Rencarex (Renal Cell Carcinoma)- Analysis and Forecasts to Reference Code: GDHC0004RCCDVR Publication Date: March 2012 The Renal Cell Carcinoma (RCC) Disease Therapeutics Market GlobalData s analysis suggests that the combined RCC market in the US, EU-5 (the UK, France, Germany, Italy and Spain) and Japan was worth c. $x billion in 2010 and is likely to grow to c. $xx billion by at a Compound Annual Growth Rate (CAGR) of x%. The worldwide oncology market in 2010 was c. $xx billion and it is expected to grow further at a CAGR of around xx% - xx%. RCC, Global, Market Size Forecasts ($bn), 2010 Source: GlobalData Rencarex Therapeutic Market Rencarex (girentuximab), a product of Wilex AG pharmaceuticals, is a chimeric monoclonal targeted antibody. It is currently in Phase III clinical trial (ARISER) as an adjuvant therapy for patients with non-metastatic clear cell renal cell cancer (RCC) at high risk of relapse after surgery. It is expected to get approval in 2014 in the US and EU. Till date, no drug has been approved by the FDA or EMEA for the adjuvant therapy of non-metastatic clear cell RCC. However, Rencarex is likely to face competition from Sutent and Votrient which are expected to get approval for adjuvant therapy in 2017 in the US and EU. The sales of Rencarex are expected to increase at a CAGR of xx% from 2014 to. Oncology, Worldwide, Market Size Forecasts ($bn), 2005 2015 Source: GlobalData Rencarex, RCC, Global Sales Forecast ($m), 2014 Source: GlobalData Page 1
1 Table of contents 1 Table of contents... 2 1.1 List of Tables... 3 1.2 List of Figures... 4 2 Introduction... 5 2.1 RCC 5 2.1.1 Types of Renal Cell Carcinoma... 5 2.2 RCC Market... 6 2.3 Epidemiology... 6 2.4 Pathophysiology... 9 2.5 Etiology... 9 2.5.1 Cigarette Smoking... 9 2.5.2 Obesity...10 2.5.3 Acquired Cystic Disease...10 2.5.4 Hypertension...10 2.5.5 Family History of Kidney Cancer...10 2.5.6 High Blood Pressure...10 2.5.7 Usage of Certain Medicines...10 2.5.8 Advanced Kidney Disease...10 2.5.9 Gender and Race...10 2.5.10 Genetic and Hereditary Risk Factors...11 2.5.11 Symptoms...11 2.5.12 Diagnosis...12 2.6 GlobalData Report Guidance...14 3 RCC Disease: Market Characterization...15 3.1 RCC Disease Market...15 3.2 RCC Disease Market Forecasts and CAGR...15 3.1 Drivers for the RCC Disease Market...15 3.1.1 High Incidence...16 3.1.2 High Prevalence...17 3.1.3 Emergence of Targeted Therapies...17 3.1.4 Large Unmet Need...17 3.2 Tumor-Node-Metastases (TNM) Classification of RCC...18 3.2.1 Staging...18 3.2.2 Grading...19 3.2.3 Prognosis...19 3.3 Treatment Options in RCC...20 3.3.1 Surgery...20 3.3.2 Radiation therapy...21 3.3.3 Chemotherapy...21 3.3.4 Targeted Therapies...21 3.3.5 Tyrosine Kinase Inhibitors...22 3.3.6 Mammalian Target of Rapamycin (mtor) Inhibitor...22 3.3.7 Vascular Endothelial Growth Factor (VEGF) Inhibitor...23 3.3.8 Treatment by Stage...23 3.4 Classification of Patients with RCC...25 4 Rencarex...26 4.1 Introduction...26 4.2 Mechanism of Action...26 4.3 Clinical Studies...26 Page 2
4.4 Factors Affecting Sales of Rencarex...27 4.4.1 High Efficacy...27 4.4.2 Excellent Safety Profile...27 4.4.3 Large Unmet Need...27 4.4.4 Orphan Drug Status...27 4.5 Drug Evaluation...28 4.5.1 Drug Risk Benefit Score...28 4.5.2 Intensity of Competition...28 4.6 Sales Forecasts...29 4.6.1 Target Patient Pool of Rencarex...29 4.6.2 Dosing...29 4.6.3 Market Penetration...30 4.6.4 Annual Cost of Therapy...30 4.6.5 Sales Projections of Rencarex...31 5 RCC Market: Appendix...39 5.1 Market Definitions...39 5.2 Abberiviations...39 5.3 Research Methodology...39 5.3.1 Coverage...39 5.3.2 Secondary Research...39 5.3.3 Forecasting...40 5.3.4 Number of Patients Approved to Take the Drug...40 5.3.5 Net Penetration of Drug...40 5.3.6 Net Annual Dosing...41 5.3.7 Annual Cost of Therapy...41 5.4 Drug Sales Estimates Model...41 5.5 Disclaimer...41 5.6 Sources...41 1.1 List of Tables Table 1: RCC, Incidences and Mortality, 2008-2030... 8 Table 2: RCC, TNM Classification...18 Table 3: RCC, Fuhrman grading system...19 Table 4: RCC, Treatment Guidelines...20 Table 5: Rencarex, Renal Cell Carcinoma, Phase II Clinical Study Results...27 Table 6: Rencarex, Renal Cell Carcinoma, Global, Sales Estimates ($m), 2014...31 Table 7: Rencarex, Renal Cell Carcinoma, The US, Sales Estimates ($m), 2014...32 Table 8: Rencarex, Renal Cell Carcinoma, The UK, Sales Estimates ($m), 2014...33 Table 9: Rencarex, Renal Cell Carcinoma, France, Sales Estimates ($m), 2014...34 Table 10: Rencarex, Renal Cell Carcinoma, Germany, Sales Estimates ($m), 2014...35 Table 11: Rencarex, Renal Cell Carcinoma, Italy, Sales Estimates ($m), 2014...36 Table 12: Rencarex, Renal Cell Carcinoma, Spain, Sales Estimates ($m), 2014...37 Page 3
1.2 List of Figures Figure 1: Worldwide Incidence and Mortality Distribution of Top 20 Cancers (%), 2010... 7 Figure 2: Total number of cigarettes consumed, The US, 1976-2006... 9 Figure 3: RCC, Global, Market Size Forecasts ($bn), 2010...15 Figure 4: RCC, Global, Incidence (in million), 2008-2030...16 Figure 5: Oncology, Worldwide, Incidence (in million), 2008-2030...16 Figure 6: Classification of Patients with RCC...25 Figure 7: Renal Cell Carcinoma, Rencarex, Drug Model Diagram...29 Figure 8: Rencarex, Renal Cell Carcinoma, Global, Sales Estimates ($m), 2014...31 Figure 9: Rencarex, Renal Cell Carcinoma, The US, Sales Estimates ($m), 2014...32 Figure 10: Rencarex, Renal Cell Carcinoma, The UK, Sales Estimates ($m), 2014...33 Figure 11: Rencarex, Renal Cell Carcinoma, France, Sales Estimates ($m), 2014-...34 Figure 12: Rencarex, Renal Cell Carcinoma, Germany, Sales Estimates ($m), 2014...35 Figure 13: Rencarex, Renal Cell Carcinoma, Italy, Sales Estimates ($m), 2014...36 Figure 14: Rencarex, Renal Cell Carcinoma, Spain, Sales Estimates ($m), 2014...37 Figure 15: Rencarex, Renal Cell Carcinoma, Global, Sales Distribution by Country (%),...38 Figure 16: Patients Approved for the Drug...40 Page 4
2 Introduction 2.1 RCC Renal cell carcinoma (RCC) is classified under Code C-64 according to International Classification of Disease (ICD-10) and is a cancer that develops in the lining of renal tubules, also called as renal cell cancer or renal cell adenocarcinoma.rcc is most common type of kidney cancer and about 9 out of 10 kidney cancers are renal cell carcinomas. RCC is the 15th most common cancer (by incidence) and ninth most common cancer in women accounting for 2-3% of all adult malignancies. RCC accounts for 80 to 85% of primary malignant renal tumors. Transitional cell carcinoma, Wilms' tumor (most often in children), and sarcoma are the less common primary renal cell tumors known. Male to female incidence ratio is 3:2 and people affected are usually between 50 to 70 years of age. In RCC malignant cancer cells are found in the lining of the tubules in the kidney. Cancer originating in the ureter or the renal pelvis is different from RCC. Symptoms usually appear very late, when the tumor may already become large and metastatic. Most metastatic sites include lymph nodes, lungs, adrenal glands, liver, and bone. Renal cell cancer is also called renal adenocarcinoma or hypernephroma. 2.1.1 Types of Renal Cell Carcinoma According to ACS (American Cancer Society) based on microscopic findings RCC has several subtypes 2.1.1.1 Clear cell renal cell carcinoma This is the most common form of renal cell carcinoma. About 7 out of 10 people with renal cell carcinoma have this kind of cancer. The cells that make up clear cell RCC look very pale or clear under a microscope. 2.1.1.2 Papillary renal cell carcinoma This is the second most common subtype about 1 one out of 10 RCC cases. These cancers form little finger-like projections (called papillae) in some, if not most, of the tumor. This subtype is also called chromophilic as the cancer cells look pink under a microscope when stained with certain dyes. 2.1.1.3 Chromophobe renal cell carcinoma This subtype accounts for about 5% (5 cases in 100) of RCCs. The cells of these cancers are also pale, like the clear cells, however comparatively these cells are much larger and have other distinguishing features as well. 2.1.1.4 Collecting duct renal cell carcinoma Very rare subtype and formation of irregular tubes by the cancer cells is the major distinguishing feature. 2.1.1.5 Unclassified renal cell carcinoma Renal cell cancers are labelled as unclassified when they do not into any of the other categories or because there is more than one type of cell present. According to WHO RCC can be classified by three major histological subtypes: Clear cell (crcc, 80-90%) Papillary (prcc, 10-15%) Chromophobe (chrcc, 4-5%) Page 5
2.6 GlobalData Report Guidance The report comprises: A snapshot that includes the global RCC market forecasts from 2010 to. It includes the Global Rencarex sales forecasts from 2014 to. Chapter 1 includes the RCC incidences and mortality in major countries. It also discusses various risk factors associated with RCC. Chapter 2 includes the RCC market forecasts and drivers for the RCC market. Chapter 3 includes the Tumor Node Metastases (TNM) classification of RCC in the US, EU-5 and Japan. Chapter 4 gives a comprehensive Assessment of Rencarex in RCC Market wherein promising results of clinical trials, mode of mechanism and toxicity profile of the drug are discussed. It includes Rencarex s sales forecasts in different countries based on standard pricing of Rencarex and standardized market penetration. Page 14
3 RCC Disease: Market Characterization 3.1 RCC Disease Market 3.2 RCC Disease Market Forecasts and CAGR Figure 3: RCC, Global, Market Size Forecasts ($bn), 2010 Source: GlobalData 3.1 Drivers for the RCC Disease Market Page 15
3.1.1 High Incidence Figure 4: RCC, Global, Incidence (in million), 2008-2030 Source: GlobalData Figure 5: Oncology, Worldwide, Incidence (in million), 2008-2030 Source: GlobalData Page 16
3.1.2 High Prevalence 3.1.3 Emergence of Targeted Therapies 3.1.4 Large Unmet Need Page 17
3.2 Tumor-Node-Metastases (TNM) Classification of RCC 3.2.1 Staging Table 2: RCC, TNM Classification Stages Primary Tumor (T) Regional Lymph Node (N) Distant Metastasis (M) Source: GlobalData, American Joint Committee on Cancer Primary Tumor (T) Regional Lymph Node (N) Distant Metastasis (M) Page 18
3.2.1.1 Stage I 3.2.1.2 Stage IA 3.2.1.3 Stage IB 3.2.2 Grading Table 3: RCC, Fuhrman grading system Grading System (G1-G3) Source: GlobalData, American Joint Committee on Cancer 3.2.3 Prognosis Definition Page 19
5 RCC Market: Appendix 5.1 Market Definitions The Global RCC Market: The global RCC market includes the market for the treatment of renal cell carcinoma in seven countries namely the US, the UK, Germany, France, Spain, Italy and Japan. The Worldwide Oncology Market: The worldwide oncology market includes the market for the treatment of all cancers in the major countries of the world. 5.2 Abberiviations RCC: Renal Cell Carcinoma mrcc: Metastatic Renal Cell Carcinoma TNM: Tumor, Nodes, Metastasis GIST: Gastrointestinal Stromal Tumor NSCLC: Non Small Cell Lung Cancer CAGR: Compounded Annual Growth Rate FDA: Food and Drug Administration NICE: National Institute for Health and Clinical Excellence VEGFR: Vascular Epidermal Growth Factor Receptor PDGFR: Platelet Derived Epidermal Growth Factor Receptor RTK: Receptor Tyrosine Kinase IFNα: Interferon Alfa PFS: Progression Free Survival 5.3 Research Methodology GlobalData s dedicated research and analysis teams consist of experienced professionals with a pedigree in marketing and market research, consulting backgrounds in the pharmaceutical industry and advanced statistical expertise. GlobalData adheres to the Codes of Practice of the Market Research Society (www.mrs.org.uk) and the Society of Competitive Intelligence Professionals (www.scip.org). All GlobalData databases are continuously updated and revised. The following research methodology is followed for all databases and reports. 5.3.1 Coverage The objective of updating GlobalData s coverage is to ensure that it represents the most up to date vision of the industry possible. The drug coverage is based on few key factors such as drug s importance as a treatment option, sales potential of the drug and its innovation potential. GlobalData aims to cover all major marketed and late stage pipeline drugs for a particular indication. The indications which are of particular interest or making the news are prioritized. The scope is to cover the market and drug sales in seven major countries namely the US, the UK, Germany, France, Spain, Italy and Japan. 5.3.2 Secondary Research The research process begins with exhaustive secondary research on internal and external sources, being carried out to source qualitative and quantitative information relating to each market. The secondary research sources that are typically referred to include, but are not limited to: Company websites, annual reports, financial reports, investor presentations and SEC Filings. Page 39
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. 5.3.3 Forecasting GlobalData uses a comprehensive epidemiology-based treatment flow model that uses drug risk benefit score and competition intensity to forecast sales of a drug for a particular therapeutic indication. GlobalData reports cover seven major geographies, namely the US, the UK, Germany, France, Spain, Italy and Japan. The forecasting model used at GlobalData gathers data from various secondary sources. The drug sales are calculated as the product of number of patients who are taking the drug and annual cost of therapy. Annual Drug Sales = Number of patient taking the drug * Annual cost of therapy The number of patients taking the drug can be calculated as below Number of patients taking the drug = Drug Market Penetration * Number of Patients approved to take the drug 5.3.4 Number of Patients Approved to Take the Drug For finding the number of patients approved to take the drug, patient groups are formed based on the functional classification of the disease. Based on this, the overall patients with a disease can be categorized into multiple patient groups. The patient groups, who are not approved to take the drug, are excluded to get the number of patients approved to take drug. Figure 16: Patients Approved for the Drug Source: GlobalData 5.3.5 Net Penetration of Drug After calculating the number of patients approved to take drug, different treatment options available for patients in each patient group are evaluated. The market penetration of the drug will be driven by the potency of the drug, along with its side effect profile and, suitability of alternative treatment options. Drug risk benefit score quantifies efficacy, side effect profile and dosing convenience. The market penetration of a drug in a particular patient group in the forecasting period, is determined by the following factors. All the available drugs in the patient group. The launch and expiration of drugs during the forecasting period. Page 40
The potency of the drug along with its side effect profile and suitability of alternative treatment options. An analogous forecasting methodology is used to account for the introduction of new products, the patent expiries of branded products and the subsequent introduction of generics. 5.3.6 Net Annual Dosing Annual dosing of the drug is calculated by multiplying the recommended dosage of the drug with the treatment regimen. 5.3.7 Annual Cost of Therapy The annual cost of therapy is the product of net annual dosing and the price per unit of the drug. Annual Cost of Therapy = Net Annual Dosing * Price per Unit of Drug. 5.4 Drug Sales Estimates Model Drug sales reports are supported by a comprehensive patient based model, which provides detailed information on key inputs including prevalence rates, market penetration, and annual cost of therapy. The model also includes a unique methodology to evaluate a drug based on its efficacy, safety and other parameters, which are key determiners of a drug s success, and evaluates potential competition that the drug might face during its lifecycle. The drug model also has an inbuilt interactive tool to allow users to input their own assumptions such as market penetration and annual cost of therapy to arrive at their own estimates of sales. This model is available as a part of subscription to GlobalData's Pharma etrack. 5.5 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, GlobalData. 5.6 Sources Pfizer Pharmaceuticals website (http://www.pfizer.com/home/) Annual reports of Pfizer Pharmaceuticals American Association of Urology (http://www.auanet.org/) European Association of Urology (http:/www.uroweb.org/) Globocan (http://www-dep.iarc.fr/) Cancer Journal of Clinicians (http://caonline.amcancersoc.org/) Cancer Research UK (http://caonline.amcancersoc.org/) American Cancer Society (www.cancer.org/) http://jnci.oxfordjournals.org www.fda.gov http://www.clinicaltrials.gov/ www.rxlist.com Page 41