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Monoclonal Antibodies Market in Breast Cancer to 2019 Strong Uptake of Novel HER-2 Targeted Therapies to Drive Robust Growth

GBI Research Report Guidance

© GBI Research. This is a licensed product and is not to be photocopied GBIHC309MR / Published OCT 2013

GBI Research Report Guidance

The report begins with an executive summary detailing the key points that are driving the global mAbs in breast cancer market.

Chapter two provides an introduction to breast cancer, detailing the etiology, epidemiology, diagnostic techniques, disease staging of the disease and typical prognoses for patients. An analysis of current treatment algorithms and options is also included, with special emphasis on the role of mAbs.

Chapter three offers detailed analysis of the five mAbs currently marketed for this indication – Herceptin, Avastin, Perjeta, Kadcyla and Xgeva. This includes key characteristics of these drugs, including: safety and efficacy, clinical trial outcomes, tolerability, dosing, administration, historical sales, prices and overall competitive strength. These products are also compared in a comprehensive heat map.

Chapter four provides detailed analysis of the pipeline for breast cancer, with particular focus on mAbs, by stage of development, molecule type, program type, mechanism of action and molecular target. It also analyses recent clinical trials in this indication by enrollment, duration and failure rate. Finally, promising late-stage pipeline molecules are analyzed and assessed in terms of their potential competitive strength.

Chapter five supplies market forecasts for mAbs in the breast cancer market, including: epidemiology, treatment usage patterns, pricing and market size for the 2012–2019 period. Eight major markets (US, Canada, Germany, UK, France, Italy, Spain and Japan) are covered and data are presented at a country level with further analysis of key market drivers and barriers.

Chapter six describes the major deals that have taken place in the global mAbs in breast cancer market in recent years. This coverage analyzes: licensing and co-development agreements, segmented by stage of development, year, molecule type, mechanism of action and value. Network graphs for these deals by location of company headquarters are also included.

An appendix is included in chapter seven. This lists key definitions, explanations of abbreviations, details of the methodology and sources used.


Monoclonal Antibodies Market in Breast Cancer to 2019 – Executive Summary

Monoclonal Antibodies Market in Breast Cancer to 2019 – Executive Summary

Breast cancer is a highly common malignancy in women, with an estimated XX new cases in the US occurring in 2013 (Siegel et al., 2013). For the majority of patients diagnosed in the early stages of the disease, survival rates are high, ranging from XX% to almost XX%. However, in patients with metastatic disease, a long-term cure is almost certainly unfeasible. While chemotherapy, surgery and radiation therapy are able to improve outcomes to an extent, monoclonal antibodies (mAb) that are currently available are far more effective and safe than chemotherapy in this regard and afford a superior standard of care in suitable patients.

In the decade following the introduction of the first mAb, Herceptin (trastuzumab) into the breast cancer market in 1998, the drug became a global blockbuster. Despite not being approved for any other indication, the drug achieved sales of $XX billion in 2009. This is due to its relatively strong safety profile and excellent efficacy profile, both in the prevention of recurrence in early breast cancer, and life extension in the metastatic setting.

Avastin was introduced to the market in 2008, but it was found to be ineffective and its marketing approval was revoked in 2011; it was not until 2012 that a clinically effective addition was made to the market for mAbs in breast cancer. This addition, Perjeta (pertuzumab), was approved in the US for the treatment of metastatic breast cancer in combination with Herceptin, providing a further incremental survival benefit in this subset of patients. The approval of Kadcyla (ado-trastuzumab emtansine), a biobetter of Herceptin, in metastatic breast cancer one year later has also advanced the standard of care in this market.

All three of these mAbs are marketed by Roche, and are part of their franchise of drugs that target the Human Epidermal growth factor Receptor-2 (HER-2), which is overexpressed in XX–XX% of patients. Currently, there are no effective mAbs for patients who do not overexpress this protein, creating a strong unmet need in this area, particularly in patients with the metastatic form of the disease.

Of XX pipeline molecules, XX% are mAbs. The late-stage pipeline for breast cancer contains XX Phase III mAbs and XX in Phase II, although only XX of the Phase III candidates is a novel treatment. While many of these pipeline mAbs are targeted to HER-2 overexpressing patients, a significant share of this pipeline segment comprises molecules that are either targeted to a different subpopulation of breast cancer patients, or are useful in the entire patient population. This means that while the large HER-2 negative subpopulation of breast cancer currently represents a very strong opportunity due to a lack of competition from other mAbs, it is likely to become far more competitive in the mid- to-long term due to the entry of targeted therapies into this market segment.

Market for mAbs in Breast Cancer, Global, Pipeline by Stage of Development, 2006–2012

Discovery

Preclinical

IND/CTA-filed

Phase I

Phase II

Phase III

Pre-registration

Pipeline by Stage of Development

Total: XX

Plus an additional XXpipeline products at undisclosed stages of development

Source: GBI Research Proprietary Pipeline Products Database

In the decade following the introduction of […] Herceptin (trastuzumab) into the breast cancer market, […] the drug became a global blockbuster


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Table of Contents

1 Table of Contents

1 Table of Contents ................................................................................................................................. 5 1.1 List of Tables ............................................................................................................................. 7 1.2 List of Figures............................................................................................................................ 8

2 Monoclonal Antibodies in Breast Cancer to 2019 – Introduction ........................................................... 9 2.1 Symptoms ................................................................................................................................ 9 2.2 Etiology .................................................................................................................................... 9 2.3 Epidemiology ...........................................................................................................................10 2.4 Pathophysiology ......................................................................................................................10 2.5 Diagnosis .................................................................................................................................11 2.6 Prognosis and Disease Staging ..................................................................................................11

2.6.1 Classification ....................................................................................................................13 2.7 Treatment Options ..................................................................................................................13

2.7.1 Surgery and Radiation Therapy .........................................................................................13 2.7.2 Chemotherapy .................................................................................................................14 2.7.3 Hormonal Therapies .........................................................................................................15 2.7.4 Targeted Therapies ..........................................................................................................15 2.7.5 Resistance to Pharmacological Therapies ..........................................................................16 2.7.6 Treatment Guidelines .......................................................................................................17 2.7.7 Measuring the Effectiveness of Treatment ........................................................................19

3 Marketed Products .............................................................................................................................20 3.1 Herceptin (Trastuzumab) – Hoffmann La Roche ........................................................................20 3.2 Avastin (Bevacizumab) – Hoffmann La Roche ............................................................................23 3.3 Kadcyla (Trastuzumab Emtansine) – Hoffmann La Roche...........................................................25 3.4 Perjeta (Pertuzumab) – Hoffmann La Roche .............................................................................26 3.5 Xgeva (denosumab) – Amgen ...................................................................................................27 3.6 Heat Map for Marketed Products .............................................................................................28 3.7 Conclusion ...............................................................................................................................31

4 Pipeline for Breast Cancer Monoclonal Antibody Therapeutics .............................................................32 4.1 Overall Pipeline........................................................................................................................33 4.2 Mechanisms of Action ..............................................................................................................35 4.3 Clinical Trials ............................................................................................................................37

4.3.1 Attrition Rate ...................................................................................................................38 4.3.2 Clinical Trial Size...............................................................................................................39 4.3.3 Duration ..........................................................................................................................41 4.3.4 Clinical Trial End-points ....................................................................................................43

4.4 Promising Drug Candidates in the Pipeline ................................................................................45 4.4.1 CDX-011 (glembatumumab vedotin) – Celldex Therapeutics ..............................................45 4.4.2 Metmab (onartuzumab) – Hoffman La Roche ....................................................................45 4.4.3 Hu3S193 – Recepta Biopharma .........................................................................................45 4.4.4 MM-121 – Merrimack Pharmaceuticals ............................................................................46 4.4.5 IMC-18F1 (Icrucumab) – Eli Lilly ........................................................................................46 4.4.6 Rexomun (Ertumaxomab) – Fresenius Biotech ...................................................................46 4.4.7 Medi-573 (Dusigitumab) – Medimmune ............................................................................46 4.4.8 MK-0646 (Dalotuzumab) – Merck and Co ..........................................................................47 4.4.9 LY3012217 (Cixutumumab) - Eli Lilly .................................................................................47

4.5 Conclusion ...............................................................................................................................47 5 Market Forecast to 2019 .....................................................................................................................49

5.1 Global ......................................................................................................................................49 5.1.1 Treatment Usage Patterns................................................................................................49 5.1.2 Market Size ......................................................................................................................50


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Table of Contents

5.2 US ...........................................................................................................................................51 5.2.1 Treatment Usage Patterns................................................................................................51 5.2.2 Market Size ......................................................................................................................52

5.3 Canada ....................................................................................................................................53 5.3.1 Treatment Usage Patterns................................................................................................53 5.3.2 Market Size ......................................................................................................................54

5.4 Europe.....................................................................................................................................55 5.4.1 Treatment Usage Patterns................................................................................................55 5.4.2 Annual Cost of Therapy ....................................................................................................56 5.4.3 Market Size ......................................................................................................................57

5.5 Japan .......................................................................................................................................59 5.5.1 Treatment Usage Patterns................................................................................................59 5.5.2 Market Size ......................................................................................................................60

5.6 Drivers and Barriers .................................................................................................................61 5.6.1 Drivers .............................................................................................................................61 5.6.2 Barriers ............................................................................................................................61

6 Deals and Strategic Consolidations ......................................................................................................62 6.1 R&D Licensing Agreements ......................................................................................................62

6.1.1 Key Licensing Deals ..........................................................................................................65 6.2 Co-development Agreements ...................................................................................................67

6.2.1 Key Deals .........................................................................................................................67 7 Appendix ............................................................................................................................................70

7.1 References ..............................................................................................................................70 7.2 References for Heat Map .........................................................................................................75 7.3 All Pipeline Products, by Phase .................................................................................................76

7.3.1 Discovery .........................................................................................................................76 7.3.2 Preclinical ........................................................................................................................77 7.3.3 IND/CTA Filed and Phase I ................................................................................................78 7.3.4 Phase II ............................................................................................................................79 7.3.5 Phase III and Pre-Registration ...........................................................................................80

7.4 Market Definitions ...................................................................................................................81 7.5 Abbreviations ..........................................................................................................................81 7.6 Tabular Forecast Data ..............................................................................................................82

7.6.1 Global ..............................................................................................................................82 7.6.2 US....................................................................................................................................82 7.6.3 Canada ............................................................................................................................82 7.6.4 UK ...................................................................................................................................83 7.6.5 France .............................................................................................................................83 7.6.6 Germany ..........................................................................................................................83 7.6.7 Italy .................................................................................................................................83 7.6.8 Spain ...............................................................................................................................84 7.6.9 Japan ...............................................................................................................................84

7.7 Research Methodology ............................................................................................................85 7.7.1 Coverage .........................................................................................................................85 7.7.2 Secondary Research .........................................................................................................85

7.8 Therapeutic Landscape ............................................................................................................86 7.9 Epidemiology-Based Forecasting ..............................................................................................86 7.10 Market Size by Geography .......................................................................................................87 7.11 Geographical Landscape ..........................................................................................................88 7.12 Pipeline Analysis ......................................................................................................................88 7.13 Competitive Landscape ............................................................................................................88

7.13.1 Expert Panel Validation ....................................................................................................88


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Table of Contents

7.14 Contact Us ...............................................................................................................................88 7.15 Disclaimer................................................................................................................................88

1.1 List of Tables

Table 1: Market for mAbs in Breast Cancer, Global, TNM Staging, 2010–2013 .......................................11 Table 2: Market for mAbs in Breast Cancer, US, Disease Stage at Diagnosis and Five-year Relative Survival

(%), 2013 ................................................................................................................................12 Table 3: Market for mAbs in Breast Cancer, References for Heat Map (Figure 6) ....................................75 Table 4: Breast Cancer Therapeutics, Global, All Pipeline Products (Discovery), 2013 .............................76 Table 5: Breast Cancer Therapeutics, Global, All Pipeline Products (Preclinical), 2013 ............................77 Table 6: Breast Cancer Therapeutics, Global, All Pipeline Products (Phase I and IND/CTA filed), 2013 .....78 Table 7: Breast Cancer Therapeutics, Global, All Pipeline Products (Phase II), 2013 ................................79 Table 8: Breast Cancer Therapeutics, Global, All Pipeline Products (Phase III and Pre-Registration), 2013

...............................................................................................................................................80 Table 9: Market for mAbs in Breast Cancer, Global, Forecast Data, 2012–2019 ......................................82 Table 10: Market for mAbs in Breast Cancer, US, Forecast Data, 2012–2019............................................82 Table 11: Market for mAbs in Breast Cancer, Canada, Forecast Data, 2012–2019 ....................................82 Table 12: Market for mAbs in Breast Cancer, UK, Forecast Data, 2012–2019 ...........................................83 Table 13: Market for mAbs in Breast Cancer, France, Forecast Data, 2012–2019 .....................................83 Table 14: Market for mAbs in Breast Cancer, Germany, Forecast Data, 2012–2019 ..................................83 Table 15: Market for mAbs in Breast Cancer, Italy, Forecast Data, 2012–2019 .........................................83 Table 16: Market for mAbs in Breast Cancer, Spain, Forecast Data, 2012–2019 .......................................84 Table 17: Market for mAbs in Breast Cancer, Japan, Forecast Data, 2012–2019 .......................................84


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1.2 List of Figures

Figure 1 Market for mAbs in Breast Cancer, Global, Treatment Algorithm for Cancer Diagnosed at Stages I to III ........................................................................................................................................17

Figure 2: Market for mAbs in Breast Cancer, Global, Treatment Algorithm for Cancer Diagnosed at Stage IV ...........................................................................................................................................18

Figure 3: Market for mAbs in Breast Cancer, Global, Sales of Herceptin ($bn), 1999–2012 ......................21 Figure 4: Market for mAbs in Breast Cancer, Global, Sales of Avastin ($bn), 2004–2012 ..........................24 Figure 5: Market for mAbs in Breast Cancer, Global, Aggregate Sales of Xgeva and Prolia ($m), 2010–2012

...............................................................................................................................................27 Figure 6: Market for mAbs in Breast Cancer, Global, Heat Map (Marketed Products) ..............................30 Figure 7: Market for mAbs in Breast Cancer, Global, Pipeline by Stage of Development, 2013 .................33 Figure 8: Market for mAbs in Breast Cancer, Global, mAbs by Mechanism of Action, 2013 ......................35 Figure 9: Market for mAbs in Breast Cancer, Global, mAbs by Mechanism of Action (Growth Factor

Inhibitors), 2013 .....................................................................................................................36 Figure 10: Market for mAbs in Breast Cancer, Global, mAbs by Molecular Target (Targeted Cytotoxic),

2013 .......................................................................................................................................37 Figure 11: Market for mAbs in Breast Cancer, Global, Pipeline by Stage of Development, 2013 .................38 Figure 12: Market for mAbs in Breast Cancer, Global, Pipeline by Stage of Development, 2013 .................39 Figure 13: Market for mAbs in Breast Cancer, Global, Clinical Trial Size, 2013 ...........................................40 Figure 14: Market for mAbs in Breast Cancer, Global, Clinical Trial Duration, 2006–2013 ..........................41 Figure 15: Market for mAbs in Breast Cancer, Global, Clinical Trial Durations, 2006–2013 .........................42 Figure 16: Market for mAbs in Breast Cancer, Global, Clinical Trial Endpoints for Phases II and III, 2006–

2012 .......................................................................................................................................43 Figure 17: Market for mAbs in Breast Cancer, Global, Clinical Trial Endpoints for Phases II and III per

Product, 2006–2012 ................................................................................................................44 Figure 18: Market for mAbs in Breast Cancer, Global, Treatment Usage Patterns, 2012–2019 ...................49 Figure 19: Market for mAbs in Breast Cancer, Global, Market Size ($bn), 2012–2019 ................................50 Figure 20: Market for mAbs in Breast Cancer, US, Treatment Patterns, 2012–2019 ...................................51 Figure 21: Market for mAbs in Breast Cancer, US, Market Size ($bn), 2012–2019 ......................................52 Figure 22: Market for mAbs in Breast Cancer, Canada, Treatment Usage Patterns, 2012–2019 .................53 Figure 23: Market for mAbs in Breast Cancer, Canada, Market Size ($m), 2012–2019 ...............................54 Figure 24: Market for mAbs in Breast Cancer, Top Five European Markets, Treatment Usage Patterns,

2012–2019 .............................................................................................................................55 Figure 25: Market for mAbs in Breast Cancer, Top Five European Markets, Annual Cost of Therapy ($),

2012–2019 .............................................................................................................................56 Figure 26: Market for mAbs in Breast Cancer, Top Five European Markets, Market Size ($m), 2012–2019 58 Figure 27: Market for mAbs in Breast Cancer, Japan, Treatment Usage Patterns, 2012–2019 ....................59 Figure 28: Market for mAbs in Breast Cancer, Japan, Market Size ($m), 2012–2019 ..................................60 Figure 29: Market for mAbs in Breast Cancer, Global, Licensing Deals (All Molecule Types), 2006–2012 (A)

...............................................................................................................................................62 Figure 30: Market for mAbs in Breast Cancer, Global, Licensing Deals (All Molecule Types), 2006–2012 (B)

...............................................................................................................................................63 Figure 31: Market for mAbs in Breast Cancer, Global, Licensing Deals (All Molecule Types), 2006–2012 (C)

...............................................................................................................................................64 Figure 32: Market for mAbs in Breast Cancer, Global, Co-development Deals (All Molecule Types) by

Partner Country, 2006–2012 ...................................................................................................67 Figure 33: Market for mAbs in Breast Cancer, Global, Co-development Deals by Molecule Type, 2006–2012

...............................................................................................................................................68 Figure 34: GBI Research Market Forecasting Model .................................................................................87


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Monoclonal Antibodies Market in Breast Cancer to 2019 – Introduction

2 Monoclonal Antibodies Market in Breast Cancer to 2019 – Introduction

Breast cancer is a disease caused by the uncontrollable proliferation of cells in the breast. Although it is most frequently diagnosed in women, in rare cases it can also occur in males (GLOBOCAN, 2008). The term ‘breast cancer’ covers a variety of neoplasms that have distinct molecular, histological, and genomic properties. As such, the treatment course varies between different patients.

2.1 Symptoms

Breast cancers most commonly present as lumps, rashes, or thickening around the breast tissue. In the early stages, they are usually asymptomatic, with a solid lump being the most common initial symptom (Vogel, 2008).

Metastatic breast cancer can present as a variety of non-specific symptoms, such as unexplained weight loss, fever, chills, and bone pain.

2.2 Etiology

The most important risk factor for breast cancer, by far, is gender. Each year, almost all cases of breast cancer occur in females, with just a small fraction occurring in males. This is due to higher lifetime estrogen exposure in females in comparison to males as the majority of risk factors for breast cancer are influenced by estrogen exposure (Ademuyiwa et al., 2011).Male and female breast cancers are generally similar in terms of survival rates (American Cancer Society, 2013a).

Apart from gender, risk of breast cancer is most heavily linked to age, with XX% of new cases occurring in patients over the age of XX (American Cancer Society, 2012). The reasons for the linkage of cancer risk to aging are unclear, but are likely caused in part by tissue changes, cellular senescence, and the accumulation of random somatic mutations throughout one’s lifetime. Ethnicity also plays a role, with a higher incidence rate amongst the US population being reported in Caucasians (XX per XX), and a substantially lower rate observed in Asian Americans (XX per XX) (DeSantis et al., 2011). This is likely to be due, in part, to lifestyle factors such as diet and the use of oral contraceptives; Asian women who migrate to the US have a higher incidence of breast cancer than their counterparts native to Japan (Saika and Sobue, 2009; Cancer Research UK, 2012a).

Although the underlying genetic makeup of Asian subpopulations is likely to influence the risk of breast cancer, lifestyle and dietary factors are currently thought to have a stronger effect, and have been driving increasing incidence of breast cancer in Asian women since the 1980s (Liu et al., 2011). A lower incidence rate relative to Caucasians is also observed in African-American women (XX per XX) in the US, However, individuals within this ethnic group are at a higher risk of worse prognosis than Caucasians and Asian Americans (a five-year cause-specific survival rate of XX% observed for African Americans versus XX% for Caucasians and XX% for Asian Americans) (DeSantis et al., 2011). The underlying factors of this racial disparity are poorly understood but are thought to reflect both genetic differences and disparities in the screening for and management of breast cancer between different ethnic groups (Ademuyiwa et al., 2011). Having a family history of breast cancer is also considered to be a risk factor, albeit weak compared to the three previously described traits. Typically, a family history of breast cancer only presents a substantially increased risk of contracting the disease under specific conditions; for example, the risk in daughters of female breast cancer patients only increases if the mother was under XX at the time of incidence (Cancer Research UK, 2012a). Having several relatives who were previously diagnosed with breast cancer, or any close male relatives, can also generally be considered to be a risk factor.

Regarding heritable risk factors, there are a number of specific mutations that are well-defined in terms of their roles in the pathogenesis of breast cancer. Approximately XX–XX% of all breast cancers are inherited (Holstege et al., 2009).

The most common of these are the BRCA1 and BRCA2 genes, which account for approximately XX% of breast cancer cases in the US, and approximately XX% of all inherited breast cancers (Donovan and Livingston, 2010; Holstege et al., 2009). These are known as tumor suppressor genes, and are important components of the DNA repair and cell cycle control processes. As such, inheriting a dysfunctional copy of the BRCA1 gene has been shown to increase the lifetime risk of contracting breast cancer to ~XX%, while for BRCA2 this figure is XX%. Faulty BRCA1 and BRCA2 genes are also risk factors for a number of other cancers, such as ovarian, prostate, and pancreatic cancer.

Apart from gender, risk of breast cancer is most heavily linked to age, with XX% of new cases occurring in patients over the age of XX


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Marketed Products

3.6 Heat Map for Marketed Products

When the clinical trials conducted for mAbs in breast cancer are broadly compared to one another, Herceptin appears to have the greatest impact on survival times amongst metastatic breast cancer patients.

Herceptin was the only drug to have been studied in Phase III for its use in early-stage breast cancer patients, for which data is publicly available. It is consistently able to improve overall and disease-free survival to a moderate extent compared to placebo, in addition to survival free of distant metastatic recurrences. However, the incidence of cardiac safety events was highest in Herceptin, compared to the other three drugs. Both Herceptin and Kadcyla carry boxed warnings for this risk of cardiotoxicity, in addition to a risk of severe infusion reactions with Herceptin and a risk of fatal hepatotoxicity with Kadcyla.

This is a major weakness of Herceptin, meaning that if its competitor products Kadcyla and Perjeta are non-inferior to it in terms of efficacy and do not induce any new serious safety issues, they will have a strong competitive advantage over Herceptin. However, due to the serious nature of oncology indications, a product which is even moderately inferior to the current standard in terms of efficacy would be unlikely to successfully compete, even if the safety profile was superior.

Avastin was the weakest performer, and was only able to bring about a substantial improvement in PFS. Its impact on disease-free and OS was marginal in most studies, which is the primary reason for its commercial failure and the withdrawal of its marketing approval in the US.

Kadcyla is indicated for patients who have already been treated with Herceptin, while Perjeta is used exclusively in combination with Herceptin. The fact that Perjeta greatly improves survival compared to Herceptin alone, while Kadcyla has a similarly potent effect on progression-free and OS in patients who have already been treated with Herceptin and chemotherapy, indicate that these drugs have a strong therapeutic and commercial potential. With the exception of Avastin, which is a poorer drug, the marketed mAbs for breast cancer occupy distinct spaces in the treatment of breast cancer, and as such one cannot be deemed superior to another. However, pooled clinical trial results indicate that they are all highly effective in their own niches, although an unmet need still remains, particularly in patients with metastatic breast cancer, for which the prognosis is still generally poor.

A meta-analysis conducted by the Cochrane Collaboration concluded that Herceptin confers a significant benefit to both overall and disease-free survival, but also increases the risk of cardiovascular complications such as congestive heart failure (Moja et al., 2012). On the other hand, another Cochrane Collaboration meta-analysis regarding Avastin concluded it to confer no significant benefit to OS, and that its overall benefit in cancer was “modest at best” (Wagner et al., 2012). A different meta-analysis for Avastin confirms this, finding that while it is able to reduce the tumor mass and improve PFS it does not confer a significant benefit in terms of OS (Rossari et al., 2012)

Marketed Products

© GBI Research. This is a licensed product and is not to be photocopied GBIHC309MR / Published OCT 2013 Page 30

Figure 6: Market for mAbs in Breast Cancer, Global, Heat Map (Marketed Products)

Drug name Generic name Phase Study design #### #### #### #### #### #### #### #### #### #### #### #### #### #### #### #### #### #### #### #### #### ####

####

(Trial Drug + Chemotherapy) vs. (Chemotherapy + Placebo)

56 3387 1 24 8.40 - 7.80 0.90 1.11 - 1.09 1.01 - - 1.49 28.83 - - - Early-Stage 3 ####

####


52 4045 2 48 12.00 - - 7.40 1.16 - - 1.09 - - - 27.00 - - - Early-Stage 1 ####

####


9 231 3 60 3.20 - 8.50 5.20 1.04 - 1.11 1.09 - - - 0.53 - - -

Early-Stage High Risk/Locally Advanced

1 ####

####


52 528 4 47 3.00 - 4.7 -1 1.04 - 1.06 0.99 - - - 2.53 - - - Locally Advanced 3 ####

####


52 235 5 36 15.00 - - 8.00 1.27 - - 1.10 - - - 1.06 - - - Locally Advanced 3 ####

####


- 469 6 15 - 3.90 - 12.20 - 2.56 - 1.21 4.8 2.8 - 5.00 1.62 1.83 1.16 Metastatic 1 ####

####(Trial Drug + Docetaxel) vs. (Docetaxel + Placebo)

18 198 7 35 - - - - - - - - 8.5 5.6 - 1.90 - 2.05 - Metastatic 1 ####

####(Trial Drug) plus (capecitabine) vs. (capecitabine)

16 462 8 16 - - - - - - - - 0.60 0.69 - 4.69 1.09 0.47 1.21 Metastatic 3 ####

####(Trial Drug) plus (paclitaxel) vs. (paclitaxel)

234 722 9 24 -0.70 9.14 - 5.00 0.99 2.49 - 1.10 1.50 5.90 - 2.67 3.21 - - Metastatic 2 ####

- 7.76 - 5.00 - 1.32 - 1.07 -1.10 0.90 1.18 - - - -HER-2 Negative, Metastatic

3 ####

- 4.87 - 8.00 - 1.39 - 1.11 -1.70 1.90 1.22 - - - -HER-2 Negative, Metastatic

3 ####

(Trial Drug) plus (capecitabine) vs. (placebo) plus (capecitabine)

208 615 - 7.95 - 6.60 - 1.47 - 1.09 - - 1.29 - - - -

HER-2 Negative, Metastatic, or locally recurrent

(Trial Drug) plus (taxane) vs. (placebo) plus (taxane)

208 622 - 5.74 - -2.50 - 1.33 - 0.97 - - 1.49 - - - -

HER-2 Negative, Metastatic, or locally recurrent

(Trial Drug) plus (chemotherapy) vs. (placebo) plus (chemotherapy)

156 684 12 12 - 4.29 - 3.30 - 1.29 - 1.05 1.60 2.10 1.39 - - - -HER-2 Negative, Metastatic

2-3 ####

Kadcyla ado-trastuzumab emtansine

(Trial Drug) plus (lapatinib) plus (capecitabine) vs. (placebo) plus (lapatinib) plus (capecitabine)

130 991 13 12 - 9.72 - 6.80 - 1.91 - 1.09 5.80 3.20 0.72 - - - -Locally Advanced or metastatic

3 ####

Perjeta pertuzumab

(Trial Drug) plus (trastuzumab) plus (docetaxel) vs. (placebo) plus (trastuzumab) plus (docetaxel)

152 808 14 20 - 10.30 - 4.83 - 2.00 - 1.14 - 6.10 1.24 1.8 - - - Metastatic 3 ####

####

####

Other traits

3 ####

#### ####

10 12

#### 11 12

736

Avastin bevacizumab

####

Trial Drug) plus (docetaxel) vs. (placebo) plus (docetaxel)

27

Safety Parameters (In proportion with comparator)Drug profiles for marketed products Follow-

upResponse at follow-up (percentage of patients, points versus comparator)

Response at follow-up (percentage of patients, ratio with comparator)

Life extension (months benefit versus comparator)

Source: Sources are displayed in the appendix

Pipeline for Breast Cancer Monoclonal Antibody Therapeutics

© GBI Research. This is a licensed product and is not to be photocopied GBIHC309MR / Published OCT 2013 Page 36

Of the growth factor inhibitors, a high proportion (XX%) is made up of biosimilars.. The pipeline for growth factor antagonist-biosimilars includes three products at Phase I, and four at Phase III.

Figure 9: Market for mAbs in Breast Cancer, Global, mAbs by Mechanism of Action (Growth Factor Inhibitors), 2013

HER-1

HER-2

HER-2, HER-3

HER-3

EGFR Family Antagonists by Molecular Target

Total: XX

C

EGFR family

Insulin-like growth factor

VEGF

Growth Factor Antagonists by Type

Total: XX

B

Discovery Preclinical Phase I Phase II Phase III

Num

ber o

f pro

duct

s

Growth Factor Antagonists by Phase and Type

VEGF Multiple Insulin-like growth factor EGFR family

A

Source: GBI Research Pipeline Products Database

However, the earlier stages such as Phase I and the preclinical stage comprise far fewer antibodies of this type. Here, targeted cytotoxic drugs make up a larger proportion of the products for which the mechanism of action has been disclosed. Additionally, products that function by other, more disparate mechanisms of action occupy a marginally larger faction than at later stages of development.

Most of the growth factor blockers, which are the most prevalent type of mAb in the mid-to-late stage pipeline, act on a member of the EGFR family. Some XX% of all growth factor blockers belong to this class and of these, XX% specifically target the HER-2 receptor. Therefore, approximately XX% of the pipeline is made up of HER-2 inhibitors. As the only approved products that do not target HER-2 do not account for a significant share of this market, this trend indicates a potential diversification of mAb-based approaches to breast cancer treatment in the future.

With the undisclosed products taken into account, this equates to just a quarter of the pipeline for mAbs and around XX% of the overall pipeline for breast cancer which is made up of mAbs that act on the HER-2 receptor. In addition, an even smaller proportion acts on VEGF or VEGFR. These are particularly small proportions, given the success of both Herceptin and Avastin. Overall, despite the current dominance of the breast cancer market by mAbs, it appears that other approaches such as small-molecule products may attain a much greater share in future.

Most of the growth factor blockers, which are the most prevalent type of mAb in the mid-to-late stage pipeline, act on a member of the EGFR family


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Deals and Strategic Consolidations

Figure 30: Market for mAbs in Breast Cancer, Global, Licensing Deals (All Molecule Types), 2006–2012 (B)

StronglyConnected

WeaklyConnected

Source: GBI Research Proprietary Deals Database

Node sizes, arrow sizes and edge thicknesses correspond to the volume of deals occurring, with larger nodes, larger arrows and

thicker edges indicating a higher volume of deals.

The overall level of licensing activity in breast cancer is relatively high, with a large sum of money exchanged for licensing deals in recent years. However, the level of licensing activity for mAbs appears to be relatively low compared to small molecules in this indication; while some XX% of the pipeline for breast cancer is composed of mAbs, only XX% of all licensing deals taking place from 2006–2012 concerned products belonging to this molecule type. Additionally, there were no deals with a disclosed value, while for small molecules the aggregate value was $XX billion.

The overall level of licensing activity in breast cancer is relatively high, with a large sum of money exchanged for licensing deals in recent years


Page 64

Deals and Strategic Consolidations

Figure 31: Market for mAbs in Breast Cancer, Global, Licensing Deals (All Molecule Types), 2006–2012 (C)

Growth factor antagonist (HER-2) Growth factor antagonist (VEGFR-2) Growth factor antagonist (PDGFR) Other

Num

ber o

f dea

ls

Deals by Mechanism of ActionD

Discovery Phase I Phase II Phase III Filed Marketed

Num

ber o

f dea

ls

Number of deals by Phase and molecule type

Vaccine Small molecule Protein Peptide mAb

B

Upf

ront

dis

close

d de

al v

alue

($m

)

Tota

l dis

clos

ed d

eal v

alue

($m

)

Licensing Deals by Phase and ValueDeal Value ($m) Upfront Payment ($m)A

mAb Peptide Protein Small molecule

Vaccine

Mea

n de

al v

alue

($m

)

Aggr

egat

e de

al v

alue

($m

)

Aggregate and Mean Deal Value by Molecule Type

Aggregate deal value ($m) Mean deal value ($m)

n=0 n=1 n=1

n=16

n=3

Mea

n di

sclo

sed

deal

val

ue ($

m)

Num

ber o

f dea

ls

Number of undisclosed deals Number of d isclosed dealsMean d isclosed deal value

C

Source: GBI Research Proprietary Deals Database


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Appendix

7 Appendix

7.1 References

Abdullah L and Chow E (2013). Mechanisms of chemoresistance in cancer stem cells. Clinical and Translational Medicine; 2 (1): 3.

Ademuyiwa F et al. (2011). Breast Cancer Racial Disparities: Unanswered Questions. Cancer Research; 71 (3): 640—644.

Aebi S et al. (2011). Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology; 22 (s6): 12–24.

American Cancer Society (2012). Breast cancer facts and figures 2011–2012. American Cancer Society. Available from: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-030975.pdf

American Cancer Society (2013a). What are the key statistics about breast cancer in men? Available from: http://www.cancer.org/cancer/breastcancerinmen/detailedguide/breast-cancer-in-men-key-statistics [Accessed on June 3, 2013].

American Cancer Society (2013b). How is breast cancer diagnosed? Available from: http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-diagnosis [Accessed on June 3, 2013].

American Cancer Society (2013c). How is breast cancer treated? Available from: http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-treating-general-info [Accessed on June 4, 2013].

American Joint Committee on Cancer (2010). Cancer Staging Poster Series. Available from: http://www.cancerstaging.org/staging/ [Accessed on June 4, 2013].

Bell N (2003). RANK ligand and the regulation of skeletal remodeling. The Journal of Clinical Investigation; 111 (8): 1,120–1,122.

Bonine-Summers A et al. (2007). Epidermal Growth Factor Receptor Plays a Significant Role in Hepatocyte Growth Factor Mediated Biological Responses in Mammary Epithelial Cells. Cancer Biology and Therapy; 6 (4): epub.

Booth C and Eisenhauer E (2012). Progression-Free Survival: Meaningful or Simply Measurable? Journal of Clinical Oncology; 30 (10): 1,030–1,033.

Breast Cancer Care (2012). Cancer size and grade. Available from: http://www.breastcancercare.org.uk/breast-cancer-information/about-breast-cancer/diagnosis/cancer-size-grade [Accessed on June 4, 2013].

Bria E, et al. (2008). Trastuzumab cardiotoxicity: biological hypotheses and clinical open issues. Expert Opinion on Biological Therapy; 8 (12): 1,963–1,971.

Burris H et al. (2009). A Phase (Ph) I/II Study of CR011-VcMMAE, an Antibody-Drug Conjugate, in Patients (Pts) with Locally Advanced or Metastatic Breast Cancer (MBC). Cancer Research; 69 (24): 6,096.

Burstein H et al. (2012). Choosing the Best Trastuzumab-Based Adjuvant Chemotherapy Regimen: Should We Abandon Anthracyclines? Journal of Clinical Oncology; 30 (18): 2,179–2,182.

Cameron D et al. (2012). Primary results of BEATRICE, a randomized phase III trial evaluating adjuvant bevacizumab-containing therapy in triple-negative breast cancer. Cancer Research; 72 (24): S3.

Cancer Research UK (2012a). Definite breast cancer risks. Available from: http://www.cancerresearchuk.org/cancer-help/type/breast-cancer/about/risks/definite-breast-cancer-risks [Accessed on June 3, 2013].


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Appendix

7.2 References for Heat Map

Table 3: Market for mAbs in Breast Cancer, References for Heat Map (Figure 6)

Number Reference

1 Piccart-Gebhart M et al. (2005). Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer. The New England Journal of Medicine; 353(16): 1659-1672.

2 Perez E et al. (2011). Four-Year Follow-Up of Trastuzumab Plus Adjuvant Chemotherapy for Operable Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Joint Analysis of Data From NCCTG N9831 and NSABP B-31. Journal of Clinical Oncology; 29 (25): 3366-3373.

3 Jonesuu H et al. (2009). Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. Journal of Clinical Oncology; 27(34): 5685-5692.

4 Spielmann M et al. (2009). Trastuzumab for Patients with Axillary-Node-Positive Breast Cancer: Results of the FNCLCC-PACS-04 Trial. Journal of Clinical Oncology; 27(36), 6129-6134.

5

Gianni L et al. (2010). Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial ith a parallel HER2-negative cohort. Lancet; 375: 377-384.

6 Slamon D et al. (2001). Use of Chemotherapy Plus a Monoclonal Antibody Against HER2 for Metastatic Breast Cancer that Overexpresses HER2. The New England Journal of Medicine; 344 (11): 783-792.

7

Marty M et al. (2005). Randomized Phase II trial of the Efficacy and Safety of Trastuzumab Combined With Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Administered As First-Line Treatment: The M77001 Study Group, Journal of Clinical Oncology; 23(19): 4265-4274.

8 Miller K et al. (2005). Randomized Phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. Journal of Clinical Oncology; 23(4): 792-799.

9 Miller K et al. (2007). Paclitaxel plus Bevacizumab versus Paclitaxel Alone for Metastatic Breast Cancer. The New England Journal of Medicine; 357: 2666-2676.

10 Miles D et al. (2010). Phase III Study of Bevacizumab Plus Docetaxel Compared With Placebo Plus Docetaxel for the First-Line Treatment of Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer. Journal of Clinical Oncology; 28(20): 3239-3247.

11

Robert N et al. 2011, RIBBON-1: Randomized, Double-Blind, Placebo-Controlled, Phase III Trial of Chemotherapy With or Without Bevacizumab for First-Line Treatment of Human Epidermal Growth Factor Receptor 2–Negative, Locally Recurrent or Metastatic Breast Cancer. Journal of Clinical Oncology; 29(10): 1252-1260.

12

Brufsky A, et al. (2011). RIBBON-2: A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy for Second-Line Treatment of Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer. Journal of Clinical Oncology; 29(32): 4286-4293.

13 Verma S et al. (2012), Trastuzumab Emtansine for HER-2 Positive advanced breast cancer. The New England Journal of Medicine; 367(19): 1783-1791.

14 Baselga J et al. (2012), Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer. The New England Journal of Medicine; 366(2): 109-119.

Source: GBI Research


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Appendix

7.3 All Pipeline Products, by Phase

7.3.1 Discovery

Table 4: Breast Cancer Therapeutics, Global, All Pipeline Products (Discovery), 2013

Product Name Company Molecule Type Mechanism of Action Stage of Development



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Appendix

7.3.2 Preclinical

Table 5: Breast Cancer Therapeutics, Global, All Pipeline Products (Preclinical), 2013

Product Name Company Molecule Type

Mechanism of Action Stage of Development



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Appendix

7.3.3 IND/CTA Filed and Phase I

Table 6: Breast Cancer Therapeutics, Global, All Pipeline Products (Phase I and IND/CTA filed), 2013




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Appendix

7.3.4 Phase II

Table 7: Breast Cancer Therapeutics, Global, All Pipeline Products (Phase II), 2013




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Appendix

7.3.5 Phase III and Pre-Registration

Table 8: Breast Cancer Therapeutics, Global, All Pipeline Products (Phase III and Pre-Registration), 2013




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Appendix

7.4 Market Definitions

The global mAbs in Breast Cancer Market includes the top eight markets; consisting of the US, the UK, Germany, France, Spain, Italy, Japan and Canada.

The top five European countries are the UK, Germany, France, Spain and Italy

Prevalence population: The prevalence population is the estimated number of people at any given point of time who are affected by breast cancer.

7.5 Abbreviations

ACoT: Annual Cost of Therapy

ACT: Adriamycin, Cyclophosphamide and Taxol

ADT: Androgen Deprivation Therapy

API: Active Pharmaceutical Ingredient

BBB: Blood-Brain Barrier

CD3: Cluster of Differentiation 3

CT: X-ray Computed Tomography

DFS: Disease-Free Survival

ER: Estrogen Receptor

FC Gamma: Fragment Crystallizable Gamma

FDA: Food and Drug Administration

GPNMB: Transmembrane Glycoprotein Neuromedin B-like protein

HDAC: Histone Deacetylase

HER: Human Epidermal Growth Factor Receptor

HER-2: Human Epidermal Growth Factor Receptor

HGPIN: High Grade Prostatic Intraepithelial Neoplasia

IGF: Insulin-like Growth Factor

IGF-1: Insulin-like Growth Factor 1

IGF-2: Insulin-like Growth Factor 2

OS: Overall Survival

LVEF: Left Ventricular Ejection Fraction

mAb: monoclonal Antibody

MAPK-ERK: Mitogen-Activated Protein Kinase- Extracellular signaling-related Kinases

MRI: Magnetic Resonance Imaging

NICE: National Institute for Clinical Excellence

OS: Overall Survival

PARP: Poly-Adenosine Diphosphate Ribose Polymerase

PFS: Progression-Free Survival

PR: Progesterone Receptor

RANK-L: Receptor activator of nuclear factor Kappa-B ligand

RECIST: Response Evaluation Criteria in Solid Tumors

SARM: Selective Androgen Receptor Modulator


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Appendix

SERM: Selective Estrogen Receptor Modulator

TNBC: Triple-Negative Breast Cancer

TNM: Tumor size, Node involvement, Metastasis staging

TS: Thymidylate Synthase

TTP: Time To Progression

VEGF: Vascular Endothelial Growth Factor

VEGF-R: Vascular Endothelial Growth Factor-Receptor

7.6 Tabular Forecast Data

7.6.1 Global

Table 9: Market for mAbs in Breast Cancer, Global, Forecast Data, 2012–2019

Year 2012 2013 2014 2015 2016 2017 2018 2019

Prevalence population (‘000)

Treatment population (‘000)

Minimum revenues ($m)

Projected revenues ($m)

Maximum revenues ($m)


7.6.2 US

Table 10: Market for mAbs in Breast Cancer, US, Forecast Data, 2012–2019

Year 2012 2013 2014 2015 2016 2017 2018 2019







7.6.3 Canada

Table 11: Market for mAbs in Breast Cancer, Canada, Forecast Data, 2012–2019

Year 2012 2013 2014 2015 2016 2017 2018 2019








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Appendix

7.6.4 UK

Table 12: Market for mAbs in Breast Cancer, UK, Forecast Data, 2012–2019

Year 2012 2013 2014 2015 2016 2017 2018 2019







7.6.5 France

Table 13: Market for mAbs in Breast Cancer, France, Forecast Data, 2012–2019

Year 2012 2013 2014 2015 2016 2017 2018 2019







7.6.6 Germany

Table 14: Market for mAbs in Breast Cancer, Germany, Forecast Data, 2012–2019

Year 2012 2013 2014 2015 2016 2017 2018 2019







7.6.7 Italy

Table 15: Market for mAbs in Breast Cancer, Italy, Forecast Data, 2012–2019

Year 2012 2013 2014 2015 2016 2017 2018 2019








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Appendix

7.6.8 Spain

Table 16: Market for mAbs in Breast Cancer, Spain, Forecast Data, 2012–2019

Year 2012 2013 2014 2015 2016 2017 2018 2019







7.6.9 Japan

Table 17: Market for mAbs in Breast Cancer, Japan, Forecast Data, 2012–2019

Year 2012 2013 2014 2015 2016 2017 2018 2019








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Appendix

7.7 Research Methodology

GBI Research’s dedicated research and analysis teams consist of experienced professionals with marketing, market research and consulting backgrounds in the pharmaceutical industry as well as advanced statistical expertise.

GBI Research adheres to the codes of practice of the Market Research Society (www.mrs.org.uk) and the Strategic and Competitive Intelligence Professionals (www.scip.org).

All GBI Research databases are continuously updated and revised.

7.7.1 Coverage

The objective of updating GBI Research coverage is to ensure that it represents the most up-to-date vision of the industry possible.

Changes to the industry taxonomy are built on the basis of extensive research of company, association and competitor sources.

Company coverage is based on three key factors: market capitalization, revenues and media attention/innovation/market potential.

An exhaustive search of 56 member exchanges is conducted and companies are prioritized on the basis of their market capitalization.

The estimated revenues of all major companies, including private and governmental, are gathered and used to prioritize coverage.

Companies which are making the news, or which are of particular interest due to their innovative approach, are prioritized.

GBI Research aims to cover all major news events and deals in the pharmaceutical industry, updated on a daily basis.

The coverage is further streamlined and strengthened with additional inputs from GBI Research’s expert panel (see below).

7.7.2 Secondary Research

The research process begins with exhaustive secondary research on internal and external sources being carried out to source qualitative and quantitative information relating to each market.

The secondary research sources that are typically referred to include, but are not limited to:

Company websites, annual reports, financial reports, broker reports, investor presentations and US Securities and Exchanges Commission (SEC) filings

Industry trade journals, scientific journals and other technical literature

Internal and external proprietary databases

Relevant patent and regulatory databases

National government documents, statistical databases and market reports;

Procedure registries

News articles, press releases and web-casts specific to the companies operating in the market


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Appendix

7.8 Therapeutic Landscape

Revenues for each indication, geography-wise is arrived at by utilizing the GBI Research market forecasting model. The global revenue for each indication is the sum value of revenues of all eight regions.

The annual cost of treatment for each indication is arrived at by considering the cost of the drugs, dosage of the drugs and the duration of the therapy.

The generic share of the market for each indication is obtained by calculating the prescription share for generic drugs and the respective cost of treatment.

The treatment usage pattern which includes quantitative data on the diseased population, treatment-seeking population, diagnosed population and treated population for an indication, is arrived at by referring to various sources as mentioned below.

GBI Research uses the epidemiology-based treatment flow model to forecast market size for therapeutic indications.

7.9 Epidemiology-Based Forecasting

The forecasting model used at GBI Research makes use of epidemiology data gathered from research publications and primary interviews with physicians to represent the treatment flow patterns for individual diseases and therapies. The market for any disease segment is directly proportional to the volume of units sold and the price per unit.

Sales = Volume of units sold X Price per unit

The volume of units sold is calculated on the average dosage regimen for that disease, duration of treatment and number of patients who are prescribed drug treatment (prescription population). Prescription population is calculated as the percentage of population diagnosed with a disease (diagnosis population). The diagnosis population is the population diagnosed with a disease expressed as a percentage of the population that is seeking treatment (the treatment-seeking population). The prevalence of a disease (diseased population) is the percentage of the total population that suffers from a disease/condition.

Data on treatment-seeking rates and diagnosis and prescription rates, if unavailable from research publications, are gathered from interviews with physicians and are used to estimate the patient volumes for the disease under consideration. Therapy uptake and compliance data are fitted in the forecasting model to account for patient switching and compliance behavior.

To account for differences in patient affordability of drugs across various geographies, macroeconomic data such as inflation and GDP and healthcare indicators such as healthcare spending, insurance coverage and average income per individual are used.

The annual cost of treatment is calculated using product purchase frequency and the average price of the therapy. Product purchase frequency is calculated from the dosage data available for the therapies and drug prices are gathered from public sources. The source for the price of drugs are RxUSA, ZenRx, the UK Prescription Cost Analysis, the British National Formulary and data from the Japan Pharmaceutical Information Center (JAPIC).

The epidemiology-based forecasting model uses a bottom-up methodology and it makes use of estimations in the absence of data from research publications. Such estimations may result in a final market value which is different from the actual value. To correct this ‘gap’ the forecasting model uses ‘triangulation’ with the help of base year sales data (from company annual reports, internal and external databases) and sales estimations.

Analogous Forecasting Methodology

Analogous forecasting methodology is used to account for the introduction of new products, patent expiries of branded products and subsequent introduction of generics. Historic data for new product launches and generics penetration are used to arrive at robust forecasts. Increase or decrease of prevalence rates, treatment seeking rate, diagnosis rate and prescription rate are fitted into the forecasting model to estimate market growth rate.


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Appendix

The proprietary model enables GBI Research to account for the impact of individual drivers and restraints in the growth of the market. The year of impact and the extent of impact are quantified in the forecasting model to provide close-to-accurate data sets.

7.10 Market Size by Geography

The treatment usage pattern and ACoT in each country has been factored in while deriving the individual country market size.

Forecasting Model for Therapeutic Areas

Figure 34: GBI Research Market Forecasting Model

D is ease P opu la ti onGener a l Po pu la tio n 743,535 ,048

Q ualify ing c ond ition 1 (Age /S ex/O c c upa tion etc )Q ualify ing c ond ition 2 (Age /S ex/O c c upa tion etc )

Preva l ence t issu e va lve disease 0 .2% 1,784 ,484 Q ualify ing c ond ition (c om plic at ion , s everity)D IS EA SE D P OPU LAT IO N 1,784 ,484

T r eatm en t Flow P attern sT reatm ent S eek i ng R at e (Sy m ptom s/ Dis A wareness) 89% 1,588 ,191 Diagn osis Rat e ( C lin ica l and D iagn ostic Test s ) 75% 1,191 ,143

Prescr iption R ate ( Ph ysic ian P ercep t io n, Tr eatm ent E ffectiv e n ess)Tis s ue V a lve 70% 833,800 O ther T rea tm ents fo r Va lve (Sur g /M ed/N one) -

F ulfi llm en tA vailab i lit y NAW illingness to U s e (Pa tient Perc eptions) NAR eady to U se (S urgery el ig ib ility , R eus e e tc ) NA

Affo rd abil it y a t PriceH E as % of G D P s pendA verage Inc om e (per ind ividua l)P at ien t O ut-o f -poc ke t Budge t (A nnua l)

Budget a lloc a tion to one-t ime s urgeryBudget a lloc a tion to o ther h ealth needs

A verage Pay or C overageP at ien t L iab il ityTarget Pr ic e ( @ 20% pa t liab )A SP for C os t o f T herapy

T O TA L P AT IEN T V OLU M E SPro du ct P urch ase Fr equ en c y 1

T OT A L UN IT VO LU MES

Pr ic in g per Un it 18 ,000$ Inf lationP rice D ec reas e due to c om pet it ion

M ar ket Va lu e

G B I R esear ch M ar ket Siz in g M o del


The above figure represents a typical forecasting model followed in GBI Research. As discussed previously, the model is built on the treatment flow patterns. The model starts with the general population, then diseased population as a percentage of the general population and then follows the treatment seeking population as a percentage of the diseased population and diagnosed population as a percentage of the treatment seeking population. Finally, the total volume of units sold is calculated by multiplying the treated population by the average dosage per year per patient.


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Appendix

7.11 Geographical Landscape

This report series GBI Research covers the following major developed markets: the US, Canada, the top five countries in Europe – the UK, Germany, France, Spain, Italy – and Japan. The total market size for each country is provided which is the sum value of the market sizes of all the indications for that particular country.

7.12 Pipeline Analysis

This section provides a list of molecules at various stages in the pipeline for various indications. The list is sourced from internal database and validated for the accuracy of phase and mechanism of action at ClinicalTrials.gov and company websites. The section also includes a list of promising molecules which is narrowed down based on the results of the clinical trials at various stages and the novelty of mechanism of action. The latest press releases issued by the company and news reports are also the source of information for the status of the molecule in the pipeline.

7.13 Competitive Landscape

GBI Research aims to cover all major licensing deals and co-development deals related to the market. This section is sourced from the companies’ websites, company annual reports and internal databases

7.13.1 Expert Panel Validation

GBI Research uses a panel of experts to cross verify its databases and forecasts.

GBI Research expert panel comprises marketing managers, product specialists, international sales managers from pharmaceutical companies; academics from research universities and key opinion leaders from hospitals.

Historic data and forecasts are relayed to GBI Research’s expert panel for feedback and are adjusted in accordance with their feedback.

7.15 Disclaimer

All Rights Reserved.

No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher, GBI Research.

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