Colorectal Cancer Therapeutics in Major Developed Markets ... · Colorectal Cancer Therapeutics in...

THERAPY ANALYSIS

Colorectal Cancer Therapeutics in Major Developed Markets to 2020 - Increased

Uptake of High Priced Drugs to Offset the Impact of Generics

Report Code: GBIHC352MR Published: January 2015

www.gbiresearch.com

© GBI Research. This is a licensed product and is not to be photocopied

GBIHC352MR / Published JAN 2015

GBI Research Report Guidance

The report begins with an executive summary detailing the key points driving the CRC market in eight major markets: the US, the UK, France, Germany, Spain, Italy, Japan and Canada.

Chapter two provides an introduction to CRC, detailing etiology, epidemiology, diagnostic techniques, disease staging and typical prognoses for patients. An analysis of current treatment algorithms and options is also included.

Chapter three offers detailed analysis of the drugs currently marketed for this indication: 5-FU, Xeloda, Camptosar, Eloxatin, Avastin, Zaltrap, Vectibix, Stivarga and Erbitux. This includes key characteristics, covering 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 CRC according to 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 the CRC market, including epidemiology, treatment use patterns, pricing, and market size, for the forecast period from 2013 to 2020. The eight major markets 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 CRC 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.


GBIHC352MR / Published JAN 2015

Executive Summary

Moderate growth expected for the Colorectal Cancer (CRC) market

The value of the Colorectal Cancer (CRC) therapeutics market across eight major countries – the US, the UK, France, Germany, Spain, Italy, Japan and Canada – amounted to $XX billion in 2013, and is expected to increase moderately at a Compound Annual Growth Rate (CAGR) of XX% to $XX billion in 2020. The US had the largest market value in 2013, with $XX billion, equivalent to a global share of XX%, followed by Japan with $XX billion or XX% and Germany with $XXm or XX%. Spain had the lowest market share and value of the leading eight with $XXm or XX%.

Of the markets covered in the report, Japan is expected to register growth at the fastest pace, with a CAGR of XX%. However, this moderate growth will be stymied by the expected uptake of low-cost biosimilar versions of bevacizumab and cetuximab, due to the expected patent expiration of Avastin and Erbitux in the latter half of the forecast period. A number of generic versions of capecitabine are also expected to be launched, which will be affecting the market. However, the impact of patent expirations will be offset by the launch of premium priced emerging therapies.

Stivarga (regorafenib) is expected to be one of the biggest drivers of growth in the CRC market, due primarily to its expected line extension as a maintenance treatment in the first-line metastatic setting as a maintenance treatment for patients with resected liver metastases. The launch of Lonsurf (TAS-102), which was approved in Japan in 2014, in the third- and fourth-line settings will further increase the pharmacological treatment rates in these lines, which would give patients a more tolerable alternative to Stivarga. The efficacy shown by TAS-102 is similar to that of regorafenib, but prescribers view it as having a more tolerable safety profile.

The launch of Zaltrap (ziv-aflibercept) by Sanofi/Regeneron has given patients an alternative angiogenesis inhibitor in the second-line setting, which will be prescribed primarily to patients who have progressed quickly on bevacizumab in the first-line setting. Eli Lilly’s Cyramza (ramucirumab), which will target patients in a similar setting as Zaltrap, is also expected to be launched in 2015. The uptake of Cyramza in this setting will be limited, predominantly because of its premium pricing over Zaltrap.

Colorectal Cancer Therapeutics, Global, Market Size ($bn), 2013–2020

2013 2014 2015 2016 2017 2018 2019 2020

Mar

ket s

ize

($bn

)

Low variance Medium variance High variance Projected

Source: GBI Research, Proprietary Pipeline Products Database; GBI Research, Proprietary Marketed Products Database

Stivarga is expected to be one of the biggest drivers of growth in the CRC market.


GBIHC352MR / Published JAN 2015 Page 5

1 Table of Contents

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

2 Introduction ........................................................................................................................................................9 2.1 Colorectal Cancer ................................................................................................................................9 2.2 Symptoms ..............................................................................................................................................9 2.3 Epidemiology ........................................................................................................................................9 2.4 Pathophysiology ................................................................................................................................. 10

2.4.1 Histology ..................................................................................................................................... 10 2.4.2 Genetic Basis .............................................................................................................................. 10 2.4.3 Etiology of Colorectal Cancer .................................................................................................. 11

2.5 Diagnosis ............................................................................................................................................. 12 2.5.1 Digital Rectal Examination ....................................................................................................... 12 2.5.2 Fecal Occult Blood Test ........................................................................................................... 12 2.5.3 Flexible Sigmoidoscopy ........................................................................................................... 12 2.5.4 Colonoscopy............................................................................................................................... 13 2.5.5 Virtual Colonoscopy .................................................................................................................. 13 2.5.6 Double Contrast Barium Enema ............................................................................................. 14

2.6 Prognosis and Disease Staging....................................................................................................... 14 2.7 Treatment Options ............................................................................................................................. 16

2.7.1 Surgery and Radiation Therapy .............................................................................................. 16 2.7.2 Chemotherapy ........................................................................................................................... 16 2.7.3 Targeted Therapies ................................................................................................................... 17 2.7.4 Resistance to Pharmacological Therapies............................................................................ 17 2.7.5 Treatment Guidelines ............................................................................................................... 18

3 Marketed Products ........................................................................................................................................ 22 3.1 Key Marketed Products .................................................................................................................... 22

3.1.1 Immunotherapies ...................................................................................................................... 22 3.1.2 Targeted Therapies .................................................................................................................. 26 3.1.3 Hyperthermic Intraperitoneal Chemotherapy ...................................................................... 31

3.2 Heat Map for Marketed Products .................................................................................................... 31 4 Pipeline Analysis ............................................................................................................................................ 34

4.1 Overall Pipeline.................................................................................................................................. 34 4.2 Pipeline Analysis by Molecule Type .............................................................................................. 35 4.3 Pipeline Analysis by Mechanism of Action ................................................................................... 36 4.4 Clinical Trials ...................................................................................................................................... 38 4.5 Failure Rate ........................................................................................................................................ 38 4.6 Clinical Trial Size ............................................................................................................................... 40 4.7 Duration............................................................................................................................................... 42 4.8 Promising Drug Candidates in Pipeline ........................................................................................ 44

4.8.1 Lonsurf (TAS-102 (tipiracil + trifluridine)) – Taiho Pharmaceutical ................................... 44 4.8.2 Cyramza – ramucirumab – Eli Lilly and Company .............................................................. 44 4.8.3 TS-1/Teysuno (tegafur + gimeracil + oteracil) – Taiho Pharmaceutical ........................... 45 4.8.4 CPP-1X (eflornithine hydrochloride) + sulindac – Cancer Prevention Pharmaceuticals

...................................................................................................................................................... 46 4.8.5 MelCancerVac – DanDrit Biotech ..........................................................................................47 4.8.6 Xilonix – XBiotech .................................................................................................................... 48 4.8.7 Nintedanib – Boehringer Ingelheim...................................................................................... 49

5 Market Forecast to 2020 ............................................................................................................................. 50 5.1 Global Market ..................................................................................................................................... 50



5.1.1 Treatment Use Patterns .......................................................................................................... 50 5.1.2 Market Size ................................................................................................................................ 50

5.2 North America .................................................................................................................................... 52 5.2.1 Treatment Use Patterns .......................................................................................................... 52 5.2.2 Annual Cost of Therapy ........................................................................................................... 52 5.2.3 Market Size ................................................................................................................................ 53

5.3 Top Five European Markets ............................................................................................................ 54 5.3.1 Treatment Use Patterns .......................................................................................................... 54 5.3.2 Annual Cost of Therapy ........................................................................................................... 56 5.3.3 Market Size ................................................................................................................................ 57

5.4 Japan ................................................................................................................................................... 58 5.4.1 Treatment Use Patterns .......................................................................................................... 58 5.4.2 Annual Cost of Therapy ........................................................................................................... 59 5.4.3 Market Size ................................................................................................................................ 60

5.5 Drivers and Barriers for the Colorectal Cancer Therapeutics in Major Developed Markets to 2020................................................................................................................................................. 61

5.5.1 Drivers .......................................................................................................................................... 61 5.5.2 Barriers ....................................................................................................................................... 62

6 Deals and Strategic Consolidations ........................................................................................................... 64 6.1 Licensing Agreements ..................................................................................................................... 64

6.1.1 Major Licensing Deals ............................................................................................................. 67 6.2 Co-development Agreements ........................................................................................................ 68

6.2.1 Major Co-development Agreements .................................................................................... 70 7 Appendix .......................................................................................................................................................... 71

7.1 All Pipeline Drugs by Phase ............................................................................................................. 71 7.1.1 Discovery..................................................................................................................................... 71 7.1.2 Preclinical ................................................................................................................................... 72 7.1.3 IND/CTA-Filed ............................................................................................................................73 7.1.4 Phase I .........................................................................................................................................73 7.1.5 Phase II ........................................................................................................................................74 7.1.6 Phase III ...................................................................................................................................... 75

7.2 Market Forecasts to 2020 ............................................................................................................... 75 7.2.1 Global .......................................................................................................................................... 75 7.2.2 US ................................................................................................................................................ 75 7.2.3 Canada ....................................................................................................................................... 76 7.2.4 UK ................................................................................................................................................ 76 7.2.5 France ......................................................................................................................................... 76 7.2.6 Germany ...................................................................................................................................... 77 7.2.7 Italy ............................................................................................................................................... 77 7.2.8 Spain ............................................................................................................................................ 77 7.2.9 Japan............................................................................................................................................ 77

7.3 Market Definitions ............................................................................................................................. 78 7.4 Abbreviations ..................................................................................................................................... 78 7.5 References .......................................................................................................................................... 81 7.6 References for Heat Map ................................................................................................................. 86 7.7 Research Methodology .................................................................................................................... 87

7.7.1 Coverage .................................................................................................................................... 87 7.7.2 Secondary Research ................................................................................................................ 87 7.7.3 Primary Research ...................................................................................................................... 88 7.7.4 Therapeutic Landscape ........................................................................................................... 88 7.7.5 Geographical Landscape ......................................................................................................... 91 7.7.6 Pipeline Analysis ........................................................................................................................ 91



7.8 Expert Panel Validation ..................................................................................................................... 91 7.9 Contact Us ........................................................................................................................................... 91 7.10 Disclaimer ............................................................................................................................................ 91

1.1 List of Tables

Table 1 Colorectal Cancer Therapeutics, Global, TNM Staging, 2013 .............................................15 Table 2 Surgical Options for Colorectal Cancer................................................................................16 Table 3 Colorectal Cancer Therapeutics, Global, All Pipeline Products (Discovery), 2014 ..............71 Table 4 Colorectal Cancer Therapeutics, Global, All Pipeline Products (Preclinical), 2014 .............72 Table 5 Colorectal Cancer Therapeutics, Global, All Pipeline Products (IND/CTA-Filed), 2014 ......73 Table 6 Colorectal Cancer Therapeutics, Global, All Pipeline Products (Phase I), 2014 ..................73 Table 7 Colorectal Cancer Therapeutics, Global, All Pipeline Products (Phase II), 2014 .................74 Table 8 Colorectal Cancer Therapeutics, Global, All Pipeline Products (Phase III), 2014 ................75 Table 9: Colorectal Cancer Therapeutics, Global, Forecast Data, 2013–2020.................................75 Table 10: Colorectal Cancer Therapeutics, US, Forecast Data, 2013–2020 ......................................75 Table 11: Colorectal Cancer Therapeutics, Canada, Forecast Data, 2013–2020...............................76 Table 12: Colorectal Cancer Therapeutics, UK, Forecast Data, 2013–2020 ......................................76 Table 13: Colorectal Cancer Therapeutics, France, Forecast Data, 2013–2020 ................................76 Table 14: Colorectal Cancer Therapeutics, Germany, Forecast Data, 2013–2020 ............................77 Table 15: Colorectal Cancer Therapeutics, Italy, Forecast Data, 2013–2020.....................................77 Table 16: Colorectal Cancer Therapeutics, Spain, Forecast Data, 2013–2020 ..................................77 Table 17: Colorectal Cancer Therapeutics, Japan, Forecast Data, 2013–2020 .................................77 Table 18: Colorectal Cancer Market, References for Heat Map ..........................................................86

1.2 List of Figures

Figure 1: Colorectal Cancer Therapeutics, Global, European Society for Medical Oncology Treatment Guidelines (Colorectal Cancer at Stage I to III) ...................................................19

Figure 2: Colorectal Cancer Therapeutics, Global, European Society for Medical Oncology Treatment Guidelines (Colorectal Cancer at Stage IV) ........................................................20

Figure 3: Colorectal Cancer Therapeutics, Global, Heat Map (Marketed Products) ..........................33 Figure 4: Colorectal Cancer Therapeutics, Global, Pipeline by Stage of Development and Program

Type, 2014 .............................................................................................................................34 Figure 5: Colorectal Cancer Therapeutics, Global, Pipeline by Molecule Type and Stage of

Development, 2014 ...............................................................................................................35 Figure 6: Colorectal Cancer Therapeutics, Global, Pipeline by Mechanism of Action and Stage of

Development, 2014 ...............................................................................................................37 Figure 7: Colorectal Cancer Therapeutics, Global, Clinical Trial Failure Rate (%), 2014 .....................39 Figure 8: Colorectal Cancer Therapeutics, Global, Clinical Trial Size, 2014 .......................................41 Figure 9: Colorectal Cancer Therapeutics, Global, Clinical Trial Duration (months), 2014 .................43 Figure 10: Colorectal Cancer Therapeutics, Global, Treatment Use Patterns (‘000) and Market Size

($bn), 2013–2020 .................................................................................................................51 Figure 11: Colorectal Cancer Therapeutics, US and Canada, Treatment Use Patterns (‘000), 2013–

2020......................................................................................................................................52 Figure 12: Colorectal Cancer Therapeutics, US and Canada, Annual Cost of Therapy ($), 2013–2020

...............................................................................................................................................53 Figure 13: Colorectal Cancer Therapeutics, US and Canada, Market Size ($m), 2013–2020 .............54 Figure 14: Colorectal Cancer Therapeutics, Top Five European Markets, Treatment Use Patterns

(‘000), 2013–2020 ................................................................................................................55 Figure 15: Colorectal Cancer Therapeutics, Top Five European Markets, Annual Cost of Therapy ($),

2013–2020 ...........................................................................................................................56 Figure 16: Colorectal Cancer Therapeutics, Top Five European Markets, Market Size ($m), 2013–

2020......................................................................................................................................58 Figure 17: Colorectal Cancer Therapeutics, Japan, Treatment Use Pattern, 2013–2020 ...................59 Figure 18: Colorectal Cancer Therapeutics, Japan, Annual Cost of Therapy, 2013–2020..................60



Figure 19: Colorectal Cancer Therapeutics, Japan, Market Size ($m), 2013–2020 .............................61 Figure 20: Colorectal Cancer Therapeutics, Global, Licensing Deals by Geography, 2006–2014 .....65 Figure 21: Colorectal Cancer Therapeutics, Global, Licensing Deals by Phase, Value, Mechanism of

Action, 2006–2014 ...............................................................................................................66 Figure 22: Colorectal Cancer Market, Global, Co-development Deals by Geography and by Value,

2006–2014 ...........................................................................................................................69 Figure 23: GBI Research Market Forecasting Model ............................................................................90



2 Introduction

This report contains estimations for 2013 and forecasts until 2020 for Colorectal Cancer (CRC) therapeutics in eight major markets: the US, the UK, France, Germany, Spain, Italy, Japan and Canada. The five-year prevalence is based on annual incidence over five years and takes into account the five-year survival rate. This produces a figure that reflects the number of surviving patients who were diagnosed with CRC in the previous five years and are therefore more likely to undergo pharmacological treatment for the disease than those diagnosed XX or more years earlier. The five-year prevalence population of CRC in these markets was estimated at XX in 2013, which is expected to increase at a moderate Compound Annual Growth Rate (CAGR) of XX% to XX in 2020. The treatment population for CRC in these markets amounted to an estimated XX in 2013 and is expected to grow at a CAGR of XX% to reach XX in 2020.

2.1 Colorectal Cancer

CRC is the third-most commonly diagnosed cancer and the fourth leading cause of mortality (Haggar and Boushey, 2009). In most developed nations, CRC mortality decreased between 1990 and 2008, attributed to improved early diagnosis and the enactment of national screening programs, aimed at higher-risk parts of the population (generally those over XX years old). In developing nations, as diets become increasingly westernized, incidence is increasing, and national screening programs are still largely nascent.

2.2 Symptoms

CRC sometimes arises without any symptoms or can take XX to XX years to develop, and many symptoms are not apparent until the latter stages of the tumor process. For this reason, regular screening is vital for the detection of tumors in the early stages before advanced progression, when it is more curable, in order to improve patient survival and reduce the cost of CRC treatment.

In spite of this, many cases of CRC are only diagnosed when the patient undergoes emergency admission into hospital, due to complicating symptoms of the disease.

Typical symptoms of CRC, as assessed by the primary care physician, are blood in stool, constipation and diarrhea lasting more than several days, and abdominal discomfort. When physical symptoms are assessed, the patient is then typically referred to secondary care, where a colonoscopy can be administered.

2.3 Epidemiology

The incidence of CRC is far higher than for the other cancers of the Gastrointestinal (GI) tract. An estimated XX of XX cancer incident cases in 2008 were CRC, equivalent to XX% of all cancers (WHO, 2012). Esophageal, gastric, liver and pancreatic cancers accounted for far smaller percentages of the total incident cancer population; there are more patients with CRC than with all of these types of cancer combined.

The five-year prevalence population for CRC in major developed markets amounted to an estimated XX in 2013, which is expected to increase at a moderate CAGR of XX% to XX in 2020. This five-year prevalence is based on annual incidence over five years and takes into account five-year survival rate. This produces a figure that reflects the number of surviving patients diagnosed with CRC over the previous five years, who are more likely to undergo pharmacological treatment for the disease than those diagnosed XX or more years earlier.

The treatment population for CRC in the eight markets covered in this report amounted to an estimated XX in 2013 and is expected to register modest growth to reach XX in 2020 at a CAGR of XX%. Despite the high frequency of the disease, its incidence has been steadily decreasing in the US since the 1980s. Elsewhere, the incidence of CRC has been increasing steadily (Jemal et al., 2011).

CRC incidence is higher in the US and Europe than in Japan due to differences in dietary composition, although incidence in Japan is rapidly increasing due to the westernization of the Japanese diet, which has been ongoing since the 1970s (Kuriki and Tajima, 2006; Jemal et al., 2010). Most cases are diagnosed before distant metastasis has occurred, due to the frequent presentation of early-stage symptoms.

CRC is the third-most commonly diagnosed cancer and the fourth leading cause of mortality.



3 Marketed Products

3.1 Key Marketed Products

3.1.1 Immunotherapies

3.1.1.1 5-Fluorouracil

5-FU is a pyrimidine analog and acts as an antimetabolite and antineoplastic agent. It is formulated as a solution for injection for the Intravenous (IV) route of administration. 5-FU may be used alone or in combination with other medications for its palliative action in the management of common malignancies such as colon cancer and breast cancer. 5-FU interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. 5-FU can also be incorporated into RNA in place of Uridine Triphosphate (UTP), producing a fraudulent RNA. The drug is available in XXmg, XXmg, XXmg, XXmg and XXmg strength.

3.1.1.2 Xeloda (Capecitabine) – F. Hoffmann-La Roche

Xeloda (capecitabine) is a fluoropyrimidine carbamate with anti-neoplastic activity. The drug is formulated in the form of tablet for oral administration. It is enzymatically converted to 5-FU in the tumor, where it inhibits DNA synthesis and slows the growth of tumor tissue. Xeloda is used as a single agent for the adjuvant treatment of Dukes’ C colon cancer after surgery and as a first-line treatment of metastatic colorectal carcinoma when treatment with fluoropyrimidine therapy alone is preferred. Xeloda is used for the treatment of metastatic breast cancer in combination with docetaxel, after failure of prior anthracycline-containing chemotherapy. The drug is also used as a monotherapy in the treatment of metastatic breast cancer that is not improved after the treatment with other medicines such as paclitaxel and anthracycline-containing medicine such as doxorubicin. Xeloda is also indicated for the first-line treatment of advanced gastric cancer in combination with a platinum-based regimen.



3.1.2 Targeted Therapies

3.1.2.1 Avastin (bevacizumab) – F. Hoffmann-La Roche

Avastin is a VEGF-A humanized inhibitor mAb, which is approved for the treatment of metastatic CRC across all eight major markets and is marketed by Roche. The drug is also marketed for the treatment of breast cancer, although its efficacy is far weaker in that indication. Avastin is also indicated for the treatment of kidney and Non-Small-Cell Lung Cancer (NSCLC).



4 Pipeline Analysis

4.1 Overall Pipeline

The CRC pipeline is highly robust, with potential drug candidates across various phases of clinical development. With nearly XX active pipeline molecules, the majority of the investigational drug candidates are being evaluated for the treatment of CRC in advanced stages, either as first-line or second-line therapies. The current investigational pipeline candidates include new combination therapies, targeted therapies and promising immunotherapies, as well as chemotherapy drug candidates. As well as these active progressing pipeline molecules, the pipeline also includes nearly XX molecules that are either inactive or discontinued.

As displayed in the following figure, from XX active progressing pipeline molecules, XX (XX%) are in the Phase II stage of development, XX (XX%) are in the Preclinical stage of development, XX (XX%) are in Phase I, and XX (XX%) are in Phase III. As well as these, a substantial number of active drug candidates are in the discovery stage. As shown in panel B, most of the pipeline drugs are novel, and a few are either generic or products that have already been marketed for other indications.

Figure 4: Colorectal Cancer Therapeutics, Global, Pipeline by Stage of Development and Program Type, 2014

A) Colorectal cancer pipeline by stage of development

B) Colorectal cancer pipeline by program type

Phase I Phase II Phase III

Generic Novel Repositioned

Discovery

Preclinical

Phase I

Phase II

Phase III

IND/CTA-filed

Source: GBI Research, Proprietary Pipeline Products Database

CTA: Clinical Trial Application; IND: Investigational New Drug

With nearly XX active pipeline molecules, the majority of the investigational drug candidates are being evaluated for the treatment of CRC in advanced stages, either as first-line or second-line therapies.



4.4 Clinical Trials

The risk of developing a new chemical entity for the pharmaceutical market is well-documented, and the failure rate of pipeline oncology products appears to be rising in Phase II and III (Lacombe and Liu, 2013). This, in turn, has driven up the average cost of bringing a pharmaceutical product onto the market (Dickson, 2009). With companies therefore seeking to maximize the profitability of their pipeline portfolios, efficient risk management and the selection of only the most promising compounds has become an essential task for pharmaceutical companies.

Additionally, the cost of running clinical trials is high, with the result that clinical pipeline product failures are highly expensive. As the cost of clinical trials is partly driven by the number of patients enrolled, median and mean clinical trial enrollment is a key measure of the relative clinical trial costs for different molecule types.

4.5 Failure Rate

Analysis of CRC clinical trials since 2006 reveals a high failure rate of XX% across all stages of clinical development. Attrition rates of molecules in individual stages of development were XX%, XX% and XX% for Phase I, Phase II and Phase III trials, respectively. The overall failure rates for drugs across the entire industry at each individual phase are estimated at XX% for Phase I, XX% for Phase II and XX% for Phase III (Adams et al., 2010).

Analysis of CRC clinical trials since 2006 reveals a high failure rate of XX% across all stages of clinical development



Figure 7: Colorectal Cancer Therapeutics, Global, Clinical Trial Failure Rate (%), 2014

Phase I

Phase II

Phase III

mAbs Small molecule Overall

Phase I

Phase II

Phase III

Specific receptor agonist/antagonist Specific enzyme inhibitors Overall

Overall Small molecule mAbs

Failu

re ra

te (%

)

Source: GBI Research, Proprietary Clinical Trials Database

mAbs: Monoclonal antibody



5 Market Forecast to 2020

5.1 Global Market

5.1.1 Treatment Use Patterns

The five-year prevalence population of CRC in the eight major markets of the US, the UK, France, Germany, Spain, Italy, Japan and Canada amounted to XX in 2013, which is expected to increase at a moderate CAGR of XX% to XX in 2020. Five-year prevalence is based on annual incidence over five years and takes into account the five-year survival rate. This produces a figure that reflects the number of surviving patients who have been diagnosed with CRC within the last five years and are therefore more likely to undergo pharmacological treatment for the disease than those diagnosed XX or more years earlier. The treatment population for CRC in the eight major markets amounted to XX in 2013 and is expected to register modest growth at a CAGR of XX% to XX in 2020.

5.1.2 Market Size

The value of the CRC therapeutics market in the eight major markets – the US, the UK, France, Germany, Spain, Italy, Japan and Canada – amounted to $XX billion in 2013, and is expected to increase moderately at a CAGR of XX% to $XX billion in 2020, driven by the uptake of a host of new pipeline agents. Of the countries covered in this study, the US represented the largest component of the CRC market in 2013, with a value of $XX billion, or a XX% market share, followed by Japan with $XX billion or XX%, and Germany with $XXm or XX%. Spain had the lowest market share and value of the leading eight at XX% and $XXm.

The five-year prevalence population of CRC in the eight major markets of the US, the UK, France, Germany, Spain, Italy, Japan and Canada amounted to XX in 2013, which is expected to increase at a moderate CAGR of XX% to XX in 2020.



Figure 10: Colorectal Cancer Therapeutics, Global, Treatment Use Patterns (‘000) and Market Size ($bn), 2013–2020

2013 2014 2015 2016 2017 2018 2019 2020

Pat

ient

s ('0

00)

A) Treatment use patterns

Five-year prevalence population ('000) Treatment population ('000)

2013 2014 2015 2016 2017 2018 2019 2020

Mar

ket s

ize

($bn

)

B) Revenue

Low variance Medium variance High variance Projected




6 Deals and Strategic Consolidations

6.1 Licensing Agreements

A total of XX licensing deals for drugs indicated for CRC were identified from 2006 to 2014, of which 11 had a disclosed deal value, comprising an aggregate deal value of $XX billion. The vast majority of these deals were out-licensed by companies headquartered in the US with the deals being mostly concentrated in South Korea, Japan and Australia in the APAC region.

Almost all deals for which the molecule type of the drug is known concern small molecules, reflecting dominance in the developmental pipeline. The mechanism of action for drugs involved in licensing deals is mostly unknown, but with a slightly higher number of deals concerning cytotoxic agents, growth factor inhibitors and protein kinase inhibitors.

A total of XX licensing deals for drugs indicated for CRC were identified from 2006 to 2014, of which XX had a disclosed deal value, comprising an aggregate deal value of $XX billion.



Figure 21: Colorectal Cancer Therapeutics, Global, Licensing Deals by Phase, Value, Mechanism of Action, 2006–2014

Pre

clin

ical

Pha

se I

Pha

se II

Pha

se II

I

Mar

kete

d

Und

iscl

osed

Num

ber o

f dea

lsTo

tal d

iscl

osed

dea

l val

ue ($

m)

B) Licensing deals by phase and value

Deal value Upfront payment2006

2007

2008

2009

2010

2011

2012

2013

Agg

rega

te d

eal v

alue

s ($

m)

Num

ber o

f dea

ls

A) Licensing deals by year and deal value

Number of deals with undisclosed valuesNumber of deals with disclosed valuesTotal disclosed value

Und

iscl

osed

Com

bina

tion

Cyt

otox

ic A

gent

s

GF/

GFR

in

hibi

tor/a

ntag

onis

t

Pro

tein

Kin

ase

Inhi

bito

r Agg

rega

ted

deal

val

ue ($

m)

Num

ber o

f dea

ls

C) Licensing deals by mechanism of action and deal value

Number of deals Sum of Upfront paymentSum of Deal Value

Source: GBI Research, Proprietary Deals Database



7 Appendix

7.1 All Pipeline Drugs by Phase

7.1.1 Discovery

Table 3 Colorectal Cancer Therapeutics, Global, All Pipeline Products (Discovery), 2014

Product name Company Molecule type Mechanism of action Stage of development




7.1.2 Preclinical

Table 4 Colorectal Cancer Therapeutics, Global, All Pipeline Products (Preclinical), 2014





7.1.3 IND/CTA-Filed

Table 5 Colorectal Cancer Therapeutics, Global, All Pipeline Products (IND/CTA-Filed), 2014



7.1.4 Phase I

Table 6 Colorectal Cancer Therapeutics, Global, All Pipeline Products (Phase I), 2014





7.1.5 Phase II

Table 7 Colorectal Cancer Therapeutics, Global, All Pipeline Products (Phase II), 2014





7.1.6 Phase III

Table 8 Colorectal Cancer Therapeutics, Global, All Pipeline Products (Phase III), 2014



7.2 Market Forecasts to 2020

7.2.1 Global

Table 9: Colorectal Cancer Therapeutics, Global, Forecast Data, 2013–2020

Year 2013 2014 2015 2016 2017 2018 2019 2020 CAGR (%)


7.2.2 US

Table 10: Colorectal Cancer Therapeutics, US, Forecast Data, 2013–2020

Year 2013 2014 2015 2016 2017 2018 2019 2020 CAGR (%)




7.2.3 Canada

Table 11: Colorectal Cancer Therapeutics, Canada, Forecast Data, 2013–2020

Year 2013 2014 2015 2016 2017 2018 2019 2020 CAGR (%)


7.2.4 UK

Table 12: Colorectal Cancer Therapeutics, UK, Forecast Data, 2013–2020

Year 2013 2014 2015 2016 2017 2018 2019 2020 CAGR (%)


7.2.5 France

Table 13: Colorectal Cancer Therapeutics, France, Forecast Data, 2013–2020

Year 2013 2014 2015 2016 2017 2018 2019 2020 CAGR (%)




7.2.6 Germany

Table 14: Colorectal Cancer Therapeutics, Germany, Forecast Data, 2013–2020

Year 2013 2014 2015 2016 2017 2018 2019 2020 CAGR (%)


7.2.7 Italy

Table 15: Colorectal Cancer Therapeutics, Italy, Forecast Data, 2013–2020

Year 2013 2014 2015 2016 2017 2018 2019 2020 CAGR (%)


7.2.8 Spain

Table 16: Colorectal Cancer Therapeutics, Spain, Forecast Data, 2013–2020

Year 2013 2014 2015 2016 2017 2018 2019 2020 CAGR (%)


7.2.9 Japan

Table 17: Colorectal Cancer Therapeutics, Japan, Forecast Data, 2013–2020

Year 2013 2014 2015 2016 2017 2018 2019 2020 CAGR (%)




7.3 Market Definitions

Market Coverage

The market includes the eight major markets: the US, the UK, France, Germany, Spain, Italy, Japan and Canada.

The prevalence population is the estimated number of people at any given point of time that are affected by CRC.

The prescription population refers to the number of people taking pharmacological treatment for CRC.

7.4 Abbreviations

5-FU: 5-Fluorouracil

5T4: Trophoblast glycoprotein

ACoT: Annual Cost of Therapy

AE: Adverse Event

Ang: Angiopoietin

APC: Adenomatous Polyposis Coli

ASCO: American Society of Clinical Oncology

ATP: Adenosine Triphosphate

BSC Best Supportive Care

CAGR: Compound Annual Growth Rate

CDF: Cancer Drug Fund

CDK: Cyclin-Dependent Kinase

CEA: Carcinoembyonic Antigen

cGMP-PDE: cyclic Guanosine Monophosphate-Phosphodiesterase

CI: Confidence Interval

CMS: Centers for Medicare & Medicaid Services

CNS: Central Nervous System

CRC: Colorectal Cancer

CTA: Clinical Trial Application

DFMO: Difluoromethylated Ornithine

DFS: Disease Free Survival

DPD: Dihydropyrimidine Dehydrogenase

DTH: Delayed Type Hypersensitivity

dThd: degrading deoxythymidine

ECOG: Eastern Cooperative Oncology Group

EGFR: Epidermal Growth Factor Receptor

EMA: European Medicines Agency

FA: Folinic Acid

FAP: Familial Adenomatous Polyposis

FDA: Food and Drug Administration



FdUMP: 5-fluoro-2'-deoxyuridine monophosphate

FFPE: Formalin-Fixed Paraffin Embedded

FGF: Fibroblast Growth Factor

FGFR: Fibroblast Growth Factor Receptor

FLT3: FMS-Like Tyrosine Kinase 3

FOB: Fecal Occult Blood

FUTP: 5-Fluorouridine Triphosphate

GBM: Glioblastoma Multiforme

GEJ: Gastroesophageal Junction

GI: Gastrointestinal

GIST: Gastrointestinal Stromal Tumors

HDAC: Histone Deacetylases

HER: Human Epidermal Growth Factor Receptor

HGFR: Hepatocyte Growth Factor Receptor

HIPEC: Hyperthermic Intraperitoneal Chemotherapy

HNPCC: Non-Polyposis Colorectal Cancer

HR: Hazard Ratio

IDO: Indoleamine Pyrrole 2,3-Dioxygenase

IGF: Insulin-like Growth Factor

IgG1: Immunoglobulin G1

IL: Interleukin

IND: Investigational New Drug

IPF: Idiopathic Pulmonary Fibrosis

IV: Intravenous

JAK: Janus Kinase 2

kg:

K-Ras: Kirsten rat sarcoma viral oncogene homolog

LV: Leucovorin

m2: square meter

mAb: monoclonal antibody

MAPK: Mitogen-Activated Protein Kinase

MCC: Mutated-in-Colon-Cancer

mCRC: metastatic CRC

mg: milligram

MHLW: Ministry of Health, Labor and Welfare

MLH1: MutL Homolog

MSH: MutS Homolog

mTOR: mammalian Target of Rapamycin



MUC: Mucin

NCI: National Cancer Institute

NF-kB; Nuclear Factor kappa B

NHI: National Health Insurance

NHS: National Health Service

NSCLC: Non-Small-Cell Lung Cancer

ODC: Ornithine Decarboxylase

OPRT: Orotate Phosphoribosyl-Transferase

OS: Overall Survival

p53: tumor protein 53

PACES: Preventing Adenomas of the Colon with Eflornithine and Sulindac

PARP-1: Poly (ADP-Ribose) Polymerase 1

PDE: Phosphodiesterase

PDGF: Platelet Derived Growth Factor

PDGFR: PDGF Receptor

PEG: Polyethylene Glycol

PFS: Progression-Free Survival

PI3K: Phosphatidylinositol-3-Kinase

PIGF: Placental Growth Factor

PKB: Protein Kinase B

PMS: Postmeiotic Segregation Increased

PS: Performance Status

RCC: Renal Cell Carcinoma

RECIST: Response Evaluation Criteria in Solid Tumors

RhD: Rhesus D

RNA: Ribonucleic Acid

RR: Response Rate

SWOG: Southwest Oncology Group

TKI: Tyrosine Kinase Inhibitor

TLR: Toll-Like Receptor

TNIK: TRAF2 and NCK-Interacting Protein Kinase

TNM: Tumor, Nodes and Metastasis

TPI: Thymidine Phosphorylase Inhibitor

TS: Thymidylate Synthase

TTP: Thrombotic Thrombocytopenic Purpura

UTP: Uridine Triphosphate

V2R: Vasopressin V2 Receptor

V1aR: Vasopressin V1a Receptor



V1bR: Vasopressin V1b Receptor

VEGF: Vascular Endothelial Growth Factor

VEGFR: VEGF Receptor

7.5 References

Adams C and Brantner V (2010). Spending on New Drug Development. Health Economics; 19: 130–141.

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

Amado RG, et al. (2008). Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. Journal of Clinical Oncology; 26(10):1626–1634

Amgen (2013). Annual Report and 10-K Filings. Amgen. Available from: http://quote.morningstar.com/stock-filing/Annual-Report/2013/12/31/t.aspx?t=XNAS:AMGN&ft=10-K&d=3ce2d871c79191e361b6b2aa40d97ee2 [Accessed on: November 04, 2014]

Balmaña J et al. (2010). Familial colorectal cancer risk: ESMO Clinical Practice Guidelines. Annals of Oncology; 21(suppl 5): v78-v81

Bibeau F et al. (2006). Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray. Virchows Archiv; 449(3): 281–287

Bruni L et al. (2014). ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in the World. Summary Report 2014-02-20. HPV Information Centre. Available from: http://www.hpvcentre.net/dataquery.php [Accessed October 27, 2014]

Calle EE and Thun MJ (2004). Obesity and cancer. Oncology; 23(38): 6365–6378

Cappell MS (2005). The pathophysiology, clinical presentation, and diagnosis of colon cancer and adenomatous polyps. The Medical Clinics of America: 89(1): 1–42, vii

Center MM et al. (2009a). International trends in colorectal cancer incidence rates. Cancer Epidemiology, Biomarkers and Prevention; 18(6): 1688–1694

Center MM et al. (2009b). Worldwide variations in colorectal cancer. CA: A Cancer Journal for Clinicians; 59(6): 366–378

Chiron M et al. (2014). Differential antitumor activity of aflibercept and bevacizumab in patient-derived xenograft models of colorectal cancer. Molecular Cancer Therapeutics; 13(6):1636–44

Colagiuri B et al. (2012). Does Assessing Patients’ Expectancies About Chemotherapy Side Effects Influence Their Occurrence? Journal of Pain and Symptom Management; Epub

Corley DA et al. (2014). Adenoma detection rate and risk of colorectal cancer and death. New England Journal of Medicine; 370(14): 1298–1306

Cutsem E, et al. (2007). Open-Label Phase III Trial of Panitumumab Plus Best Supportive Care Compared With Best Supportive Care Alone in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer. Journal of Clinical Oncology; 25 (13): 1,658–1,664.

Dickson M (2009). The Cost of New Drug Development. Discovery Medicine; 4 (22): 172–179.

Dolgin E (2009), FDA narrows drug label usage. Nature Publishing Group. Available from: http://www.nature.com/news/2009/090824/full/4601069a.html [Accessed on: September 10, 2014]



7.6 References for Heat Map

Table 18: Colorectal Cancer Market, References for Heat Map

Number Reference

1 Giantonio B et al. (2007). Bevacizumab in Combination With Oxaliplatin, Fluorouracil, and Leucovorin (FOLFOX4) for Previously Treated Metastatic Colorectal Cancer: Results From the Eastern Cooperative Oncology Group Study E3200. Journal of Clinical Oncology; 25 (12): 1,539–1,544.

2 Grothey A et al. (2012). Bevacizumab Beyond First Progression Is Associated With Prolonged Overall Survival in Metastatic Colorectal Cancer: Results From a Large Observational Cohort Study (BRiTE). Journal of Clinical Oncology; 26 (33): 5,326–5,344.

3 Hurwitz H et al. (2004). Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer. New England Journal of Medicine; 350 (23): 2,335–2,342.

4 Kabbinavar et al. (2005). Combined Analysis of Efficacy: The Addition of Bevacizumab to Fluorouracil/Leucovorin Improves Survival for Patients With Metastatic Colorectal Cancer.

5 Kabbinavar F et al. (2009). Addition of Bevacizumab to Fluorouracil-Based First-Line Treatment of Metastatic Colorectal Cancer: Pooled Analysis of Cohorts of Older Patients From Two Randomized Clinical Trials. Journal of Clinical Oncology; 23 (16): 3,706–3,712.

6 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.

7 Saltz L et al. (2008). Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study. Journal of Clinical Oncology; 26 (12): 2,013–2,019.

8 Grothey A et al. (2012). CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):303-12. doi: 10.1016/S0140-6736(12)61900-X. Epub 2012 Nov 22.

9 Kim T W (2014). "CONCUR: A randomized, placebo-controlled phase 3 study of regorafenib (REG) monotherapy in Asian patients with previously treated metastatic colorectal cancer (mCRC)", European Society for Medical Oncology (ESMO) 2014 Congress, Category: Gastrointestinal tumors, colorectal, Session: Proffered Paper session, Poster No.: 500O, 27 Sep 2014

10 Van Cutsem et al. (2013). Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Eur J Cancer. 2014 Jan;50(2):320-31. doi: 10.1016/j.ejca.2013.09.013. Epub 2013 Oct 16.

11 Amado R et al. (2008). Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer. Journal of Clinical Oncology; 26 (10): 1,626–1,634.

12 Cutsem E et al. (2007). Open-Label Phase III Trial of Panitumumab Plus Best Supportive Care Compared With Best Supportive Care Alone in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer. Journal of Clinical Oncology; 25 (13): 1,658–1,664.

13 Douillard J et al. (2010). Randomized, Phase III Trial of Panitumumab With Infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 Alone As First-Line Treatment in Patients With Previously Untreated Metastatic Colorectal Cancer: The PRIME Study. Journal of Clinical Oncology; 28 (31): 4,697–4,705.

14 Hecht J et al. (2009). A Randomized Phase IIIB Trial of Chemotherapy, Bevacizumab, and Panitumumab Compared With Chemotherapy and Bevacizumab Alone for Metastatic Colorectal Cancer. Journal of Clinical Oncology; 27 (5): 672–680.

15 Peeters M et al. (2010). Randomized Phase III Study of Panitumumab With Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) Compared With FOLFIRI Alone As Second-Line Treatment in Patients With Metastatic Colorectal Cancer. Journal of Clinical Oncology; 28 (31): 4,706–4,713.

16 Tol J et al. (2008). A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity. Annals of Oncology; 19: 734–738.

17 Maughan T et al. (2011). Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomized phase 3 MRC COIN trial. Lancet; 377: 2,103–2,114.

18 Sobrero A et al. (2008). EPIC: Phase III Trial of Cetuximab Plus Irinotecan After Fluoropyrimidine and Oxaliplatin Failure in Patients With Metastatic Colorectal Cancer. Journal of Clinical Oncology; 26 (14): 2,311–2,319.

Source: GBI Research



7.7 Research Methodology

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

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

All GBI Research databases are continuously updated and revised. The following research methodology is followed for all databases and reports.

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 extensive 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 that are making the news or that 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.

7.7.2 Secondary Research

The research process begins with extensive secondary research using internal and external sources to gather 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 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



7.7.3 Primary Research

GBI Research conducts hundreds of primary interviews a year with industry participants and commentators in order to validate its data and analysis. A typical research interview fulfills the following functions:

Provides first-hand information on market size, market trends, growth trends, competitive landscape and future outlook

Helps to validate and strengthen secondary research findings

Further develops the analysis team’s expertise and market understanding

Primary research involves email correspondence, telephone interviews and face-to-face interviews for each market, category, segment and sub-segment across a range of geographies.

The participants who typically take part in the process include, but are not limited to:

Industry participants: CEOs, VPs, marketing/product managers, market intelligence managers and national sales managers

Distributors, paramedics and representatives from hospital stores, laboratories and pharmacies

Outside experts: investment bankers, valuation experts, research analysts specializing in specific pharmaceutical markets

Key opinion leaders: physicians and surgeons that specialize in the therapeutic areas

7.7.4 Therapeutic Landscape

Revenues for each indication, geographically, are 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 therapy for each indication is arrived at by considering the cost and 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-use 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.

The forecasting model used by 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 that are prescribed drug treatment (prescription population).

Prescription population is calculated as the percentage of the population diagnosed with a disease (diagnosis population). Diagnosis population is the population diagnosed with a disease expressed as a percentage of the population that is seeking treatment (treatment-seeking population). Prevalence of a disease (diseased population) is the percentage of the total population that suffers from a disease/condition.

Data on the treatment-seeking rate, diagnosis rate and prescription rate, 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 into the forecasting model to account for patient switching and compliance behavior.



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

Annual cost of therapy 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 epidemiology-based forecasting model uses a bottom-up methodology and 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 the subsequent introduction of generics. Historical data for new product launches and generics penetration are used to arrive at robust forecasts. Increase or decrease in prevalence rate, treatment-seeking rate, diagnosis rate and prescription rate are fitted into the forecasting model to estimate market growth rate.

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

Diseased Population

The diseased population for any indication is the prevalence. The prevalence rates are usually obtained from various journals, online publications, sources such as the World Health Organization or associations and foundation websites for that particular disease.

Prescription Population

For any disease, multiple treatment options exist. For example, in cancer treatment various treatment options such as surgery, radiation therapy and drug therapy are available. The prescription population is defined as the number of patients that are prescribed drug therapy. This is calculated as a percentage of the diagnosis population. The prescription population is primarily driven by the age at which the disease is diagnosed, the disease stage, patient health and the cost of drug treatment.



7.7.4.1 Market Size by Geography

The treatment-use pattern and annual cost of therapy in each country has been factored in when deriving the individual country market size.

Forecasting Model for Therapeutic Areas

Figure 23: GBI Research Market Forecasting Model

D is ease P opu lati onGener al Po pulatio n 743,535,048

Q uali fying c ondi tion 1 (Age /S ex/O c c upation e tc )Q uali fying c ondi tion 2 (Age /S ex/O c c upation e tc )

Preva l ence t issu e va lve disease 0.2% 1,784,484 Q uali fying c ondi tion (c om plic ation, s eve rity)DIS EA SE D P OPU LA T IO N 1,784,484

T r eatm en t Flow P a ttern sT rea tm ent S eek i ng R at e (Sy m ptom s / Dis Awareness) 89% 1,588,191 Diagn os is Rat e (C lin ical and D iagn os tic Tes t s) 75% 1,191,143

Prescr iption R ate ( Ph ys ician 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 reatm ents for Valve (Su r g/M ed /N one) -

F ulfi llm en tA vailab ilit y NAW illingness to Us e (Pa tient Perc eptions) NAReady to U se (S u rge ry elig ib ility , R eus e etc ) NA

Affo rd abil it y a t PriceHE as % of G DP s pendA verage Inc om e (per individua l)P at ien t O u t-o f -poc ket Budge t (A nnual)

Budget al loc a tion to one-t im e s urge ryBudget al loc a tion to o the r h ealth needs

A verage Pay or CoverageP at ien t L iab ilityTarge t Pr ic e ( @ 20% pat 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 AL U NIT VO LU MES

Pr icin g pe r Un it 18 ,000$ In f lat ionP rice D ec reas e due to c om pet it ion

M ar ket Va lu e

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

Source: GBI Research

The preceeding figure represents a typical forecasting model followed by GBI Research. As discussed previously, the model is built on treatment flow patterns. The model starts with the general population, then the 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.



7.7.5 Geographical Landscape

GBI Research analyzes eight major geographies: the US, the top five countries in Europe (the UK, Germany, France, Spain and Italy),Japan and Canada. 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. The maximum and minimum estimated market sizes are then provided by adjusting all variables expected to impact upon the market during the forecast period in order to provide the best-case and worst-case scenarios.

Articles from research journals and agency publications such as Rheumatology, Annals of the Rheumatic Diseases, National Institute of Health and ClinicalTrials.gov are the source of data for the estimation of market size and making forecasts.

7.7.6 Pipeline Analysis

This section provides a list of molecules at various stages in the pipeline for various indications. The list is sourced from an internal database and validated for 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. A heat map, sourced from relevant clinical trials, is provided in order to compare these products to one another, in addition to currently marketed products. The latest press releases issued by the companies and news reports are also used to source information for the status of the molecule in the pipeline. This list of pipeline molecules, in conjunction with a list of ongoing and completed clinical trials, is analyzed in this section, and a full breakdown of pipeline molecules and clinical trials by Phase, molecule type and molecular target is provided.

7.8 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.

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

7.9 Contact Us

If you have any queries about this report or would like further information, please contact:

North America: +1 646 395 5477

Europe: +44 (0) 207 406 6777

Asia-Pacific: +91 40 6616 6878

E-mail: [email protected]

7.10 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.

The facts of this report are believed to be correct at the time of publication but cannot be guaranteed. Please note that the findings, conclusions and recommendations that GBI Research delivers will be based on information gathered in good faith from both primary and secondary sources, whose accuracy we are not always in a position to guarantee. As such, GBI Research can accept no liability whatsoever for actions taken based on any information that may subsequently prove to be incorrect.

Colorectal Cancer Therapeutics in Major Developed Markets ... · Colorectal Cancer Therapeutics in...

Documents

Transcript of Colorectal Cancer Therapeutics in Major Developed Markets ... · Colorectal Cancer Therapeutics in...