stage. Figure 1: Treatment of lung cancer by stage Stage Primary treatment Adjuvant therapy Five-year survival rate (%) Non-small-cell lung cancer (NSCLC) I Resection Chemotherapy 60 to 70 IIA IIIA (resectable) IIIA (unresectable) or IIIB (involvement of contralateral lymph nodes) IIIB (pleural effusion) or IV Resection Resection with or without preoperative chemotherapy Chemotherapy with concurrent or subsequent radiotherapay Chemotherapy or resection of primary brain metastasis and primary T1 tumor Chemotherapy with or without radiation therapy Chemotherapy with or without radiation therapy 40 to to 30 None 10 to 20 None 10 to 15 (two year survival) Small-cell lung cancer (SCLC) Limited disease Chemotherapy with concurrent radiotherapy None 15 to 25 Extensive disease Chemotherapy None < 5 Source: Spira and Ettinger,

24 The treatment for lung cancer depends on several different factors, such as the stage at which the cancer is discovered, its form, and the age and general medical state of the patient. Typical treatments can involve some combination of surgery, chemotherapy, and radiation therapy. When discovered early enough, surgery with adjuvant chemotherapy represents the best prognosis. The surgical procedures performed are lobectomy (removal of one lobe), bilobectomy (both lobes), and pneumectomy (removal of whole lung). Sometimes radical radiotherapy with curative intent is used instead of surgery to treat local disease. For SCLC, etoposide or ifosfamide is typically added to a platinum analog to comprise the standard chemotherapy treatment regimen. Radiotherapy represents another treatment option for patients and is given in conjunction with chemotherapy to patients who are not eligible for surgery. The standard first-line chemotherapy in NSCLC in the US is carboplatin/paclitaxel, but in Europe oncologists favor cisplatin/gemzar (gemcitabine). Epidemiology NSCLC According to the International Agency for Research on Cancer (IARC) GLOBOCAN 2008 database, NSCLC accounts for approximately 80% of all lung cancers. Table 1 details the prevalence of NSCLC. Table 1: Estimated prevalence of NSCLC across the 7MM, 2010 Country Prevalence (000s) Prevalence (%) Share (%) France Germany Italy Spain UK EU US Japan Total Source: IARC GLOBOCAN 2008; Business Insights analysis 24

25 SCLC SCLC generally has a more rapid growth and earlier development of widespread metastases, accounting for about 20% of new lung cancer cases diagnosed per year. Because of its propensity to grow rapidly, SCLC is highly sensitive to initial chemotherapy and radiotherapy. Based on the IARC GLOBOCAN 2008 database, approximately 125,130 individuals are estimated to have been suffering from SCLC across the seven major markets in Table 2 details the SCLC epidemiology. Table 2: Estimated prevalence of SCLC across the 7MM, 2010 Country Prevalence (000s) Prevalence (%) Share (%) France Germany Italy Spain UK EU US Japan Total Source: IARC GLOBOCAN 2008; Business Insights analysis Forecast epidemiology NSCLC In 2010, in the 7MM (7 major markets: US, Japan, France, Germany, Italy, Spain, UK), there were approximately 501,180 individuals affected with NSCLC, which is projected to grow modestly to around 514,220 by 2016, as shown in Table 3. The primary risk factor for NSCLC is smoking, which is responsible for more than 85% of deaths related to lung cancer. 25

26 Table 3: Forecast epidemiology of NSCLC across the 7MM, Country France Prevalence (000s) Prevalence (%) Germany Prevalence (000s) Prevalence (%) Italy Prevalence (000s) Prevalence (%) Spain Prevalence (000s) Prevalence (%) UK Prevalence (000s) Prevalence (%) EU5 Prevalence (000s) Prevalence (%) US Prevalence (000s) Prevalence (%) Japan Prevalence (000s) Prevalence (%) Total Total Prevalence (000s) Total Prevalence (%) Source: IARC GLOBOCAN 2008; Business Insights analysis 26

27 SCLC According to Business Insights estimates, the 2010 prevalence population of approximately 125,130 in the seven major markets is projected to grow modestly through to 2016 (see Table 4). Despite high initial responses to chemotherapy and radiotherapy, most SCLC patients die from recurrent disease. 27

28 Table 4: Forecast epidemiology of SCLC across the 7MM, Country France Prevalence (000s) Prevalence (%) Germany Prevalence (000s) Prevalence (%) Italy Prevalence (000s) Prevalence (%) Spain Prevalence (000s) Prevalence (%) UK Prevalence (000s) Prevalence (%) EU5 Prevalence (000s) Prevalence (%) US Prevalence (000s) Prevalence (%) Japan Prevalence (000s) Prevalence (%) Total Prevalence (000s) Prevalence (%) Source: IARC GLOBOCAN 2008; Business Insights analysis 28

29 Colorectal cancer Overview Colorectal cancer (CRC) is the second largest market in terms of numbers of patients diagnosed. According to IARC GLOBOCON 2008, in the 7MM (7 major markets: US, Japan, France, Germany, Italy, Spain, UK) it is estimated that over 583,040 patients per year are diagnosed with CRC. Of these, about 20% are diagnosed with metastatic disease. Most cases of colon cancer begin as small, non-cancerous (benign) clumps of cells called adenomatous polyps. Over a period of time, some of these polyps become colon cancers. Regular screening tests can help prevent colon cancer by identifying polyps before they become cancerous. If signs and symptoms of colon cancer do appear, they may include changes in bowel habits, blood in the stool, persistent cramping, gas, or abdominal pain. The incidence of colon cancer increases with age, generally occurring in the sixth or seventh decade of life. While age is a major factor in the incidence of CRC, sedentary lifestyle, low fiber diets, diets rich in red and processed meat, excessive alcohol intake, inflammatory bowel conditions, radiation exposure, and related medical conditions are associated with an increased risk. A genetic basis for CRC has been observed in those who have had a family history of colon cancer or have a family history of familial adenomatous polyposis (FAP) or hereditary non-polyposis CRC (HNPCC). Diagnosis, treatment, and management CRC can take many years to develop, and early detection greatly improves the chances of a cure. Diagnosis involves screening in asymptomatic patients with no family history of CRC and is recommended in patients aged 50 years and over in most of the developed pharmaceutical markets. Diagnostic tests include colonoscopy, sigmoidoscopy, digital rectal exams (DRE) and fecal occult blood tests (FOBT). However, both DRE and FOBT are associated with low levels of reliability, and double-contrast barium enema and flexible sigmoidoscopy are used in patients suspected of having a tumor or a precursory condition. Such techniques provide an accurate diagnosis in an estimated 90% of cases. 29

30 Treatment depends partly on the stage of the cancer. There are three standard treatment options: surgery to remove cancer cells chemotherapy to kill cancer cells radiation therapy to destroy cancerous tissue. Stage 0 colon cancer may be treated by removing the cancer cells, often during a colonoscopy. For stage I, II, and III cancer, more extensive surgery is needed to remove the part of the colon that is cancerous. Surgery remains the primary treatment for CRC, while chemotherapy and/or radiotherapy, depending on the patient s staging and overall medical condition, may be recommended. A local excision procedure known as polypectomy (polyp removal) is recommended in early stage cancer. More advanced CRC will typically involve removal of sections of the colon (colectomy) or rerouting of the intestine by colostomy. Chemotherapy is also used to treat patients with stage IV colon cancer. Irinotecan, oxaliplatin, and 5- fluorouracil are the three most commonly used drugs. In addition, monoclonal antibodies, including cetuximab (Erbitux), panitumumab (Vectibix), and bevacizumab (Avastin) have been used alone or in combination with chemotherapy. Although radiation therapy is occasionally used in patients with colon cancer, it is usually used in combination with chemotherapy for patients with stage III rectal cancer. CRC is considered cured in the absence of a recurrence within the first five years. Five year survival rates associated with CRC are as high as 90% in early stage disease, and 40 60% in late-stage disease. Stage I, II, and III cancers are considered potentially curable. In most cases, stage IV cancer is not curable. Epidemiology In 2010, a total of around 1.58 million individuals were affected by CRC in the seven major markets. It was the leading cause of cancer prevalence among men and second among women in Europe. It was also observed that higher survival rates correlated with higher prevalence. Table 5 illustrates colorectal cancer epidemiology. 30

31 Table 5: Estimated prevalence of CRC across the 7MM, 2010 Country Prevalence (000s) Prevalence (%) Share (%) France Germany Italy Spain UK EU US Japan Total 1, Source: IARC GLOBOCAN 2008; Business Insights analysis Forecast epidemiology According to Business Insights estimates, the 2010 prevalence population of around 1.58 million in the seven major markets is projected to grow modestly through to The US will continue to hold the major share owing to its higher population. In terms of rates of increase, the US and Japan are forecast to witness a modest increase in prevalence of the disease, largely as a result of its having already reached epidemic proportions in those countries. Germany and France remain key regions for growth in prevalence. 31

32 Table 6: Forecast epidemiology of CRC across the 7MM, Country France Prevalence (000s) Prevalence (%) Germany Prevalence (000s) Prevalence (%) Italy Prevalence (000s) Prevalence (%) Spain Prevalence (000s) Prevalence (%) UK Prevalence (000s) Prevalence (%) EU5 Prevalence (000s) Prevalence (%) US Prevalence (000s) Prevalence (%) Japan Prevalence (000s) Prevalence (%) Total Prevalence (000s) 1, , , , , , , Prevalence (%) Source: IARC GLOBOCAN 2008; Business Insights analysis 32

33 Breast cancer Overview Breast cancer is the most common cancer in women and has the largest market in terms of numbers of patients diagnosed. Globally, breast cancer is the most common type of cancer, representing around 10% of all cancer types. The most common site of breast cancer is the milk ducts (more than 75%) followed by lobules. It is also found in men at a very low rate of below 1%. There are several factors that increase the prospect of developing breast cancer. The chances increase with age or with a family history of breast cancer. There is also increased risk with a personal history of cancer in one breast. Recently it has been found that lifestyle also plays an important role in breast cancer, with potential causes including oral contraceptives, late pregnancy, smoking, alcohol, hormone replacement therapies, lack of exercise, being overweight, and breast implants. Figure 2: Types of breast cancers Subtypes Comments Ductal carcinoma in situ (DCIS) Lobular carcinoma in situ (LCIS) Infiltrating ductal carcinoma (ILC) Infiltrating lobular carcinoma (ILC) Inflammatory breast cancer (IBC) Limited to ducts; 80 90% cases Limited to milk glands Starts in ducts; 80% of all invasive breast cancers Starts in milk glands Rubor and calor, 1 3 % of all cancers Source: American Cancer Society Diagnosis, treatment, and management Early detection is always best for the treatment and prevention of malignancy. Breast self-examination is the simplest diagnostic option. Mammograms are strongly recommended for women above 40 years old. Magnetic resonance imaging (MRI) and biopsies are used in later stages. Genetic counseling is another 33

34 technique used to help women with a familial history of breast cancer from breast cancer 1 susceptibility protein (BRCA1) and breast cancer 2 susceptibility protein (BRCA2) mutations. The most common treatment followed currently is surgery, which ranges from lymph node biopsy and simple lumpectomy to mastectomy. In most cases it is followed up with adjuvant radiation therapy, chemotherapy, and hormone therapy. Chemotherapy is based on whether the tumors are positive or negative for human epidermal growth factor receptor 2 (HER2). For HER2-positive tumors, the first-line therapy is typically an aromatase inhibitor. If the tumor does not overexpress a hormone receptor, then the standard therapy is taxane-based chemotherapy. The second and further lines of therapy in HER2-negative breast cancer are often based on a capecitabine-containing regimen. Additionally, Herceptin has long been established as standard of care for HER2-overexpressing metastatic breast cancer (MBC). In the first line it is typically combined with a taxane. In the second line it is often used as a monotherapy. Epidemiology Based on the IARC GLOBOCAN 2008 database, it is estimated that in 2010 over two million people were affected by breast cancer. It is the leading cause of cancer-related deaths among women, yet relative to other cancers it features one of the lowest mortality rates across the seven major markets. 34

35 Table 7: Estimated prevalence of breast cancer across the 7MM, 2010 Country Prevalence (000s) Prevalence (%) Share (%) France Germany Italy Spain UK EU US 1, Japan Total 2, Source: IARC GLOBOCAN 2008; Business Insights analysis Much of the variation among the Western countries that have a high prevalence of breast cancer, and Spain, which has the lowest estimated prevalence, can be attributed to ethnicity and the regional presence of risk factors. Breast cancer typically features lower rates of mortality than the majority of other cancers, which can be attributed to health promotional activities that have led to greater disease awareness and the improved diagnostic capabilities now available in the seven major markets. Forecast epidemiology Prevalence rates in the seven major markets are expected to grow modestly to just over 2.14 million in The modest increase is based on growth-driving trends such as an early age of menarche, women having fewer than three children, and the increasing elderly population 35

36 Table 8: Forecast epidemiology of breast cancer across the 7MM, Country France Prevalence (000s) Prevalence (%) Germany Prevalence (000s) Prevalence (%) Italy Prevalence (000s) Prevalence (%) Spain Prevalence (000s) Prevalence (%) UK Prevalence (000s) Prevalence (%) EU5 Prevalence (000s) Prevalence (%) US Prevalence (000s) 1, , , , , , , Prevalence (%) Japan Prevalence (000s) Prevalence (%) Total Prevalence (000s) 2, , , , , , , Prevalence (%) Source: IARC GLOBOCAN 2008; Business Insights analysis 36

37 Ovarian cancer Overview Ovarian cancer is a malignant tumor affecting the ovaries. It is the second most common type of gynecological malignancy in the world. Ovarian cancer is classified according to the histology of the tumor, and can be grouped into four main categories: Ovarian epithelial carcinoma A carcinoma of the surface cells of the ovary, it accounts for more than 80% of ovarian cancers. Germ cell tumor A carcinoma of the egg-producing cells within the ovary, it constitutes 5% of all ovarian cancers and mostly among young women and girls. Sex cord stromal ovarian carcinoma A carcinoma of the ovarian connective tissue, it accounts for about 8% of ovarian cancers. These are steroid-producing tumors. Rare ovarian tumors that are largely benign in nature An example is Krukenberg cancers, which originate from gastrointestinal cancer and account for an estimated 1% of ovarian cancer cases. Older women are at the highest risk of developing ovarian cancer, with high incidence rates observed in post-menopausal women in the age group of years. Hormonal, environmental, and genetic factors also play important roles in the development of ovarian cancer. Child-bearing status and infertility are important, as is the presence of inherited mutation in one of two genes called BRCA1 and BRCA2, which are associated with ovarian and breast cancer in younger women. Diagnosis, treatment, and management Diagnosis of ovarian cancer is undertaken if the physician observes symptoms such as abdominal bloating followed by vaginal bleeding, chronic pelvic pain, gastrointestinal (GI) symptoms, or urinary tract symptoms. Ovarian cancers are normally detected in the late stages, as their symptoms are mostly non-specific. Typically, diagnosis involves pelvic examination, ultrasound, or a CA 125 blood test (CA 125 is a protein antigen found at high levels in the serum of ovarian cancer patients). To date, no targeted agents have been approved for ovarian cancer therapy. The first-line standard of care is surgery followed by 37

38 carboplatin/paclitaxel chemotherapy. Surgery involves the removal of the affected ovary and the fallopian tube, followed by chemotherapy or radiotherapy. For relapsed disease, if the relapse is more than six months after first-line therapy, patients usually respond to carboplatin/paclitaxel again. However, if patients relapse within six months, these tumors are usually platinum-resistant and new agents must be used. Chemotherapy agents typically used in platinum-resistant patients are Gemzar, topotecan, and etoposide. Epidemiology Ovarian cancer is the second most common gynecological malignancy among women. Among the seven major markets, it has affected around 170,000 women in 2010, with the UK having the highest prevalence among the top five EU countries. Table 9: Estimated prevalence of ovarian cancer across the 7MM, 2010 Country Prevalence (000s) Prevalence (%) Share (%) Germany UK France Italy Spain EU US Japan Total Source: IARC GLOBOCAN 2008; Business Insights analysis Forecast epidemiology The forecast growth of ovarian cancer across the seven major markets is modest. The prevalence of ovarian cancer is set to grow from 170,280 in 2010 to 174,429 in This is governed by several counteracting drivers such as a lower number of childbirths per woman, a higher proportion of elderly people in the population. The US, Germany, and Japan are forecast to register the highest prevalence figures in 2016, which closely follows the current population trends. 38

39 Table 10: Forecast epidemiology of ovarian cancer across the 7MM, Country France Prevalence (000s) Prevalence (%) Germany Prevalence (000s) Prevalence (%) Italy Prevalence (000s) Prevalence (%) Spain Prevalence (000s) Prevalence (%) UK Prevalence (000s) Prevalence (%) EU5 Prevalence (000s) Prevalence (%) US Prevalence (000s) Prevalence (%) Japan Prevalence (000s) Prevalence (%) Total Prevalence (000s) Prevalence (%) Source: IARC GLOBOCAN 2008; Business Insights analysis 39