gbihc338mr non-small cell lung cancer market sample 1-10 ... · monoclonal antibodies to diversify...

Non-Small Cell Lung Cancer Market to 2020 New Therapies to Enhance Treatment Segmentation and Drive Growth in an Increasingly Competitive Market

GBI Research Report Guidance

© GBI Research. This is a licensed product and is not to be photocopied GBIHC338MR / Published JUL 2014

GBI Research Report Guidance

Chapter two provides an introduction to Non-Small Cell Lung Cancer (NSCLC), detailing the etiology, tumor characteristics, epidemiology, diagnostic techniques, disease staging and typical prognoses for patients. A detailed analysis of current treatment algorithms and options is also included, alongside safety and efficacy data for all treatments approved in the first, second and third lines, and the maintenance setting.

Chapter three offers detailed analysis of the products currently marketed for NSCLC, detailing their key characteristics, including safety and efficacy, clinical trial outcomes, tolerability, dosing, administration, pricing, and overall competitive strength. These products are also compared in a comprehensive heat map.

Chapter four provides detailed analysis of the pipeline for NSCLC 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, and provides a primary endpoint analysis of NSCLC clinical trials. Promising late-stage pipeline molecules are also analyzed and assessed in terms of their potential competitive strength.

Chapter five contains market forecasts for the NSCLC market, covering epidemiology, treatment usage patterns, pricing and market size for the 2013–2020 forecast period. Eight major markets – the US, Canada, Germany, the UK, France, Italy, Spain and Japan – are covered, and data are presented on a country-by-country level, with further analysis of key market drivers and barriers.

Chapter six describes the major deals that have taken place in the global NSCLC 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 are also included, organized by the location of company headquarters.


Executive Summary

Executive Summary

Pipeline Entries to Drive NSCLC Market Growth

The Non-Small Cell Lung Cancer (NSCLC) market will undergo considerable growth from $XX billion in 2013 to $XX billion in 2020 at a Compound Annual Growth Rate (CAGR) of XX%. The added value will be derived from an abundance of new product launches relatively early in the forecast period. Many of these therapies will target the second line of treatment; both the first-line treatment of patients with non-squamous histology and the maintenance setting will remain relatively unchanged by 2020. New second-line therapies include immunostimulants such as ramucirumab and nivolumab, which have shown clinical benefits, but which will face difficulties due to the increasingly crowded second-line setting. Currently, pharmaceutical treatment is limited to late-stage patients. However, vaccine therapies such as Lucanix (belagenpumatucel-L) will launch in the forecast period, for patients with stage II or IIIA NSCLC, in the currently sparse adjuvant setting. Although vaccine treatments have been unsuccessful so far in NSCLC – the most recent example being GSK’s MAGE-A3 vaccine failing its Phase III trial – Lucanix has shown large improvements to survival rates in its initial clinical trials.

Monoclonal Antibodies to Diversify Squamous Cell Treatment

Over the forecast period to 2020, several new additions to the NSCLC treatment paradigm will transform the treatment landscape. Many of these will be monoclonal Antibodies (mAbs), which instigate an immune response to the tumor rather than directly affecting cancer cells. Crucially, some of these mAbs will be indicated for patients with squamous cell histology, whose current treatment options are very limited and primarily consist of chemotherapy. Squamous cell histology accounts for approximately XX% of the NSCLC population, and pipeline products, such as Yervoy (ipilimumab) in the first-line treatment and nivolumab in the second-line, will add greater diversity to the treatment algorithm, with both having shown clinical benefits in early-stage trials. Access to these premium treatments in this under-represented segment will be one of the primary drivers for growth in the overall NSCLC market.

Efforts are being made to understand the molecular characterization of NSCLC tumors in order to identify cancer-cell-specific targets for therapy, based on the success of targeted therapies Tarceva (erlotinib) and Xalkori (crizotinib). However, novel therapies targeting these molecules, such as Kirsten Rat Sarcoma viral oncogene homolog (KRAS), have so far been unsuccessful in the late-stage pipeline, meaning that the range of mutant signal pathway molecules targeted by therapy will remain largely unchanged over the forecast period and mAb immunotherapies targeting cancer or T-cell antigens will have a much larger impact than small-molecule-targeted signal inhibitors.

Major Patents to Expire Late in Forecast Period

Patents for Alimta (pemetrexed), Avastin (bevacizumab), Tarceva, and Iressa (gefitinib) will all expire between 2017 and 2020. Alimta is a vital therapy for non-squamous patients and is in many cases the preferred course of treatment, combined with cisplatin. Generic availability following patent expiry in 2017 will make non-squamous chemotherapy cheaper, although the market value will ultimately continue to rise despite generic erosion, due to successful pipeline entrants. Tarceva is widely used in first-line Epidermal Growth Factor Receptor (EGFR) positive patients, and generally in the second-line setting. Its patent will not expire until 2020 however, meaning that the effects will not be felt during the 2014–2020 forecast period. Iressa is not widely used, and therefore the patent expiration in 2017 will have little impact.

Early Diagnosis to Remain Uncommon

The vast majority (XX%) of NSCLC cases are diagnosed in stage IIIB or IV, at which point surgical resection is not possible, making pharmacological intervention the best course of action. The number of treatment settings for late-stage patients, specifically first-line, second-line and maintenance, adds significant value to the market. Should the number of early diagnoses increase, fewer patients would require extensive chemotherapy or targeted therapy, meaning that the market would decrease. However, improvements to the diagnosis of NSCLC are limited. Identifying Stage I–IIIA tumors remains difficult, despite the identification of high-risk groups, such as smokers. Over the forecast period, the characterization of tumors will likely improve, and more potential biomarkers will be identified. Screening and diagnostic technology will not change significantly over the forecast period however, meaning the number of patients diagnosed in early stages will remain at approximately XX%.


Table of Contents

1 Table of Contents

1 Table of Contents ................................................................................................................................. 4 1.1 List of Tables ............................................................................................................................. 7 1.2 List of Figures............................................................................................................................ 8

2 Introduction........................................................................................................................................10 2.1 Disease Introduction ................................................................................................................10 2.2 Epidemiology ...........................................................................................................................11 2.3 Etiology and Pathophysiology ...................................................................................................11

2.3.1 Adenocarcinoma ..............................................................................................................12 2.3.2 Squamous Cell Carcinoma ................................................................................................15 2.3.3 Large Cell Carcinoma ........................................................................................................17 2.3.4 Immunotherapy ...............................................................................................................18

2.4 Symptoms ...............................................................................................................................18 2.5 Diagnosis .................................................................................................................................18 2.6 Prognosis .................................................................................................................................21 2.7 Treatment ...............................................................................................................................21

2.7.1 Treatment Algorithm........................................................................................................22 2.7.2 First-Line Treatment .........................................................................................................26 2.7.3 Maintenance Therapy ......................................................................................................33 2.7.4 Second-Line Therapy ........................................................................................................35 2.7.5 Third-Line Therapy ...........................................................................................................39 2.7.6 Adjuvant Therapy .............................................................................................................39

3 Marketed Products .............................................................................................................................41 3.1 Overview .................................................................................................................................41 3.2 Chemotherapies – Various .......................................................................................................41

3.2.1 Cisplatin ...........................................................................................................................41 3.2.2 Carboplatin ......................................................................................................................42 3.2.3 Vinorelbine ......................................................................................................................42 3.2.4 Paclitaxel .........................................................................................................................42 3.2.5 Docetaxel .........................................................................................................................43 3.2.6 Gemcitabine ....................................................................................................................43

3.3 Alimta – Eli Lilly ........................................................................................................................44 3.4 Abraxane – Celgene Corporation ..............................................................................................45 3.5 Tarceva – Roche.......................................................................................................................46 3.6 Iressa – AstraZeneca ................................................................................................................47 3.7 Gilotrif – Boehringer Ingelheim ................................................................................................48 3.8 Xalkori – Pfizer .........................................................................................................................49 3.9 Avastin (bevacizumab) – Roche ................................................................................................50 3.10 Marketed Products Heatmap ...................................................................................................51 3.11 Conclusion ...............................................................................................................................53

4 NSCLC Pipeline ....................................................................................................................................54 4.1 Overview .................................................................................................................................54 4.2 Mechanisms of Action in the Pipeline .......................................................................................56 4.3 Clinical Trials ............................................................................................................................60

4.3.1 Failure Rate .....................................................................................................................60 4.3.2 Clinical Trial Duration .......................................................................................................62 4.3.3 Clinical Trial Size...............................................................................................................65 4.3.4 Clinical Trial Primary Endpoints.........................................................................................68

4.4 Late-Stage Pipeline Product Profiles .........................................................................................70 4.4.1 Custirsen – Teva Pharmaceutical Industries .......................................................................70 4.4.2 Halaven – Eisai .................................................................................................................71


Table of Contents

4.4.3 Dacomitinib – Pfizer .........................................................................................................72 4.4.4 Vargatef – Boehringer Ingelheim ......................................................................................74 4.4.5 Necitumumab – Eli Lilly ....................................................................................................75 4.4.6 Ganetespib – Synta Pharmaceuticals ................................................................................77 4.4.7 Zykadia– Novartis ............................................................................................................78 4.4.8 Yervoy – Bristol Myers Squibb ...........................................................................................79 4.4.9 Nivolumab – Ono Pharmaceuticals/Bristol-Myers Squibb ..................................................81 4.4.10 MK-3475 – Merck .............................................................................................................82 4.4.11 RG7446 – Roche ...............................................................................................................83 4.4.12 Cyramza– Eli Lilly .............................................................................................................83 4.4.13 Tavocept – BioNumerik Pharmaceuticals ..........................................................................85 4.4.14 Tecemotide – Merck Serono .............................................................................................86 4.4.15 Tertomotide – KAEL-GemVax ............................................................................................87 4.4.16 Lucanix – NovaRx Corporation ..........................................................................................88 4.4.17 Bevacizumab Biosimilar – Various .....................................................................................89

4.5 Safety and Efficacy Heatmap ....................................................................................................90 4.6 Conclusion ...............................................................................................................................93

4.6.1 Product Competitiveness Framework ................................................................................93 4.6.2 Future Treatment Algorithm .............................................................................................95

5 Market Forecast..................................................................................................................................98 5.1 Geographical Markets ..............................................................................................................98

5.1.1 Global Markets ................................................................................................................98 5.1.2 North America ............................................................................................................... 101 5.1.3 Top Five EU Countries ..................................................................................................... 103 5.1.4 Japan ............................................................................................................................. 107

5.2 Drivers and Barriers ............................................................................................................... 108 5.2.1 Drivers ........................................................................................................................... 109 5.2.2 Barriers .......................................................................................................................... 109

6 Strategic Consolidations .................................................................................................................... 111 6.1 Major Co-Development deals ................................................................................................. 111

6.1.1 Merck Enters into Co-Development Agreement with Endocyte ......................................... 113 6.1.2 Exelixis Enters into a Co-Development Agreement with Genentech .................................. 113 6.1.3 CancerVax Enters into an Agreement with CIMAB and YM Biosciences............................. 113 6.1.4 SFJ Pharma Enters into Co-Development Agreement with Pfizer for Dacomitinib .............. 114 6.1.5 OxOnc Development Enters into Co-Development Agreement with Pfizer for Crizotinib .... 114

6.2 Major Licensing Deals ............................................................................................................ 114 6.2.1 Merck Serono Enters into Licensing Agreement with Ono Pharma ................................... 116 6.2.2 Astellas Pharma Enters into Licensing Agreement with Aveo Pharma............................... 116 6.2.3 Clovis Oncology Enters into a Licensing Agreement with Avila Therapeutics ..................... 117 6.2.4 Novartis Enters into Licensing Agreement with Antisoma ................................................ 117 6.2.5 Cell Therapeutics Enters into Licensing Agreement with Novartis ..................................... 117

7 Appendix .......................................................................................................................................... 119 7.1 References ............................................................................................................................ 130 7.2 Market Definition .................................................................................................................. 135 7.3 Abbreviations ........................................................................................................................ 135

7.3.1 Research Methodology ................................................................................................... 137 7.3.2 Secondary Research ....................................................................................................... 137 7.3.3 Marketed Product Profiles .............................................................................................. 138 7.3.4 Late-Stage Pipeline Candidates ....................................................................................... 138 7.3.5 Comparative Efficacy and Safety Heat Map for Marketed and Pipeline Products .............. 138 7.3.6 Product Competitiveness Framework .............................................................................. 138 7.3.7 Pipeline Analysis............................................................................................................. 139


Table of Contents

7.3.8 Forecasting Model ......................................................................................................... 140 7.3.9 Deals Data Analysis ........................................................................................................ 140

7.4 Contact Us ............................................................................................................................. 141 7.5 Disclaimer.............................................................................................................................. 141


Table of Contents

1.1 List of Tables

Table 1: Non-Small Cell Lung Cancer Market, Global, Tumor Node Metastasis Classification, 2014 .........20 Table 2: Non-Small Cell Lung Cancer Market, Global, Eastern Co-operative Oncology Group Criteria, 2014

...............................................................................................................................................21 Table 3: Non-Small Cell Lung Cancer Market, Global, Treatment Options, 2014 .....................................23 Table 4: Non-Small Cell Lung Cancer Market, Global, Stage IIIB–IV Treatment Options, 2014 .................26 Table 5: Non-Small Cell Lung Cancer Market, Global, Chemotherapy Treatment, 2014 ..........................27 Table 6: Non-Small Cell Lung Cancer Market, Global, Chemotherapy Treatment by Regimen, 2014 ........28 Table 7: Non-Small Cell Lung Cancer Market, Global, Pipeline, Preclinical, 2014 ................................... 119 Table 8: Non-Small Cell Lung Cancer Market, Global, Pipeline, Phase I, 2014 ....................................... 121 Table 9: Non-Small Cell Lung Cancer Market, Global, Pipeline, Phase II, 2014 ...................................... 123 Table 10: Non-Small Cell Lung Cancer Market, Global, Pipeline, Phase III, 2014 ..................................... 125 Table 11: Non-Small Cell Lung Cancer Market, Global, Pipeline, Pre-registration, 2014 .......................... 126 Table 12: Non-Small Cell Lung Cancer Market, Global, Pipeline, Undisclosed, 2014 ................................ 126 Table 13: Non-Small Cell Lung Cancer Market, Global, Market Forecast, 2013-2020 .............................. 127 Table 14: Non-Small Cell Lung Cancer Market, US, Market Forecast, 2013-2020 .................................... 128 Table 15: Non-Small Cell Lung Cancer Market, Canada, Market Forecast, 2013-2020 ............................. 128 Table 16: Non-Small Cell Lung Cancer Market, UK, Market Forecast, 2013-2020 .................................... 128 Table 17: Non-Small Cell Lung Cancer Market, France, Market Forecast, 2013-2020 .............................. 128 Table 18: Non-Small Cell Lung Cancer Market, Germany, Market Forecast, 2013-2020 .......................... 129 Table 19: Non-Small Cell Lung Cancer Market, Italy, Market Forecast, 2013-2020 .................................. 129 Table 20: Non-Small Cell Lung Cancer Market, Spain, Market Forecast, 2013-2020 ................................ 129 Table 21: Non-Small Cell Lung Cancer Market, Japan, Market Forecast, 2013-2020 ............................... 130


Table of Contents

1.2 List of Figures

Figure 1: Non-Small Cell Lung Cancer Market, Global, Molecular Characteristic Frequency (%), 2014 ......12 Figure 2: Non-Small Cell Lung Cancer Market, Global, Non-Squamous Late-Stage Treatment Algorithm,

2014 .......................................................................................................................................24 Figure 3: Non-Small Cell Lung Cancer Market, Global, Squamous Late-Stage Treatment Algorithm, 2014 25 Figure 4: NSCLC, Global, Marketed Products Heatmap, 2013 ..................................................................52 Figure 5: Non-Small Cell Lung Cancer, Global, Pipeline Summary, 2014...................................................56 Figure 6: Non-Small Cell Lung Cancer, Global, Pipeline Mechanisms of Action Overview, 2014 ................57 Figure 7: Non-Small Cell Lung Cancer, Global, Pipeline Mechanisms of Action Breakdown, 2014 .............59 Figure 8: Non-Small Cell Lung Cancer, Global, Clinical Trial Attrition Rates (%), 2006–2014 .....................61 Figure 9: Non-Small Cell Lung Cancer, Global, Clinical Trial Mechanism of Action Failure Rates by Phase

(%), 2006–2014 .......................................................................................................................62 Figure 10: Non-Small Cell Lung Cancer, Global, Clinical Trial Duration (months), 2006–2013 .....................63 Figure 11: Non-Small Cell Lung Cancer, Global, Clinical Trial Duration by Molecule Type (months), 2006–

2013 .......................................................................................................................................64 Figure 12: Non-Small Cell Lung Cancer, Global, Clinical Trial Duration by Mechanism of Action (months),

2006–2013 .............................................................................................................................65 Figure 13: Non-Small Cell Lung Cancer, Global, Clinical Trial Size per Product (participants), 2006–2013 ...66 Figure 14: Non-Small Cell Lung Cancer, Global, Clinical Trial Size per Product by Molecule Type

(participants), 2006–2013 .......................................................................................................67 Figure 15: Non-Small Cell Lung Cancer, Global, Clinical Trial Size per Product by Mechanism of Action

(months), 2006–2013 ..............................................................................................................68 Figure 16: Non-Small Cell Lung Cancer, Global, Clinical Trial Primary Endpoints, 2006–2013 .....................69 Figure 17: Non-Small Cell Lung Cancer, Global, Clinical Trial Primary Endpoint Combinations by Phase (%),

2006–2013 .............................................................................................................................70 Figure 18: Non-Small Cell Lung Cancer Pipeline, Global, Custirsen Annual Sales ($m), 2018–2020 .............71 Figure 19: Non-Small Cell Lung Cancer Pipeline, Global, Halaven Annual Sales ($m), 2016–2020 ...............72 Figure 20: Non-Small Cell Lung Cancer Pipeline, Global, Dacomitinib Annual Sales ($m), 2014–2020 .........74 Figure 21: Non-Small Cell Lung Cancer Pipeline, Global, Vargatef Annual Sales ($m), 2015–2020 ..............75 Figure 22: Non-Small Cell Lung Cancer Pipeline, Global, Necitumumab Annual Sales ($m), 2015–2020 ......77 Figure 23: Non-Small Cell Lung Cancer Pipeline, Global, Ganetespib Annual Sales ($m), 2016–2020 ..........78 Figure 24: Non-Small Cell Lung Cancer Pipeline, Global, Zykadia Annual Sales ($m), 2014–2020 ................79 Figure 25: Non-Small Cell Lung Cancer Pipeline, Global, Yervoy Annual Sales ($m), 2015–2020 .................81 Figure 26: Non-Small Cell Lung Cancer Pipeline, Global, Nivolumab Annual Sales ($m), 2015–2020 ...........82 Figure 27: Non-Small Cell Lung Cancer Pipeline, Global, Cyramza Annual Sales ($m), 2015–2020 ..............85 Figure 28: Non-Small Cell Lung Cancer Pipeline, Global, Tavocept Annual Sales ($m), 2017–2020 .............86 Figure 29: Non-Small Cell Lung Cancer Pipeline, Global, Tertomotide Annual Sales ($m), 2017–2020 ........88 Figure 30: Non-Small Cell Lung Cancer Pipeline, Global, Lucanix Annual Sales ($m), 2016–2020 ................89 Figure 31: Non-Small Cell Lung Cancer , Global, Safety and Efficacy Heatmap, 2013 ..................................91 Figure 32: Non-Small Cell Lung Cancer , Global, Marketed Products Heatmap, 2013 .................................92 Figure 33: Non-Small Cell Lung Cancer Market, Global, Product Competitiveness Framework, 2014 ..........94 Figure 34: Non-Small Cell Lung Cancer Market, Global, Non-Squamous Future Treatment Algorithm 2020 96 Figure 35: Non-Small Cell Lung Cancer Market, Global, Squamous Future Treatment Algorithm ................97 Figure 36: Non-Small Cell Lung Cancer Market, Global, Treatment Patterns (‘000), 2013–2020 .................99 Figure 37: Non-Small Cell Lung Cancer Market, Global, Market Size ($bn), 2013–2020 ............................ 100 Figure 38: Non-Small Cell Lung Cancer Market, North America, Treatment Usage Patterns (‘000), 2013–

2020 ..................................................................................................................................... 101 Figure 39: Non-Small Cell Lung Cancer Market, North America, Annual Cost of Treatment ($), 2013–2020

............................................................................................................................................. 102 Figure 40: Non-Small Cell Lung Cancer Market, North America, Market Size, 2013–2020 ........................ 103 Figure 41: Non-Small Cell Lung Cancer Market, Top Five EU Countries, Treatment Patterns (‘000), 2013–

2020 ..................................................................................................................................... 104 Figure 42: Non-Small Cell Lung Cancer Market, Top Five EU Countries, Annual Cost of Treatment ($), 2013–

2020 ..................................................................................................................................... 105 Figure 43: Non-Small Cell Lung Cancer Market, Top Five EU Countries, Market Size ($m), 2013–2020 ..... 106 Figure 44: Non-Small Cell Lung Cancer Market, Japan, Treatment Usage Patterns (‘000), 2013–2020 ...... 107 Figure 45: Non-Small Cell Lung Cancer Market, Japan, Annual Cost of Treatment ($), 2013–2020 ........... 108 Figure 46: Non-Small Cell Lung Cancer Market, Japan, Market Size ($bn), 2013–2020 ............................. 108


Table of Contents

Figure 47: Non-Small Cell Lung Cancer, Global, Co-Development Deals by Region, 2006–2014 ................ 111 Figure 48: Non-Small Cell Lung Cancer, Global, Number of Co-Development Deals, 2006–2014 .............. 112 Figure 49: Non-Small Cell Lung Cancer, Global, Co-Development Deals by Phase, 2006–2014 ................. 113 Figure 50: Non-Small Cell Lung Cancer, Global, Licensing Deals by Region, 2006–2014 ............................ 115 Figure 51: Non-Small Cell Lung Cancer, Global, Number of Licensing Deals, 2006–2014 .......................... 116 Figure 52: Non-Small Cell Lung Cancer, Global, Licensing Deals by Phase, 2006–2014 ............................. 116


Introduction

2 Introduction

2.1 Disease Introduction

Lung cancer is the most second most common cancer type globally, second only to prostate cancer in males and breast cancer in females. However, it is the most common cause of cancer mortality globally, responsible for one in five cancer-related deaths (Globocan, 2012). Lung cancer can be split into two distinct histologies: NSCLC, and Small Cell Lung Cancer (SCLC), based on the cells affected. NSCLC is the most prevalent form of the two, and accounts for XX% of cases. NSCLC can be further divided into three major histology subsets: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Each of these subsets has different characteristics, and responds differently to certain treatments, although histological differentiation between subtypes can be difficult due to limited patient tissue availability and overlap between features.

Lung cancer has strong, positive correlation with smoking cigarettes, cigars and pipes (Lee et al., 2012). There also occupational hazards that can increase the risk of lung cancer; these include exposure to radon gas, asbestos, radiation, and air pollution. There is also a genetic basis to lung cancer, meaning that an individual does not have to be exposed to environmental carcinogens to develop the condition. Mutations in several genes such as Kirsten Rat Sarcoma viral oncogene homolog (KRAS) and Epidermal Growth Factor Receptor (EGFR) can cause lung cancer, meaning a large amount of research is being undertaken, both on these genes and also searching for other genes (Simon, 2012).

The prognosis for NSCLC is very poor, which is shown by the current five-year survival rate of only XX% (American Cancer Society, 2013). Prognosis generally improves the earlier the cancer is diagnosed, but many cases are not diagnosed until the latter stages, where the cancer cannot be cured, only treated with a combination of chemotherapy, radiotherapy and targeted therapy. These often have serious side effects and only prolong life by several months. Early detection of NSCLC can mean that surgery is an option for treatment; this can remove the tumor and improve the prognosis significantly.

The large prevalence and death rates associated with NSCLC mean it attracts a lot of attention from publicly funded research and pharmaceutical companies. There is broad scope to improve the treatment paradigm for NSCLC, which is dominated by chemotherapies that have been the standard of care for many years. Such therapies inhibit cell replication and as a result are often highly toxic to healthy cells. Despite the dominance of these therapies in treatment, the need for more efficacious therapies has led to NSCLC treatment becoming increasingly personalized, causing the market to become increasingly segmented. The identification of various molecular aberrations in cancer cells has opened up the possibility of targeted treatments, which have a smaller treatment population, but are typically safer and more efficacious. The prevalence of a particular aberration can vary according to ethnicity, gender and smoking habits of a population. As the market currently stands, most patients will receive treatment with chemotherapy, aside from EGFR patients and Anaplastic Lymphoma receptor tyrosine Kinase (ALK) positive patients, who can receive mutation-specific targeted therapy.

NSCLC Pipeline

© GBI Research. This is a licensed product and is not to be photocopied GBIHC338MR / Published JUL 2014 Page 54

4 NSCLC Pipeline

4.1 Overview

Overall, the current marketed therapies insufficiently meet the needs of the NSCLC population, and there are many areas of treatment in which pipeline products could improve upon existing therapies. These are primarily by increasing the range of targeted therapies, decreasing toxicity of chemotherapies, treatments for drug-resistant patients, and a general improvement in prognosis. As NSCLC is such a major cause of death worldwide, it attracts much attention from the pharmaceutical industry, which has resulted in an active NSCLC pipeline of XX different therapeutics. Analysis has shown that the most active Phase of development is currently Phase II, with XX% of pipeline molecules represented here. Preclinical and Phase I drugs also represent large portions of the pipeline, with XX% and XX% of therapeutics respectively, as seen in Figure 5A.

The most common molecule types throughout the pipeline are shown in Figure 5B. Small molecules are in the clear majority, accounting for XX% of the drugs in this class. Chemotherapies and many targeted therapies are small molecules, which explains their high proportion. Immunotherapies are most commonly monoclonal antibodies, and their increasing popularity explains why antibodies are the second-most abundant molecule type in the pipeline. The other biologic category primarily consists of biosimilars, but it also contains novel peptides and recombinant proteins. Knowledge of NSCLC immunotherapy has caused the rise in pipeline vaccine options, which are designed to offer a low-toxicity, prolonged response, particularly for those in the often-overlooked early-stage adjuvant setting.

The majority of pipeline molecules are administered either intravenously or orally. Figure 5C shows that these make up a combined XX% of the pipeline routes of administration. Oral therapies have the benefit of ease of use and system-wide distribution, whereas intravenous therapies can mean a higher bioavailability of the drug and faster distribution. The other category consists of several routes of administration that are much rarer in the pipeline, such as intramuscular injection and parenteral administration.

NSCLC Pipeline


The vast majority of pipeline drugs are novel compounds, as shown by Figure 5D, which are defined as new active pharmaceutical ingredients that are not currently approved in any market or indication. The other remainder is made up predominantly of repositioned drugs, which are already marketed for a different indication, or generic compounds. For example, the immunotherapy Yervoy has had success in melanoma, and is currently in Phase III and being repositioned for NSCLC and set for first-line approval in squamous cell patients. There are generic versions of the chemotherapies Taxol and Taxotere in development, some of which are used in other oncology indications, and have been reformulated for better delivery. For example, Docecal is a formulation of docetaxel with a nano-drug delivery system used in prostate cancer. The repositioned drugs are mainly distributed between Phase II and III, whereas the generic drugs are relatively evenly split between earlier stages, with one paclitaxel variant in the pre-registration stage. There are a small number of biosimilars, mainly of bevacizumab, that are in Phase II and preparing for market launch following Avastin patent expiry in 2019.

Proportionally, the number of drugs of each molecule type in each Phase is relatively similar, in particular between small molecules, antibodies, vaccines and other biologics. This would suggest that there has not been a shift in the performance or preference for one particular molecule type over the others in recent years, as this would have created a disproportionately large number of one molecule type in the earlier phases.

As Figure 5E shows, small molecules are the preferred molecule type in all stages of development. Only in Phase III is it at a similar frequency to biologics. This provides evidence for a lower attrition rate of biologics compared to other molecules, as proportionally, more make it to Phase III (discussed in section 4.3.1).

NSCLC Pipeline


Figure 5: Non-Small Cell Lung Cancer, Global, Pipeline Summary, 2014

Discovery

Preclinical

IND/CTA-filed

Phase I

Phase II

Phase III

Pre-registration

Unknown

A) Pipeline by Stage of Development

Total: XX

Small molecule

Biologic

Vaccine

Other DNANull

B) Pipeline by Molecule Type

Total: XX

Dis

cove

ry

Prec

linic

al

IND

/CTA

-fil

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Pha

se I

Pha

se II

Pha

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I

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-re

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ratio

n

Unk

now

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Num

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s

D) Pipeline by Program Type

BiosimilarGenericRepositionedNovel

Dis

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Prec

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Pha

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Pha

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Pha

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I

Pre-

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E) Pipeline by Molecule Type and Stage of Development

NullVaccineOtherDNABiologicSmall molecule

Oral

Intravenous

Intradermal

Subcutaneous

Intravenous, Oral

Parenteral

Intramuscular

C) Pipeline by Route of Administration

Total: XX

Source: GBI Research, Proprietary Pipeline Database

NSCLC Pipeline


4.6.2 Future Treatment Algorithm

The following diagram details revised versions of the treatment algorithms discussed in section 2.7.1. These are based on the scenario of all promising pipeline products reaching the market in the same settings and the combinations in which they are currently being tested. It therefore represents the potential NSCLC treatment algorithm in 2020. The green boxes represent new market entries and dashed line represents products that are likely to be combined.

NSCLC Pipeline

© GBI Research. This is a licensed product and is not to be photocopied GBIHC338MR / Published JUL 2014Page 96

Figure 34: Non‐Small Cell Lung Cancer Market, Global, Non‐Squamous Future Treatment Algorithm 2020

Advanced Non-squamous diagnosis

XX EGFR-

XX XX

XXXX

XX

XX XX Pemetrexed XX

XX XX XX

XX XX PemetrexedXXXX

XX

XX

XX

1st

Mai

nten

ance

2nd

XX

XX

Source: GBI Research

Abbreviations: ALK: Anaplastic Lymphoma Kinase; BSC: ; EGFR: Epidermal Growth Factor Receptor; PS: Performance Score

Market Forecast


5 Market Forecast

5.1 Geographical Markets

Market Forecast


5.1.1 Global Markets

NSCLC is not the most prevalent of cancers, with only XX million cases estimated in the eight major markets (US, Canada, Germany, France, UK, Italy, Spain and Japan), due to its very high incidence rates and poor survival rates. In 2012, there were XX new cases and XX deaths worldwide. This high mortality rate makes NSCLC one of the most common causes of cancer death globally (Ferlay et al., 2012). Based on US findings, incidence rates have been declining at a rate of XX% each year since 2002 (Howlader et al., 2014).

The treatment population of NSCLC is lower than the total prevalent population due to a large proportion of patients having a performance score of greater than two, which renders them ineligible for many forms of chemotherapy and targeted therapy. Also, as many early-stage patients receive surgery or radiotherapy over pharmacological treatment, they were excluded from the treatment population analysis. These patients receive supportive care only and do not receive pharmaceutical treatment. Overall, the growth in NSCLC patients shown in Figure 36 will contribute to the increasing market value as the treatable population increases.

Figure 36: Non-Small Cell Lung Cancer Market, Global, Treatment Patterns (‘000), 2013–2020

2013 2014 2015 2016 2017 2018 2019 2020

Pat

ient

s ('0

00)

Prevalence population Treatment population


Figure 37 displays the growth in the global NSCLC market value from $XX billion in 2013 to $XX billion in 2020 at a CAGR of XX%. The market will begin to rise after 2015 following the introduction of several new therapies. It then maintains steady growth until 2020, a result of the continued uptake of these drugs. Of the premium-price new drugs entering the market, nivolumab is expected to have the largest market impact as it is showing very promising results in squamous cell patients in clinical trials. This drug is expected to quickly capture a large proportion of market share. It also will be approved in non-squamous patients, making it the first targeted therapy available for all histologies. Yervoy is expected to be approved in 2015 in the US and 2016 in the EU for the first-line treatment of patients with squamous histology. Adjuvant therapies such as tertomotide may also boost market growth as this setting is relatively sparse.

Market Forecast


Should clinical trial results for adjuvant therapies show meaningful improvements to PFS then these drugs will be a significant addition to early-stage treatment.

Figure 37: Non-Small Cell Lung Cancer Market, 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

Projected CAGR 2013–2020: XX%Low CAGR 2013–2020: XX%Peak CAGR 2013–2020: XX%


The peak outcome scenario of the global forecast will grow at a CAGR of XX% growth takes into account therapies such as ramucirumab, which have met trial endpoints but are awaiting specific trial data, acquiring a large market segment at a premium price. However, given the difficulties that Avastin and Xalkori have had with reimbursement, particularly in the UK, strong clinical trial results will be required for this scenario to occur.

Numerous factors could lead to the low outcome scenario, such as drugs failing pivotal Phase III trials and not being approved by regulatory bodies. HTAs, such as NICE, have already hesitated to recommend and reimburse therapies such as Xalkori as it bases decisions on cost-effectiveness in comparison with market leaders. Most recently, a MET-targeted therapy, onartuzumab and adjuvant vaccine GSK-15792932A have failed pivotal Phase III trials despite promising Phase II results. Onartuzumab, a MET inhibitor, failed to show any meaningful improvements to efficacy (OS or PFS) against Tarceva monotherapy in MET-positive patients during a pre-specified interim analysis. Safety results for the two treatment arms were comparable, suggesting that current late-stage therapies need to improve efficacy in their intent-to-treat population, compared to current standards of treatment in order to be granted approval. With the high volume of Phase III drugs due to enter the market and a XX% Phase III failure rate (section 4.3.1) there is a strong chance that many drugs will reach the market.

Strategic Consolidations


6 Strategic Consolidations

6.1 Major Co-Development deals

Analysis showed that XX co-development deals regarding NSCLC therapeutics took place between 2006 and 2014. This shows a relatively low collaborative effort between pharmaceutical companies despite the prevalence and lethality of NSCLC. The US is the most common location of co-development deals and Canada is its most common partner country. Several major players in oncology, such as Pfizer, Eli Lilly and Merck have headquarters in the US, which explains the high prevalence of deals made in North America.. In Europe, the greatest number of deals was conducted in Germany and Switzerland (Figure 47).

Figure 47: Non-Small Cell Lung Cancer, Global, Co-Development Deals by Region, 2006–2014

Source: GBI Research, deals database

Strategic Consolidations


There has been an increase in the number of co-development deals made since 2011. During the 2007–2009 periods only one deal per year was made. No deals were made in 2010. The reason for the increase in co-development deals, peaking in 2012 with XX deals, is not attributable to one particular reason although the rising costs and risk of clinical trial development will make collaborative projects more appealing. (Figure 48).

Figure 48: Non-Small Cell Lung Cancer, Global, Number of Co-Development Deals, 2006–2014

2006 2007 2008 2009 2010 2011 2012 2013

Tota

l num

ber o

f dea

ls

Number of undisclosed deals Number of disclosed deals

Source: GBI Research, deals database

Appendix


7 Appendix

Table 7: Non-Small Cell Lung Cancer Market, Global, Pipeline, Preclinical, 2014

Product Name Company Stage of Development

Appendix


Source: GBI Research Proprietary Pipeline Products Database

Appendix


Table 8: Non-Small Cell Lung Cancer Market, Global, Pipeline, Phase I, 2014


Appendix



Appendix


Table 9: Non-Small Cell Lung Cancer Market, Global, Pipeline, Phase II, 2014


Appendix



Appendix


Table 10: Non-Small Cell Lung Cancer Market, Global, Pipeline, Phase III, 2014


Appendix



Table 11: Non-Small Cell Lung Cancer Market, Global, Pipeline, Pre-registration, 2014

Drug/project name Company Stage of development


Table 12: Non-Small Cell Lung Cancer Market, Global, Pipeline, Undisclosed, 2014

Drug/project name Company Stage of development


Appendix


Table 13: Non-Small Cell Lung Cancer Market, Global, Market Forecast, 2013-2020

2013 2014 2015 2016 2017 2018 2019 2020

Prevalence Population ('000)

Treatment Population ('000)

Maximum Market Size ($m)

Projected Market Size ($m)

Minimum Market Size ($m)

Predicted Sales of Cisplatin ($m)

Predicted Sales of Carboplatin ($m)

Predicted Sales of Vinorelbine tartate ($m)

Predicted Sales of Paclitaxel ($m)

Predicted Sales of Docetaxel ($m)

Predicted Sales of Gemcitabine ($m)

Predicted Sales of Pemetrexed disodium ($m)

Predicted Sales of nab-Paclitaxel ($m)

Predicted Sales of Erlotonib ($m)

Predicted Sales of Gefitinib ($m)

Predicted Sales of Crizotinib ($m)

Predicted Sales of Afatinib ($m)

Predicted Sales of Bevacizumab ($m)

Predicted Sales of Custirsen sodium ($m)

Predicted Sales of Dacomitinib ($m)

Predicted Sales of Tavocept ($m)

Predicted Sales of Eribulin mesylate ($m)

Predicted Sales of Ganetespib ($m)

Predicted Sales of Ipilimumab ($m)

Predicted Sales of LDK378 ($m)

Predicted Sales of Necitumumab ($m)

Predicted Sales of Nivolumab ($m)

Predicted Sales of Ramucirumab ($m)

Predicted Sales of Tertomotide ($m)

Predicted Sales of Nintedanib ($m)

Predicted Sales of Belagenpumatucel-L ($m)


Appendix


Table 14: Non-Small Cell Lung Cancer Market, US, Market Forecast, 2013-2020

2013 2014 2015 2016 2017 2018 2019 2020



ACoT ($)





Table 15: Non-Small Cell Lung Cancer Market, Canada, Market Forecast, 2013-2020

2013 2014 2015 2016 2017 2018 2019 2020



ACoT ($)





Table 16: Non-Small Cell Lung Cancer Market, UK, Market Forecast, 2013-2020

2013 2014 2015 2016 2017 2018 2019 2020



ACoT ($)





Table 17: Non-Small Cell Lung Cancer Market, France, Market Forecast, 2013-2020

2013 2014 2015 2016 2017 2018 2019 2020



ACoT ($)





Appendix


Table 18: Non-Small Cell Lung Cancer Market, Germany, Market Forecast, 2013-2020

2013 2014 2015 2016 2017 2018 2019 2020



ACoT ($)





Table 19: Non-Small Cell Lung Cancer Market, Italy, Market Forecast, 2013-2020

2013 2014 2015 2016 2017 2018 2019 2020



ACoT ($)





Table 20: Non-Small Cell Lung Cancer Market, Spain, Market Forecast, 2013-2020

2013 2014 2015 2016 2017 2018 2019 2020



ACoT ($)





Appendix


Table 21: Non-Small Cell Lung Cancer Market, Japan, Market Forecast, 2013-2020

2013 2014 2015 2016 2017 2018 2019 2020



ACoT ($)





7.1 References

Aberle D, et al. (2013) Computed Tomography Screening for Lung Cancer: Has it Finally Arrived? Implications of the National Lung Screening Trial. Journal of Clinical Oncology; 31(8): 1002–1008

Aisner D and Marshall C (2012). Molecular Pathology of Non-Small Cell Lung Cancer. A Practical Guide. Molecular Diagnostics Consultation; 138: 332–346

American Cancer Society (2013). Cancer Facts and Figures 2013. American Cancer Society. Available from http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf

American Cancer Society (2014). Non-Small Cell Lung Cancer Survival Rates by Stage. American Cancer Society. Available from http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-survival-rates [Accessed April 29, 2014]

Antonoff M and D’Chuna J (2012). Non-Small Cell Lung Cancer: The Era of Targeted Therapy. Lung Cancer: Targets and Therapy; 2012(3): 31–41

ASH (2014). Smoking Statistics. Action on Smoking and Health. Available from http://www.ash.org.uk/files/documents/ASH_93.pdf

Bang YJ (2011). The Potential for Crizotinib in Non-Small Cell Lung Cancer: A Perspective Review. Therapeutic Advances in Medical Oncology; 3(6): 279–291

Boehringer Ingelheim (2013). LUME- Lung 2: a Multicenter, Randomized, Double-blind, Phase III Study of Nintedanib plus Pemetrexed versus Placebo plus Pemetrexed in Patients with Advanced Non-squamous Non-small Cell Lung Cancer after Failure of First-line Chemotherapy. Boehringer Ingelheim. Available from: http://www.boehringer-ingelheim.com/content/dam/internet/opu/com_EN/document/05_clinical_trials/qrcode/asco_2013/1199_14_poster.pdf

Brown T, et al (2013). Clinical Effectiveness and Cost-Effectiveness of First-Line Chemotherapy for Adult Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer: A Systematic Review and Economic Evaluation. Health Technology Assessment; 17 (31)

Brunsvig P, et al. (2011). Telomerase Peptide Vaccination in NSCLC: A Phase II Trial in Stage III Patients Vaccinated after Chemoradiotherapy and an 8-Yeart Update on a Phase I/II trial. Clinical Cancer Research; 17(21): 6,847–6,857

Cancer Research UK (2013). Lung Cancer Incidence Statistics. Cancer Research UK. Available from http://www.cancerresearchuk.org/cancer-info/cancerstats/types/lung/incidence/uk-lung-cancer-incidence-statistics [Accessed April 07, 2014]

Central Intelligence Agency. (2013). The World Factbook: Japan. Central Intelligence Agency. Available from https://www.cia.gov/library/publications/the-world-factbook/geos/ja.html [Accessed April 07, 2014]

Appendix


Solomon B, et al. (2013). Current Status of Targeted Therapy for Anaplastic Lymphoma Kinase-Rearranged Non-Small Cell Lung Cancer. Clinical Pharmacology & Therapeutics; 95(1): 15–23

Swami U, et al. (2012). Eribulin – A Review of Preclinical and Clinical Studies. Critical Reviews in Oncology/Hematology; 81(2): 163-184

The Clinical Lung Cancer Genome Project and Network Genomic Medicine (2013). A Genomics-Based Classification of Human Lung Tumors. Science Translational Medicine; 5(209): 209ra153

Tomasini P, et al. (2012). Ipilimumab: Its Potential in Non-Small Cell Lung Cancer. Therapeutic Advances in Medical Oncology; 4(2): 43–50

Topalian S, et al. (2012). Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer. The New England Journal of Medicine; 366: 2443–2454

Weiss J, et al. (2010). Adjuvant Cisplatin and Docetaxel for Non-Small Cell Lung Cancer: The Hospital of the University of Pennsylvania Experience. Journal of Thoracic Oncology; 5(5): 667–672

Yang J, et al. (2012). Afatinib for Patients with Lung Adenocarcinoma and epidermal Growth Factor Receptor Mutations (LUX-Lung 2): A Phase 2 Trial. The Lancet Oncology; 13(5): 539–548

Zhang K, et al. (2013). Pluripotent Stem Cell Protein Sox2 Confers Sensitivity to LSD1 Inhibition in Cancer Cells. Cell Reports; 5(2): 445–457

Zhou C, et al. (2011). Erlotinib versus Chemotherapy as First-Line Treatment for Patients with Advanced EGFR Mutation Positive Non-Small Cell Lung Cancer (OPTIMAL,CTONG-0802): A Multicenter, Open-Label, Randomized, Phase III Study. The Lancet Oncology; 12(8): 735–742

7.2 Market Definition

The global NSCLC market comprises the top eight markets of the US, the UK, Germany, France, Spain, Italy, Japan and Canada.

The top five EU countries comprise 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 NSCLC.

7.3 Abbreviations

AIS: Adenocarcinoma In Situ

AKT: Protein kinase B

ALK: Anaplastic Lymphoma Kinase

ATP: Adenosine Triphosphate

Bim: Bcl2-interacting mediator of cell death

BMS: Bristol Myers Squibb

BSC: Best Supportive Care

CAGR: Compound Annual Growth Rate

CT: Computer Tomography

CTLA4: Cytotoxic T-Lymphocyte-associated Antigen 4

DB: Double Blind

DDR2: Discoidin Domain Receptor 2

DFS: Disease Free Survival

ECOG: Eastern Cooperative Oncology Group

EGFR: Epidermal Growth Factor Receptor

EML4: Echinoderm Microtubule-associated Like protein 4

Appendix


EU: European Union

FDA: Food and Drug Administration

FGFR: Fibroblast Growth Factor Receptor

HDAC: Histone Deacetylase

HER2: Human Epidermal growth factor Receptor 2

HGFR: Hepatocyte Growth Factor Receptor

Hsp90: Heat Shock Protein 90

HTA: Health Technology Assessment

irPFS: Immune Related Progression Free Survival

KRAS: Kirsten Rat Sarcoma viral oncogene homolog

LDCT: Low-Dose Computed Tomography

MAGEA1: Melanoma Associate Antigen 1

MC: Multi-Centre

MEK: Mitogen activate protein Kinase kinase

MTD: Maximum Tolerated Dose

mTOR: mammalian Target Of Rapamycin

MUC1: Mucin 1

NICE: National Institute for Health and Care Excellence

NSCLC: Non-Small Cell Lung Cancer

OAE: Other Adverse Events

OL: Open Label

ORR: Overall Response Rate

OS: Overall Survival

PC: Placebo Controlled

PD1: Programmed cell Death receptor 1

PDGFR: Platelet-Derived Growth Factor Receptor

PDL-1: Programmed Death Ligand 1

PFS: Progression Free Survival

PIK3CA: Phosphoinositide 3-Kinase Catalytic subunit α

PS: Performance Score

PTEN: Phosphatase and Tensin homologue

R: Randomized

SAE: Serious Adverse Events

SCLC: Small Cell Lung Cancer

SOX2: Sry-related HMG box 2

TGFb: Transforming Growth Factor beta

TGF-β2: Transforming Growth Factor: Beta 2

TNM: Tumor Node Metastasis

Appendix


VEGF: Vascular Endothelial Growth Factor

VEGFR: Vascular Endothelial Growth Factor Receptor

WHO: World Health Organization

7.3.1 Research Methodology

GBI Research aims to help clients within the life sciences industries to better understand their business environment, compete successfully within it, and achieve growth.

Our goal is to be the business intelligence partner of choice for companies in the life sciences arena that are looking for meaningful, innovative and evidence-based analysis to inform their key decision-making.

Our coverage extends to the major indications across all therapy areas with a particular focus on oncology, CNS and immunology and a weighting towards indications demonstrating significant innovation in early-stage development. Our complex proprietary data methodologies drive our specialisms in indications with clearly established therapeutic landscapes, significant pipeline activity and a high proportion of approved products with market exclusivity.

Everything we do at GBI Research is rooted in extensive data validation, interrogation and analysis. Our R&A teams are constantly looking for ways to evolve our products in order to provide ever more understanding and transparency around what is really happening in the market.

There are a number of key themes running through all of our product offerings that serve to define our proposition and position in a crowded market:

Data integrity:

GBI Research has full access to comprehensive, market-leading proprietary databases covering marketed and pipeline products, clinical trials, and licensing and co-development deals. In addition to the daily database updates made by that specific team, GBI Research validates all data used in research reports, ensuring an exceptionally high degree of data accuracy.

Data are refreshed immediately prior to publication to ensure the final report reflects any changes that took place during the authoring effort.

Innovative and meaningful analytical techniques and frameworks:

GBI Research recognizes the value of highly accurate raw data, but this is simply the platform.

The entire proposition is built around understanding clients’ needs related to business intelligence, and the ambition to develop novel proprietary data interrogation methodologies to extract meaningful and innovative data sets and provide insightful analyses.

Evidence based analysis and insight:

Proprietary data interrogation methodologies are applied to provide visibility over such vital and tangible data parameters as clinical trial attrition rates versus industry averages, clinical trial endpoint design, product competitiveness benchmarking and multi-scenario forecasting.

7.3.2 Secondary Research

The research process begins with extensive secondary research utilizing proprietary databases and external sources, including 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 databases

Relevant patent and regulatory databases

National government documents, statistical databases and market reports

Appendix


Procedure registries

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

7.3.3 Marketed Product Profiles

The marketed products section provides an overview of the market landscape and gives qualitative profiles of the leading marketed therapies. These profiles describe molecule type, mechanism of action, companies involved in development and marketing, overall clinical and commercial strength, and future prospects. Emphasis is placed on analyzing efficacy and safety data in order to comparatively determine the strongest products available for treatment and assess the clinical and commercial positioning in the current market. In addition, our marketed product profiles assess the clinical and commercial threats and opportunities in the context of late-stage pipeline products in order to provide an evidence-based outlook and perspective for product performance during the forecast period.

Where available, historical revenue data are also provided.

7.3.4 Late-Stage Pipeline Candidates

This section consists of qualitative profiles of drugs in the late stages of the developmental pipeline. The focus here is predominantly on Phase III drugs and, depending on clinical and commercial potential, Phase II drugs.

The profiles cover areas including, but not limited to, a drug’s molecule type and mechanism of action, companies involved in its development, performance in clinical trials specifically relating to efficacy and safety endpoints, and overall clinical and commercial potential. Typically, a revenue forecast for the drug candidate in the covered indication is also provided. This includes peak, medium and low-variance ranges throughout the forecast period, which take into consideration variable factors with a high degree of inherent unpredictability such as marketing approval of pipeline products, clinical uptake and potential competition, drug price inflation rates and many more.

7.3.5 Comparative Efficacy and Safety Heat Map for Marketed and Pipeline Products

The comparative efficacy and safety heat map provides a visual representation of the comparative clinical profile of each marketed product based on available clinical trial data. GBI Research aims to aggregate and integrate all available clinical trial efficacy and safety data, organized by the respective endpoints into heat maps to assist in direct performance benchmarking of each drug.

The heat map uses conditional formatting to color-code the performance of each marketed drug from strongest to weakest. This is applied to each clinical trial endpoint, allowing us to determine the strongest performer in each endpoint category. A dark blue color indicates the strongest performers in that category, whereas light gray colors indicate weaker performers.

7.3.6 Product Competitiveness Framework

The product competitiveness frameworks translate the clinical trial data in heat maps into performance benchmarks that express the comparative efficacy and safety performance as a ratio. The safety and efficacy data by endpoint are aggregated and compared to the strongest marketed product in each parameter. The baseline, as defined by the strongest marketed product on each endpoint, is defined as 1. The performance of all other marketed and pipeline products is expressed as a comparative ratio in comparison to the strongest performing product on that endpoint. Dark blue values indicate strong performers in that category and lighter gray values indicate weaker performers. This includes qualitative assessment of product features that offer meaningful differentiation from competitor’s products, such as route of administration and dosage/administration frequency. Overall, this type of analysis helps to determine the potential impact of a specific new drug on the market, as well as the future competitive landscape.

Appendix


7.3.7 Pipeline Analysis

7.3.7.1 Overall Pipeline

This section analyzes proprietary pipeline data and provides a thorough overview of the current pipeline landscape for the indication in question. Using proprietary data analysis techniques, the pipeline is broken down by stage of development, molecule type, mechanism of action and/or molecular target. Each of these categories is subject to further granulation depending on the level of data available and any observed trends or findings. It is broken down by program type to determine the degree of novelty within the pipeline. Each drug development program is defined as being novel, generic or repositioned using methodologies and processes and drawing upon multiple databases, including market and pipeline datasets. Repositioned drugs are defined as those that are already marketed for another indication and that are now in development for the indication being assessed. Novel products are defined as containing active pharmaceutical ingredients that are currently not approved in the market, whereas generic products include approved compounds that are no longer under patent. The accuracy of the data is validated using external sources such as company websites.

Like all sections within the report, the data analysis provides the basis for in-depth written discussion, which determines the broader implications of the results obtained.

7.3.7.2 Clinical Trials

The clinical trial landscape for each indication is comprehensively profiled using proprietary clinical trial data. The factors assessed include, but are not limited to, clinical trial failure rate, size and duration and endpoint analysis. Each is analyzed by clinical stage of development.

7.3.7.2.1 Failure Rate

Failure rate analysis helps to determine the risk profile associated with drug development for the indication in question. The failure rate is defined as the percentage of products that fail to progress to the next stage of clinical development or reach marketing approval, as is the case for products in Phase III. Inactive development programs are defined as those for which no progress has been made and for which no further updates have been disclosed for over four years.

This analysis is typically subject to further granulation, such as failure rate by Phase, mechanism of action and molecule type, to provide further insight into the risks associated with the development of certain classes of drugs and product technology.

7.3.7.2.2 Clinical Trial Size

Clinical trial size assesses the mean and median subject recruitment size of clinical trials by Phase and compares the respective indications against the wider therapy area or industry benchmarks. This is commonly analyzed further by molecule type and mechanism of action.

7.3.7.2.3 Clinical Trial Duration

Like clinical trial size, clinical trial duration analyzed and disclosed the mean and median duration (in months) of clinical trials by Phase and molecule type/mechanism of action.

7.3.7.2.4 Clinical trial Endpoint Analysis

A clinical trial endpoint is a measure from which a decision can be made to accept or reject the null hypothesis. The primary and secondary endpoints used in clinical trials can be used to provide insight into the patient outcomes driving drug development.

The analysis is designed to extract the primary and secondary outcome measures used across all clinical trials in the indication, whether different safety, efficacy or pharmacokinetic endpoints. These data are then graphically presented to display the most prominent primary and secondary endpoints.

Trends in primary and secondary endpoints are assessed by Phase of development and, when possible, over a specified timeframe to identify any changing patterns in clinical trial design.

Appendix


7.3.8 Forecasting Model

This GBI Research report 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.

Our forecasting model uses an epidemiology-based approach, in which sales for each product are calculated based on the cost of the drug, and the number of patients using it.

Initially, based on peer-reviewed literature, the disease prevalence is calculated and extrapolated with historic trends and any other relevant inputs gathered from the literature. In the same way, the fraction of prevalent patients that is diagnosed and the proportion of diagnosed patients that is ultimately treated are also calculated.

If relevant, the treatment population is then divided into segments using any available inputs from scientific literature. For example, in oncology indications it is common for us to divide the patient population based on the stage of disease. Each drug may appear in more than one segment within this model and, if used as part of a combination of products, revenues are calculated on single product levels across all segments and combinations.

The use of each drug within each segment (as a percentage) is estimated as accurately as possible, primarily using treatment guidelines, primary research and any other relevant peer-reviewed data inputs for each indication. The market penetration of pipeline products in their first few years after approval is estimated based primarily on published clinical trial data, with the safety and efficacy profiles of each pipeline drug being compared against any other competitors in their patient segment(s).

Pipeline products that are expected to fulfill an unmet need and perform better than marketed products are typically given higher distributions than those that are not. While efficacy and safety data are usually the most important criteria for making these estimates, other characteristics such as the route of administration and dosing convenience are weighted more strongly in relevant indications.

The cost of each drug is estimated based on its cost per gram (cost of one unit divided by the size of each unit in grams) and the number of grams taken by each patient in a single year (or a course of therapy). For the purposes of this model, different formulations for a single drug with different dosages (for example, a pediatric and adult formulation) are treated as separate entities.

For pipeline drugs, the cost is estimated based on a benchmark of existing marketed products (typically within the indication). Based on their ability to fulfill unmet needs and compete effectively with marketed products, a percentage markup (or occasionally a markdown) versus its benchmark is assigned. This benchmark may be an individual product (such as a direct competitor) or an average of existing products.

The cost is adjusted to take into account inflation of pharmaceutical products and any estimated effects of patent expiries (with biologics having a slower and weaker price erosion than small molecules following patent expiry). Finally, based on percentage distributions, a weighted average cost of each drug is estimated for all patients treated for the disease. This can then be multiplied by the treatment population to arrive at a sales estimate for that drug, and the total sales of all drugs is then the overall market size.

From this primary forecast, peak and low market sizes and drug sales are estimated based on potential variations and uncertainties in price inflation, patent expiry, distribution shifts, pipeline product market penetration, and drug pricing for pipeline products. Inherently unpredictable events such as policy changes are not modeled directly in the scenarios, but are accounted for in the numeric inputs. These multiple scenarios aim to supplement the primary forecast with an accurate, transparent picture of the inherent uncertainty of the future market, and the likely range of outcomes.

7.3.9 Deals Data Analysis

This section includes analysis of GBI Research proprietary strategic deals data relevant to the indication being assessed. The two major deal types analyzed are co-development deals and licensing deals.

When analyzing co-development and licensing deals data, the parameters assessed are often consistent, although there can be some variation depending on data availability. Firstly, deals are analyzed by country, value and year.

Analysis by country includes the use of network charts, which visually represent links between different nations to visualize where companies involved in deals are headquartered and to identify deal hubs.

Appendix


The deals data are analyzed further to display the number of deals by stage of development, molecule type and mechanism of action. Qualitative analysis of the major deals within the indication is also provided.

7.5 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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