gbihc358mr rheumatoid arthritis therapeutics in asia ... · market. globally, there are multiple...

THERAPY ANALYSIS

Rheumatoid Arthritis Therapeutics in Asia-Pacific Markets to 2021 - Novel IL-6 and JAK Inhibitors

to Stimulate Moderate Growth Despite Brand Erosion of Blockbuster Anti-TNFs

Report Code: May 2015 Published: GBIHC358MR

www.gbiresearch.com

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

GBIHC358MR / Published MAY 2015

GBI Research Report Guidance

Chapter three provides an overview of the disease, its symptoms, etiology, pathophysiology, diagnosis, classification, epidemiology, prognosis, staging and treatment options

Chapter four provides a detailed profiling and comparative analysis in terms of safety and efficacy for currently marketed products in the RA market.

Chapter five presents a detailed pipeline analysis for the disease, including individual product profiles, a comparative efficacy and safety profile heat map analysis of the most promising pipeline products as well as analyses on the distribution of molecule types across the RA developmental pipeline, the molecular targets of pipeline drug candidates and the developmental program types. In addition, detailed analyses of the clinical trial failure rates, the clinical trial durations by phase and clinical trial sizes, by participant numbers.

Chapter six provides market forecasts for countries across the globe, with special attention given to the APAC countries: India, Australia, China and Japan. The multiple scenario forecasts take into account a range of factors that are likely to vary and provide a clear perspective on the level of the potential degree of variance in the market sizes.

Chapter seven covers the major deals that have taken place in the disease market in recent years. Coverage includes co-development deals and licensing agreements, which are segmented on the basis of geography and total value. A concomitant analysis of the licensing deal values for products by molecule types and molecular targets is also provided.


GBIHC358MR / Published MAY 2015

Executive Summary

Sustained Growth in the Rheumatoid Arthritis Therapeutics Market Over Forecast Period

The advent of biologic Disease-Modifying Anti-Rheumatic Drugs (DMARD) has boosted the Rheumatoid Arthritis (RA) market tremendously over the last two decades. Growth is expected to continue at a moderate pace during the forecast period from $XX billion in 2014 to $XX billion in 2021 at a Compound Annual Growth Rate (CAGR) of XX% in the Asia-Pacific (APAC) markets of India, Australia, China and Japan. Japan accounted for majority of the market in 2014 with a XX% share, followed by India, China and Australia with XX%, XX%, and XX% respectively.

The entry of new therapies over the forecast period will stimulate market growth; promising pipeline candidates anticipated to have a strong impact include Eli Lilly and Incyte’s baricitinib, Johnson & Johnson (J&J) and GlaxoSmithKline’s (GSK) sirukumab, and Sanofi and Regeneron’s sarilumab. The treatment population is set to grow in the four APAC territories despite a small decline in the prevalence population in Japan, which is a key driver for growth in market size. The loss of the patent exclusivity of major second-line biologic anti-Tumor Necrosis Factor (TNF) therapies such as Enbrel, Remicade and Humira by the end of the forecast period is not expected to reduce the market size due to slow generic erosion. However, this presents a major barrier to growth in market size, which is anticipated to be modest in spite of the entry of promising pipeline candidates.

Rheumatoid Arthritis Market, Asia-Pacific, Market Size ($bn), 2014–2021

2014 2015 2016 2017 2018 2019 2020 2021

Ma

rke

t siz

e (

$b

n)

Low variance Medium variance High variance Projected

Source: GBI Research, Proprietary Marketed Products Database

Increasingly Crowded Market for Second-Line Therapies Improving Treatment Options for Moderate-to-Severe Rheumatoid Arthritis Patients

RA is a chronic, progressive and currently incurable autoimmune disease that primarily affects joints. It is characterized by synovial inflammation and gradual bone erosion over many years, and disease progression results in stiffness and pain, especially in the hands and feet, which hinders patient mobility. Without treatment, the disease leads to joint destruction and disability. Prior to 1998, treatment options were limited to small-molecule disease-modifying therapies, such as Methotrexate (MTX), sulfasalazine and anti-malarials. However, while MTX is efficacious in controlling RA symptoms in a large percentage of patients, approximately XX% are unresponsive to these first-line drugs. The approval of revolutionary biological therapies, including Enbrel, Remicade and Humira, for the treatment of RA patients that are refractory to MTX triggered unparalleled growth in the market. Globally, there are multiple biological therapies, including monoclonal antibodies (mAb), biosimilars and therapeutic proteins, all competing as second-line therapies for this sub-population. Over the past 16 years, the therapeutic market for RA has become extremely competitive as a result of the high number of new drug approvals.


GBIHC358MR / Published MAY 2015 Page 5

1 Table of Contents

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

2 Introduction .............................................................................................................................................................. 10 2.1 Disease Introduction ................................................................................................................................ 10 2.2 Symptoms ...................................................................................................................................................... 11 2.3 Etiology ........................................................................................................................................................... 11 2.4 Pathophysiology .......................................................................................................................................... 11 2.5 Diagnosis ...................................................................................................................................................... 12

2.5.1 Physical Examination ........................................................................................................................ 12 2.5.2 Blood Tests ......................................................................................................................................... 12 2.5.3 1987 Rheumatoid Arthritis Classification .................................................................................... 13 2.5.4 2010 ACR-EULAR Classification Criteria for Rheumatoid Arthritis ...................................... 13

2.6 Epidemiology ............................................................................................................................................... 14 2.7 Co-morbidities and Complications ........................................................................................................ 14 2.8 Disease Progression ................................................................................................................................. 15 2.9 Pharmacotherapy Algorithm ................................................................................................................... 15 2.10 Treatment Options ..................................................................................................................................... 16

2.10.1 Pharmacological ................................................................................................................................ 17 2.10.2 Methotrexate ...................................................................................................................................... 17 2.10.3 Hydroxychloroquine ......................................................................................................................... 17 2.10.4 Leflunomide ........................................................................................................................................ 17 2.10.5 Sulfasalazine ....................................................................................................................................... 17 2.10.6 Cyclosporine ....................................................................................................................................... 18 2.10.7 Prograf (tacrolimus) ........................................................................................................................... 18 2.10.8 Xeljanz (tofacitinib) ............................................................................................................................ 18

2.11 Other Non-biologics .................................................................................................................................. 18 2.11.1 Non-steroidal Anti-inflammatory Drugs ...................................................................................... 18 2.11.2 Painkillers ............................................................................................................................................ 18 2.11.3 Glucocorticoids .................................................................................................................................. 18

2.12 Biologic Disease-Modifying Anti-rheumatic Drugs ........................................................................... 19 2.12.1 Tumor Necrosis Factor Alpha Inhibitors ..................................................................................... 19 2.12.2 Interleukin Inhibitors ......................................................................................................................... 19 2.12.3 Other Biologics that Target B- and T-Cell Antigens ................................................................ 19

2.13 Disease Scoring Methods for Measuring Treatment Efficacy ..................................................... 20 2.13.1 Radiographic Progression ............................................................................................................ 20 2.13.2 Clinical Disease Activity Index and Simplified Disease Activity Index ............................. 20 2.13.3 Disease Activity Score-28 ............................................................................................................. 20 2.13.4 American College of Rheumatology.......................................................................................... 20 2.13.5 Health Assessment Questionnaire ............................................................................................ 20

3 Marketed Products .................................................................................................................................................. 21 3.1 Overview ....................................................................................................................................................... 21 3.2 Small-Molecule Disease-Modifying Anti-rheumatic Drugs ............................................................. 21

3.2.1 Methotrexate-Based Products....................................................................................................... 21 3.2.2 Xeljanz (tofacitinib) – Pfizer .......................................................................................................... 22

3.3 Biologic Disease-Modifying Anti-rheumatic Drugs .......................................................................... 23 3.3.1 Remicade (infliximab) – Johnson & Johnson, Merck ............................................................. 23 3.3.2 Humira (adalimumab) – AbbVie ................................................................................................... 24 3.3.3 Enbrel (etanercept) – Amgen, Pfizer and Takeda Pharmaceutical ................................... 25 3.3.4 Rituxan (rituximab) – Genentech, Biogen IDEC ....................................................................... 27



3.3.5 Orencia (abatacept) – Bristol-Myers Squibb ........................................................................... 28 3.3.6 Simponi (golimumab) – Johnson & Johnson, Merck ............................................................ 29 3.3.7 Cimzia (certolizumab pegol) – UCB ........................................................................................... 30 3.3.8 Kineret (anakinra) – Swedish Orphan Biovitrum ...................................................................... 31 3.3.9 Actemra (tocilizumab) – Roche .................................................................................................... 32 3.3.10 Comparative Safety and Efficacy ................................................................................................. 33

3.4 Unmet Need ................................................................................................................................................ 36 4 Product Pipeline ...................................................................................................................................................... 37

4.1 Overview ...................................................................................................................................................... 37 4.2 Pipeline Distribution by Phase of Development, Molecule Type, Route of Administration

and Novelty ................................................................................................................................................. 37 4.3 Pipeline Distribution by Mechanism of Action ................................................................................. 40

4.3.1 Cytokine Inhibitors ........................................................................................................................... 42 4.3.2 B- and T-cells ..................................................................................................................................... 43 4.3.3 Intracellular Kinases ........................................................................................................................ 44

4.4 Clinical Trial Analysis ................................................................................................................................ 45 4.4.1 Overall Attrition Rate ....................................................................................................................... 45 4.4.2 Attrition Rate by Phase, Molecule Type and Target .............................................................. 46 4.4.3 Average Clinical Trial Size by Molecule Type ......................................................................... 48 4.4.4 Average Clinical Trial Size by Mechanism of Action............................................................... 51 4.4.5 Average Clinical Trial Duration per Molecule Type by Product ........................................ 52 4.4.6 Average Clinical Trial Duration per Mechanism of Action by Product ............................. 54 4.4.7 Primary and Secondary Endpoints ............................................................................................. 55 4.4.8 Summary ............................................................................................................................................ 56

4.5 Promising Pipeline Drugs ....................................................................................................................... 56 4.5.1 Baricitinib – Eli Lilly ......................................................................................................................... 56 4.5.2 Sarilumab – Regeneron Pharmaceuticals/Sanofi ................................................................... 57 4.5.3 Sirukumab – Johnson & Johnson .............................................................................................. 58 4.5.4 Decernotinib – Vertex Pharmaceuticals ................................................................................... 58 4.5.5 Masitinib ............................................................................................................................................. 59 4.5.6 Denosumab ....................................................................................................................................... 59

4.6 Comparative Heat Map ........................................................................................................................... 60 5 Market Forecasts .................................................................................................................................................... 63

5.1 Asia-Pacific .................................................................................................................................................. 63 5.1.1 Treatment Usage Patterns ............................................................................................................ 63 5.1.2 Market Size ........................................................................................................................................ 64

5.2 India .............................................................................................................................................................. 65 5.2.1 Treatment Usage Patterns ........................................................................................................... 65 5.2.2 Annual Cost of Therapy................................................................................................................. 66 5.2.3 Market Size ........................................................................................................................................ 67

5.3 China ............................................................................................................................................................. 67 5.3.1 Treatment Usage Patterns ............................................................................................................ 67 5.3.2 Annual Cost of Therapy................................................................................................................. 68 5.3.3 Market Size ....................................................................................................................................... 69

5.4 Australia ...................................................................................................................................................... 69 5.4.1 Treatment Usage Patterns ........................................................................................................... 69 5.4.2 Annual Cost of Therapy.................................................................................................................. 70 5.4.3 Market Size ......................................................................................................................................... 71

5.5 Japan ............................................................................................................................................................. 71 5.5.1 Treatment Usage Patterns ............................................................................................................. 71 5.5.2 Annual Cost of Therapy.................................................................................................................. 72 5.5.3 Market Size ........................................................................................................................................ 73



5.6 Drivers and Barriers of Rheumatoid Arthritis Therapeutics Market ............................................ 73 5.6.1 Drivers ................................................................................................................................................. 73 5.6.2 Barriers ................................................................................................................................................ 74

6 Deals .......................................................................................................................................................................... 76 6.1 Licensing Agreements ............................................................................................................................. 76

6.1.1 Deal Values by Therapeutic Molecule Type ............................................................................ 78 6.1.2 Deal Values by Therapeutic Mechanism of Action ............................................................... 80 6.1.3 AstraZeneca Enters into Licensing Agreement with Rigel Pharma for Fostamatinib

Disodium ............................................................................................................................................ 82 6.1.4 Alder Biopharmaceuticals Enters into Licensing Deal with Bristol-Myers Squibb and

Alder Biopharmaceuticals for Clazakizumab .......................................................................... 82 6.1.5 Janssen Biotech Enters into a Licensing Deal with Astellas Pharma for Peficitinib .... 82 6.1.6 Ablynx Enters into a Licensing Deal with AbbVie for the Nanobody ALX-006 ............ 82

6.2 Co-development ........................................................................................................................................ 83 6.2.1 Deal Values by Therapeutic Molecule Type and Phase ....................................................... 84 6.2.2 Deal Values by Therapeutic Mechanism of Action and Phase .......................................... 86 6.2.3 GlaxoSmithKline enters into Global Agreement with Archemix .........................................88 6.2.4 Abbott Laboratories Enters into Global Collaboration with Galapagos for filgotinib ...88 6.2.5 Chroma Therapeutics Enters into a Co-development Agreement with

GlaxoSmithKline ...............................................................................................................................88 7 Appendix .................................................................................................................................................................. 89

7.1 All Pipeline Drugs by Phase of Development .................................................................................. 89 7.1.1 Discovery ........................................................................................................................................... 89 7.1.2 Preclinical .......................................................................................................................................... 90 7.1.3 IND-CTA Filed .................................................................................................................................. 90 7.1.4 Phase I .................................................................................................................................................. 91 7.1.5 Phase II ................................................................................................................................................ 93 7.1.6 Phase III ............................................................................................................................................... 93

7.2 Market Forecasts to 2021 ....................................................................................................................... 94 7.3 Abbreviations ............................................................................................................................................. 97 7.4 Bibliography ............................................................................................................................................... 99

7.4.1 References for Figure 10 .............................................................................................................. 106 7.4.2 References for Figure 26 ............................................................................................................. 108

7.5 Research Methodology ......................................................................................................................... 109 7.5.1 Coverage .......................................................................................................................................... 109 7.5.2 Secondary Research ..................................................................................................................... 109 7.5.3 Primary Research ............................................................................................................................ 110 7.5.4 Therapeutic Landscape ................................................................................................................. 110 7.5.5 Geographical Landscape .............................................................................................................. 112 7.5.6 Pipeline Analysis ............................................................................................................................. 113

7.6 Expert Panel Validation .......................................................................................................................... 113 7.7 Contact Us .................................................................................................................................................. 113 7.8 Disclaimer ................................................................................................................................................... 113



1.1 List of Tables

Table 1: ACR-EULAR Classification Criteria for Rheumatoid Arthritis, 2010 ....................................... 14 Table 2: Rheumatoid Arthritis, Therapeutics, Global, All Pipeline Products, Discovery, 2014 .......... 89 Table 3: Rheumatoid Arthritis, Therapeutics, Global, All Pipeline Products, Preclinical Phase, 2014

...................................................................................................................................................... 90 Table 4: Rheumatoid Arthritis, Therapeutics, Global, All Pipeline Products, IND/CTA-Filed, 2014 .. 91 Table 5: Rheumatoid Arthritis, Therapeutics, Global, All Pipeline Products, Phase I, 2014 ............... 92 Table 6: Rheumatoid Arthritis, Therapeutics, Global, All Pipeline Products, Phase II, 2014 .............. 93 Table 7: Rheumatoid Arthritis, Therapeutics, Global, All Pipeline Products, Phase III, 2014 ............. 94 Table 8: Rheumatoid Arthritis, Therapeutics Market, Asia-Pacific, Market Forecast, 2014–2021 .... 95 Table 9: Rheumatoid Arthritis, Therapeutics Market, India, Market Forecast, 2014–2021 ................ 95 Table 10: Rheumatoid Arthritis, Therapeutics Market, China, Market Forecast, 2014–2021 .............. 96 Table 11: Rheumatoid Arthritis, Therapeutics Market, Australia, Market Forecast, 2014–2021 ......... 96 Table 12: Rheumatoid Arthritis, Therapeutics Market, Japan, Market Forecast, 2014–2021 .............. 96 Table 13: Abbreviations .............................................................................................................................. 97

1.2 List of Figures

Figure 1: American College of Rheumatology Treatment Guidelines, 2012 ........................................ 16 Figure 2: Rheumatoid Arthritis Market, Global, Annual Sales of Remicade ($bn), 2008–2014 .......... 24 Figure 3: Rheumatoid Arthritis Market, Global, Annual Sales of Humira ($bn), 2008–2014 .............. 25 Figure 4: Rheumatoid Arthritis Market, Global, Annual Sales of Enbrel ($bn), 2008–2014 ................ 26 Figure 5: Rheumatoid Arthritis Market, Global, Annual Sales of Rituxan ($bn), 2008–2014 .............. 27 Figure 6: Rheumatoid Arthritis Market, Global, Annual Sales of Orencia ($m), 2008–2014 .............. 29 Figure 7: Rheumatoid Arthritis Market, Global, Annual Sales of Simponi ($m), 2009–2014 .............. 30 Figure 8: Rheumatoid Arthritis Market, Global, Annual Sales of Cimzia ($m), 2008–2014 ................ 31 Figure 9: Rheumatoid Arthritis Market, Global, Annual Sales of Actemra ($m), 2008–2014 .............. 33 Figure 10: Comparative Efficacy and Safety of Marketed Products ........................................................ 35 Figure 11: Rheumatoid Arthritis Market, Global, Pipeline, 2014 .............................................................. 39 Figure 12: Rheumatoid Arthritis Market, Global, Pipeline by Mechanism of Action, 2014 .................... 41 Figure 13: Rheumatoid Arthritis Market, Global, Pipeline, Cytokine Inhibitors, 2014 ............................ 43 Figure 14: Rheumatoid Arthritis Market, Global, Pipeline, Inhibitors of B and T Cells, 2014 ................ 44 Figure 15: Rheumatoid Arthritis Market, Global, Pipeline, Intracellular Kinase Inhibitors, 2014 ........... 45 Figure 16: Rheumatoid Arthritis, Global, Clinical Trial Failure Rate (%), 2006–2014 ............................. 46 Figure 17: Rheumatoid Arthritis, Global, Clinical Trial Failure Rate (%), 2006–2014 ............................. 47 Figure 18: Rheumatoid Arthritis, Global, Clinical Trial Failure Rate (%), 2006–2014 ............................. 48 Figure 19: Rheumatoid Arthritis Market, Global, Pipeline, Clinical Trial Size by Molecule Type by

Product, 2006–2014 .................................................................................................................. 49 Figure 20: Rheumatoid Arthritis Market, Global, Pipeline, Clinical Trial Size by Molecule Type by Trial,

2006–2014.................................................................................................................................. 50 Figure 21: Rheumatoid Arthritis Market, Global, Pipeline, Clinical Trial Size by Mechanism of Action

by Product, 2006–2014 ............................................................................................................. 51 Figure 22: Rheumatoid Arthritis Market, Global, Pipeline, Clinical Trial Size by Mechanism of Action

by Trial, 2006–2014 ................................................................................................................... 52 Figure 23: Rheumatoid Arthritis Market, Global, Pipeline, Clinical Trial Duration by Molecule Type by

Product (months), 2006–2014 .................................................................................................. 53 Figure 24: Rheumatoid Arthritis Market, Global, Pipeline, Clinical Trial Duration by Mechanism of

Action by Product (months), 2006–2014 ................................................................................. 54 Figure 25: Rheumatoid Arthritis Market, Global, Frequency of Primary Endpoints Measured in Clinical

Trials, 2006–2014 ...................................................................................................................... 55 Figure 26: Comparative Efficacy and Safety of Pipeline Programs ......................................................... 62 Figure 27: Rheumatoid Market, Asia-Pacific, Treatment Usage Patterns (million), 2014–2021 ............ 64 Figure 28: Rheumatoid Market, Asia-Pacific, Market Size ($bn), 2014–2021 ......................................... 65 Figure 29: Rheumatoid Market, India, Treatment Usage Patterns (million), 2014–2021 ....................... 66 Figure 30: Rheumatoid Market, India, Annual Cost of Therapy ($), 2014–2021 ..................................... 66 Figure 31: Rheumatoid Market, India, Market Size ($m), 2014–2021 ...................................................... 67



Figure 32: Rheumatoid Market, China, Treatment Usage Patterns (million), 2014–2021 ...................... 68 Figure 33: Rheumatoid Market, China, Annual Cost of Therapy ($), 2014–2021 ................................... 68 Figure 34: Rheumatoid Market, China, Market Size ($m), 2014–2021 .................................................... 69 Figure 35: Rheumatoid Market, Australia, Treatment Usage Patterns (‘000), 2014–2021 .................... 70 Figure 36: Rheumatoid Market, Australia, Annual Cost of Therapy ($), 2014–2021 .............................. 70 Figure 37: Rheumatoid Market, Australia, Market Size ($m), 2014–2021 ............................................... 71 Figure 38: Rheumatoid Market, Japan, Treatment Usage Patterns (‘000), 2014–2021 ........................ 72 Figure 39: Rheumatoid Market, Japan, Annual Cost of Therapy ($), 2014–2021 ................................... 72 Figure 40: Rheumatoid Market, Japan, Market Size ($bn), 2014–2021 .................................................. 73 Figure 41: Rheumatoid Arthritis Market, Global, Licensing Deals, 2006–2014 ..................................... 77 Figure 42: Rheumatoid Arthritis Market, Global, Licensing Deals, 2006–2014 ..................................... 79 Figure 43: Rheumatoid Arthritis Market, Global, Licensing Deals, 2006–2014 ..................................... 81 Figure 44: Rheumatoid Arthritis Market, Global, Co-development Deals, 2006–2014 ......................... 83 Figure 45: Rheumatoid Arthritis Market, Global, Co-development Deals, 2006–2014 ......................... 85 Figure 46: Rheumatoid Arthritis Market, Global, Co-development Deals, 2006–2014 ......................... 87 Figure 47: GBI Research Market Forecasting Model .............................................................................. 112



2 Introduction

2.1 Disease Introduction

Rheumatoid Arthritis (RA) is a chronic, progressive and currently incurable autoimmune disease that primarily affects the joints. It is characterized by synovial inflammation and gradual bone erosion over many years (Lefèvre et al., 2009). Disease progression results in stiffness and pain, especially in the hands and feet, which hinders mobility. Without treatment, the disease leads to joint destruction and disability. RA can have a substantial impact on quality of life and place a considerable economic burden upon the patient.

RA affects approximately XX% of the world’s population. The prevalence rate varies across the globe from XX% to XX%, and is higher in developed countries than in developing nations. However, in both developed and developing countries, prevalence is higher in women than in men (WHO, 2012).

The chronic nature of the disease, which requires ongoing treatment, as well as the large target patient population and the relatively high Annual Cost of Therapy (ACoT), has made RA treatment a highly lucrative market. In addition, the signaling pathways targeted by the currently marketed products are relevant to many other autoimmune and oncological diseases and thus allow for significant repositioning opportunities.

The therapeutic options for the treatment of RA have grown rapidly over the past two decades. Significant advances in disease understanding and the identification of novel molecular targets have opened up avenues for new drug developments and resulted in sustained interest and high R&D activity. In particular, the diversification in pharmaceutical therapeutics has led to a transformation in both the clinical and commercial landscape with the advent of monoclonal antibodies (mAb). The first biologic to be approved for RA was Enbrel (etanercept), in 1998. Since then, multiple biological therapies, including mAbs, biosimilars and therapeutic proteins, have been approved across the global market, resulting in one of the highest rates of penetration of any indication. In 2013, three Tumor Necrosis Factor Alpha (TNF-α)-targeting mAbs, Humira (adalimumab), Remicade (infliximab) and Enbrel (etanercept), all of which are approved for RA treatment and many other indications, were ranked among the top-XX best-selling drugs in the world with global revenues of $XX billion, $XX billion and $XX billion respectively.

The RA therapeutic market has become very competitive due to the high number of new drug approvals. Competition is fierce, particularly among TNF-α inhibitors, which dominate the treatment market for RA patients who are refractory to traditional Disease-Modifying Anti-rheumatic Drugs (DMARD). Despite this, XX% of RA patients fail to attain a clinical response when treated with TNF-α inhibitors (Rubbert-Roth and Finckh, 2009). However, other targeted programs, as well as newly marketed small-molecule DMARDs such as Janus Kinase (JAK) inhibitors, have the potential to replace inefficacious TNF-α inhibitors.

Despite the superior efficacy of recently marketed therapies over traditional DMARD therapies, there is a need to improve safety in the therapeutic landscape. Elevated rates of infection are a frequent consequence of the immunosuppression involved in treatments, but this is required to suppress the autoimmune responses responsible for the symptoms of the condition. As a result, these biological therapies are not recommended to patients who are susceptible to infection. In addition, there is a need to create biologics with a more convenient and less invasive drug-delivery method than existing ones, all of which are administered subcutaneously or intravenously. These routes of administration are frequently associated with pain, rash, and allergic reactions at the injection or infusion site, and, in the case of infusion, flu-like illness, fever, chills, nausea, and headache. Thus, convenient and safe routes of administration without significant compromise of therapy efficacy remain unmet needs. However, the Food and Drug Administration (FDA) has approved Xeljanz (tofacitinib), an orally administered small-molecule drug, as a second-line treatment for RA patients who have not shown an adequate response to Methotrexate (MTX) and as a third-line therapy for patients who have not responded sufficiently to biologics. Thus, Xeljanz addresses the need for a safer and more convenient method of drug delivery.



2.8 Disease Progression

Without therapeutic intervention, disease progression will result in the worsening of symptoms, extensive structural damage of the joint and, ultimately, disability. The progression of the disease is typically classified into four stages:

Stage I: In stage I RA, the synovium begins to swell, causing pain, stiffness and redness in the surrounding area. At this stage, there is no evidence by X-ray diagnosis that bone damage has occurred.

2.9 Pharmacotherapy Algorithm

The current therapies for RA are not curative. Nonetheless, therapeutic goals include preservation of joint function and quality of life, minimization of pain and inflammation, and control of systemic complications. Small-molecule DMARD and anti-inflammatory drugs, such as Non-Steroidal Anti-Inflammatory Drugs (NSAID) and glucocorticoids, remain first-line therapy for patients with early-stage RA (Figure 1). Historically, rheumatologists would prescribe low doses of DMARDs, gradually escalating the dosage. Sequential monotherapy or step-up combination-therapy treatment strategies were favored, involving the substitution and addition, respectively, of another DMARD, if a suboptimal response was achieved in response to the first DMARD.



In November 2012, the US FDA approved Xeljanz (tofacitinib) as an alternative second-line treatment for adult patients with moderate-to-severe active RA who have not shown an adequate response or are intolerant to MTX, or as a third-line therapy for patients who have not responded sufficiently to biologics. Xeljanz is an oral non-biologic DMARD that targets JAK and can be used as a monotherapy or in combination with MTX or other non-biologic DMARDs.

Figure 1: American College of Rheumatology Treatment Guidelines, 2012

DMARD monotherapy

Combination DMARD therapy (double or triple

therapy)

Target: low

disease activity or remission

Features of poor

prognosis

Anti-TNFα with or without MTX

orcombination DMARD therapy (double or

triple therapy)

DMARD monotherapy

orMTX and HCQ

Disease activity

Features of poor

prognosis

HighLow

Present

AbsentPresent

Absent

Source: Singh et al., 2012

DMARD: Disease-Modifying Anti-Rheumatic Drugs; HCQ: Hydroxychloroquine; MTX: Methotrexate; TNF: Tumor Necrosis Factor

2.10 Treatment Options

Although biological drugs such as Remicade (infliximab), Humira (adalimumab) and Enbrel (etanercept) represented some of the most commercially successful therapies in 2013, they are set against a background of a variety of other treatment options that have a long history of usage. mAbs have been in use for RA treatment since 1998, largely as second-line therapies for patients resistant to MTX and other first-line DMARDs. This may be due to the risk of serious adverse effects attached to biologics for RA, but it could also be due to the high relative cost of biologics.



3 Marketed Products

3.1 Overview

As shown in the treatment algorithm, symptomatic and small-molecule disease-modifying drugs usually represent first-line therapies for patients with mild-to-moderate RA, while most biologic drugs, especially TNF-α inhibitors, are reserved for those who are refractory to first-line treatments. However, Xeljanz and other biologics can also cater for patients who are refractory or unsuitable for second-line TNF-α inhibitors, thus straddling second-line and third-line therapies.

3.2 Small-Molecule Disease-Modifying Anti-rheumatic Drugs

3.2.1 Methotrexate-Based Products

MTX is a small-molecule immunosuppressant derived from aminopterin, a folic-acid-analogue-based cytotoxic drug that was first reported to enhance overall survival in acute leukemia in children. It was then reported that aminopterin contributed to disease remission in patients with RA when administered in conjunction with corticosteroids (Gubner et al., 1951). What began as a drug for the treatment of cancer, particularly childhood leukemia, is now used to treat a wide variety of immunologic disorders. The use of MTX in the treatment of RA dates from the 1960s. It is currently used as a first-line DMARD for patients. Many physicians use MTX for its steroid-sparing properties in patients with asthma and patients who have side effects related to corticosteroid use.



4 Product Pipeline

4.1 Overview

Treatment algorithms for moderate-to-severe RA have been greatly diversified due to the emergence of efficacious biologics as a new class of therapy. The current market is now densely populated with targeted therapies that all compete for the same sub-population of RA patients, namely those who are refractory to first-line DMARDs such as MTX.

However, in spite of the developments in recent years, there remains a significant unmet need in terms of drug profiles safety and RoA convenience. Systemic therapies such as biologic drugs are often administered via IV infusion or subcutaneous injection, which is likely to cause inconvenience and a level of discomfort.



4.4.1 Overall Attrition Rate

Of the XX clinical trials conducted since 2006, the clinical trial failure rates were XX%, XX%, XX%for Phases I, II, and III respectively (Figure 16). The overall attrition rate for products in development to treat RA was XX%.. It is noteworthy that there are nearly twice as many Phase II trials as Phase I trials. This suggests there are more studies conducted per pipeline drug than in Phase I. There are fewer Phase III trials (XX) than Phase II trials presumably due to the attrition rates in Phase II and fewer trials per molecule.

Figure 16: Rheumatoid Arthritis, Global, Clinical Trial Failure Rate (%), 2006–2014

Phase I Phase II Phase III Attrition rate

Fa

ilure

rate

(%)

n=XX

n=XX

n=XX

n=XX

Source: GBI Research, Proprietary Clinical Trials Database

4.4.2 Attrition Rate by Phase, Molecule Type and Target

Overall, the average clinical trial failure rate of biologics, mAbs in particular, is lower than that of small molecules (Figure 17A). This is particularly evident in Phase III, which has no record of mAbs that have failed to meet clinical trial endpoints (Figure 17.D). This is largely due to the potent ability of these mAbs to elicit substantial response and achieve primary endpoints such as ACR20, AC50 or ACR70 in patients, especially those who are refractory to MTX or first-line DMARDs.

Overall, the average clinical trial failure rate of biologics, in particular, mAbs, is lower than that of small molecules.



5 Market Forecasts

5.1 Asia-Pacific

The following section provides a multi-scenario forecast over the 2014–2021 period for the RA therapeutics market in India, China, Australia and Japan. For each of these markets, projections are presented for prevalence and treatment populations, ACoT per patient, and total market size. The market projections incorporate multiple variances to account for uncertainty in factors such as inflation rates, year of new drug approval, and the changing balance of market share between emerging and current therapeutics.

5.1.1 Treatment Usage Patterns

RA prevalence varies considerably across the four APAC territories, ranging from XX% in Australia to XX% in China in 2014. The total prevalence population is forecast to grow from XX million in 2014 to over XX million in 2021 (Figure 27). Although prevalence is low in India and China, they account for large shares of the patient pool due to their high population densities. However, their treatment populations are small due to low awareness, which reduces the likelihood of achieving an appropriate RA diagnosis, and a lack of healthcare facilities, especially in rural areas where prevalence is estimated to be higher. The total treatment population is expected to grow from XX million to XX million in the forecast period.

The late-stage programs are likely to be positioned as second-line treatments.



Figure 27: Rheumatoid Market, Asia-Pacific, Treatment Usage Patterns (million), 2014–2021

2014 2015 2016 2017 2018 2019 2020 2021

Po

pu

latio

n (m

illio

n)

Prevalence population Treatment population

Source: GBI Research, Proprietary Clinical Trial Database

5.1.2 Market Size

GBI Research estimates that the RA therapeutics market across the four APAC territories was worth $XX billion in 2014, and expects it to grow at a Compound Annual Growth Rate (CAGR) of XX% to $XX billion in 2021. In a best-case scenario, it will grow at a CAGR of XX% to $XX billion by the end of 2021, while in a worst-case scenario, it will grow at a CAGR of XX% to $XX billion.



6.1.1 Deal Values by Therapeutic Molecule Type

Of the XX licensed therapies for which the molecule type has been disclosed, more involve biologics than small molecules (XX and XX respectively), distributed across most pipeline stages (Figure 42A). However, aggregate deal values were similar, with small molecules and biologic products valued cumulatively at $XX billion and $XX billion respectively (Figure 42B). This suggests that, on average, individual small-molecule therapies were more highly valued than biologics. However, the sample size of disclosed total deal values for RA therapeutics is small. A relatively high population of therapies were licensed in Phase II (Figure 42B and 43C), where it seems that small molecules fetch a wider range of valuations than biologics.

Overall, despite the profound clinical and commercial impact of mAbs in RA over the last decade, Figure 42 suggests that, in the RA licensing landscape, biologics have not generated higher licensing deal values. This implies that acquiring companies do not attach a high commercial value to these molecule types in comparison with small-molecule therapeutics. However, the strength of this conclusion is limited by the small number of disclosed deal values available.



Figure 42: Rheumatoid Arthritis Market, Global, Licensing Deals, 2006–2014

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Source: GBI Research, Proprietary Strategic Alliances Database

mAb: monoclonal Antibody



7 Appendix

7.1 All Pipeline Drugs by Phase of Development

7.1.1 Discovery

Table 2: Rheumatoid Arthritis, Therapeutics, Global, All Pipeline Products, Discovery, 2014

Product name Company Molecule type Mechanism of action

Source: GBI Research, Proprietary Pipeline Products Database



7.1.2 Preclinical

Table 3: Rheumatoid Arthritis, Therapeutics, Global, All Pipeline Products, Preclinical Phase, 2014





7.1.3 IND-CTA Filed

Table 4: Rheumatoid Arthritis, Therapeutics, Global, All Pipeline Products, IND/CTA-Filed, 2014





7.1.4 Phase I

Table 5: Rheumatoid Arthritis, Therapeutics, Global, All Pipeline Products, Phase I, 2014





7.1.5 Phase II

Table 6: Rheumatoid Arthritis, Therapeutics, Global, All Pipeline Products, Phase II, 2014





7.1.6 Phase III

Table 7: Rheumatoid Arthritis, Therapeutics, Global, All Pipeline Products, Phase III, 2014





7.2 Market Forecasts to 2021

Table 8: Rheumatoid Arthritis, Therapeutics Market, Asia-Pacific, Market Forecast, 2014–2021

2014 2015 2016 2017 2018 2019 2020 2021

Prevalence population ('000)

Treatment population ('000)

Maximum market size ($bn)

Projected market size ($bn)

Minimum market size ($bn)

Source: GBI Research

Table 9: Rheumatoid Arthritis, Therapeutics Market, India, Market Forecast, 2014–2021 2014 2015 2016 2017 2018 2019 2020 2021



Maximum market size ($m)

Projected market size ($m)

Minimum market size ($m)




Table 10: Rheumatoid Arthritis, Therapeutics Market, China, Market Forecast, 2014–2021 2014 2015 2016 2017 2018 2019 2020 2021







Table 11: Rheumatoid Arthritis, Therapeutics Market, Australia, Market Forecast, 2014–2021 2014 2015 2016 2017 2018 2019 2020 2021







Table 12: Rheumatoid Arthritis, Therapeutics Market, Japan, Market Forecast, 2014–2021 2014 2015 2016 2017 2018 2019 2020 2021









7.3 Abbreviations

Table 13: Abbreviations

Abbreviation Expanded term

A3AR A3 Adenosine Receptor

ABS Australian Bureau of Statistics

ACPA Anti-Citrullinated Protein Antibody

ACR American College of Rheumatology

ACoT Annual Cost of Therapy

AP-1 Activator Protein-1

APAC Asia-Pacific

API Active Pharmaceutical Ingredient

ASP Average Selling Price

CAGR Compound Annual Growth Rate

CC Chemokine

CCR Chemokine Receptor

CD Cluster of Differentiation

COX-2 Cyclooxygenase-2

CHMP Committee for Medicinal Products for Human Use

CRP C-Reactive Protein

CTA Clinical Trial Authorization

DAS-28 Disease Activity Score-28

DC Dendritic Cell

DMARD Disease-Modifying Anti-Rheumatic Drug

EMA European Medicines Agency

ESR Erythrocyte Sedimentation Rate

EULAR European League Against Rheumatism

fab fragment antigen-binding

Fc crystallizable Fragment

FDA Food and Drug Administration

GM-CSF Granulocyte-Macrophage Colony-Stimulating Factor

GPCR G Protein Coupled Receptor

HAQ Health Assessment Questionnaire

HCQ Hydroxychloroquine

HDL High-Density Lipoprotein

ICAM-1 Intercellular Adhesion Molecule-1

Ig Immunoglobulin

IL Interleukin

IL-1Ra Interleukin-1 Receptor a

IL-6R IL-6 Receptor

IND Investigational New Drug

IV Intravenous

JAK Janus Kinase



JNK c-Jun N-Terminal Kinase

LDL Low-Density Lipoprotein

LEF Leflunomide

mAb monoclonal Antibody

MAPK Mitogen-Activated Protein Kinase

MCSF Macrophage Colony Stimulating Factor

MoA Mechanism of Action

MSC Mesenchymal Stem Cell

MTX Methotrexate

mTSS Modified Total Sharp Score

NFκB Nuclear Factor kappa-B

NHS National Health Service

NICE National Institute of Clinical Excellence

NOD Non-Obese Diabetic

NSAID Non-Steroidal Anti-Inflammatory Drug

PAD Peptidylarginine Deiminase

PBS Pharmaceutical Benefits Scheme

RA Rheumatoid Arthritis

RANKL Receptor Activator of Nuclear factor Kappa-B Ligand

RASS Rheumatoid Arthritis Severity Scale

RF Rheumatoid Factor

RoA Route of Administration

STAT Signal Transducers and Activators of Transcription

Th T helper

TLR Toll-Like Receptor

TNFR TNF Receptor

TB Tuberculosis

TNF-α Tumor Necrosis Factor Alpha

TWEAK Tumor necrosis factor-like WEAK inducer of apoptosis

Treg regulatory T




7.4 Bibliography

ABS (2012). Arthritis and Osteoporosis. Australian Bureau of Statistics. Available from: http://www.abs.gov.au/ausstats/[email protected]/Lookup/4364.0.55.001chapter3102011-12 [Accessed on February 22, 2015]

ACR (2014). 2010 Rheumatoid Arthritis Classification. American College of Rheumatology. https://www.rheumatology.org/practice/clinical/classification/ra/ra_2010.asp [Accessed on January 28, 2015]

AIHW (2013). A snapshot of rheumatoid arthritis. Australian Institute of Health and Welfare; Bulletin 116. Available from: http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=60129543377

Amacher DE (1998). Serum transaminase elevations as indicators of hepatic injury following the administration of drugs. Regulatory Toxicology and Pharmacology; 27(2): 119–130

Arnett FC, et al. (1988). The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheumatology; 31(3): 315–324

Bathon JM, et al. (2000). A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. The New England Journal of Medicine; 343(22): 1586–1593

Beckmann PM, et al. (1990). Tumor Necrosis Factor-alpha and -beta Receptors. European Patent Office. Available from: https://register.epo.org/espacenet/application?number=EP90309875 [Accessed on January 10, 2015]

Berger CT, et al. (2009). A patient’s wish: anakinra in pregnancy. Annals of the Rheumatic Diseases; 68(11): 1794–1795

Biver E, et al. (2009). Low and stable prevalence of rheumatoid arthritis in northern France. Joint Bone Spine; 76(5); 497–500

Boross P and Leusen JH (2012). Mechanisms of action of CD20 antibodies. American Journal of Cancer; 2(6): 676–690

Boyle P, et al. (1994). Anti-TNF alpha human monoclonal antibodies. European Patent Office. Available from: https://register.epo.org/espacenet/application; jsessionid=05A8A57B1CF01864A8F88AFFED16F0E3.RegisterPlus_prod_1?number=EP94102560&tab=main [Accessed February 10, 2015]

Breedveld FC and Combe B (2011). Understanding emerging treatment paradigms in rheumatoid arthritis. Arthritis Research and Therapy; 13(Suppl 1): S3

Brennan FM, et al. (2008). Evidence that cytokines play a role in rheumatoid arthritis. Journal of Clinical Investigation. 118(11):3537–45

BMS (2013). Bristol-Myers Squibb Reports Fourth Quarter and Full Year 2013 Financial Results. Bristol-Myers Squibb. Available from: http: //news.bms.com/press-release/financial-news/bristol-myers-squibb-reports-fourth-quarter-and-full-year-2013-financia [Accessed February 18, 2015]

Brockhaus M, et al. (1995). Human TNF receptor fusion protein. US Patent and Trademark Office. Available from: http: //patft.uspto.gov/netacgi/nph-Parser?Sect2=PTO1&Sect2=HITOFF&p=1&u=/netahtml/PTO/search-bool.html&r=1&f=G&l=50&d=PALL&RefSrch=yes&Query=PN/8063182 [Accessed March 10, 2015]

Burmester GR, et al. (2013). Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet; 381(9865): 451–460

Burmester GR, et al. (2014). A randomised, double-blind, parallel-group study of the safety and efficacy of subcutaneous tocilizumab versus IV tocilizumab in combination with traditional disease-modifying antirheumatic drugs in patients with moderate to severe rheumatoid arthritis (SUMMACTA study). Annals of the Rheumatic Diseases; 73(1): 69–74



PRNewswire (2011). New Sirukumab (CNTO 136) Phase 2 Data Show Efficacy of Interleukin-6 Inhibitor Across Multiple Dose Regimens in Treatment of Rheumatoid Arthritis. PRNewswire. Available from: http: //www.prnewswire.com/news-releases/new-sirukumab-cnto-136-phase-2-data-show-efficacy-of-interleukin-6-inhibitor-across-multiple-dose-regimens-in-treatment-of-rheumatoid-arthritis-133351453.html [Accessed on December 15, 2014]

Regeneron (2013). Sanofi and Regeneron Report Positive Results with Sarilumab in First Phase 3 Rheumatoid Arthritis Registration Trial. Regeneron. Available from: http: //investor.regeneron.com/releasedetail.cfm?ReleaseID=809088 [December 15, 2014]

Tak PP, et al. (2011). Chemokine receptor CCR1 antagonist CCX354-C treatment for rheumatoid arthritis: CARAT-2, a randomised, placebo controlled clinical trial. Annals of the Rheumatic Diseases; 72(3): 337–344

Tigenix (2014). Cx611. Tigenix. Available from: http: //www.tigenix.com/en/page/15/cx611 [Accessed on March 15, 2015]

Vertex. (2011). Phase 2 Data for Selective Oral JAK3 Inhibitor VX-509 Show Significant Improvements in Signs and Symptoms of Rheumatoid Arthritis. Vertex. Available from: http: //investors.vrtx.com/releasedetail.cfm?ReleaseID=621143 [Accessed on December 15, 2014]

7.5 Research Methodology

GBI Research’s dedicated research and analysis teams consist of experienced professionals with advanced statistical expertise and marketing and 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 of GBI Research’s databases are continuously updated and revised. The following research methodology is followed for all databases and reports.

7.5.1 Coverage

The objective of updating GBI Research’s 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.

7.5.2 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

7.5.3 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 medical equipment markets

Key opinion leaders: physicians and surgeons that specialize in the therapeutic areas in which specific medical equipment is used

7.5.4 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 dosing 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 that 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.



7.5.4.1 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 47: GBI Research Market Forecasting Model


The preceding 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.

7.5.5 Geographical Landscape

GBI Research analyzes four major geographies: Australia, India, China 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. 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.



7.5.6 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.

7.6 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.

7.7 Contact Us

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

North America: +1 646 395 5477

Europe: +44 207 406 6777

Asia-Pacific: +91 40 6616 6878

E-mail: [email protected]

7.8 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.

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