japan drug forecast and market analysis to 2022 …5.4.5 the impact of biosimilars will be felt...

REFERENCE CODE GDHC210CFR | PUBLICAT ION DATE JANUARY 2014

CROHN’S DISEASE – JAPAN DRUG FORECAST AND MARKET ANALYSIS

TO 2022

Crohn’s Disease – Japan Drug Forecast and Market Analysis to 2022 2 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.

CROHN’S DISEASE – JAPAN DRUG FORECAST AND MARKET ANALYSIS TO 2022

Executive Summary

The below mentioned table presents the key

metrics for Crohn’s disease (CD) in Japan:

Crohn’s Disease: Key Metrics in the Japan Markets

2012 Market Sales

Anti-TNF $216.0m

Aminosalicylates $11.9m

Total $227.8m

Key Events (2012–2022) Type of Impact

Approval and launch of J&J’s Stelara: 2016

AbbVie’s Humira patent expiry: 2017

Adalimumab biosimilars launch: 2017

Approval and launch of Takeda’s Entyvio: 2019

J&J’s Remicade patent expiry: 2021

Infliximab biosimilars launch: 2021

2022 Market Sales

Anti-TNF $201.9m

Integrin inhibitors $17.2m

Anti-IL $13.3m

Biosimilars $45.1m

5-ASAs $10.7m

Total $288.2m Source: GlobalData

Sales for CD in Japan in 2012–2022:

The Japan CD market was worth approximately

$227.8 million in 2012, with a projected compound

annual growth rate (CAGR) of 2.4% due to an

increase in total sales to $288.2 million in 2022.

Major growth drivers in the Japan CD market over

the forecast period include:

Increasing number of prevalent cases of CD

Continued uptake of TNF inhibitors, particularly

Remicade

Launch of the first non-anti-TNFs during the

mid- to late forecast

Well-developed universal healthcare system

ensures insurance coverage for patients with

chronic diseases

Conversely, major barriers to the growth of the CD

market include:

Biennial pricing system may limit long-term

revenues for companies operating in this

market.

Time lag between drug approval and launch,

due to the process required for listing a drug

on the National Health Insurance (NHI)

Regulatory approval is often contingent upon

companies presenting domestic and/or

Japanese-specific clinical trial data.



Executive Summary

Below mentioned figure illustrates the sales for CD

in Japan by therapeutic class during the 10-year

forecast period.

CD: Sales of Japan by Therapeutic Class, 2012–2022

95%

5% 2012Total: $227.8m

Anti-TNF

Aminosalicylates

70%

6%

4%

16%4%

2022Total: $288.2m

Anti-TNF

Integrin inhibitors

Anti-IL

Biosimilars

5-ASAs Source: GlobalData

What Do Physicians Think?

Following the approval of Hospira/Celltrion’s

Inflectra, a biosimilar of the market-leading

biologic, Remicade, in September 2013 for the

multiple autoimmune indications for which

Remicade is approved, some KOLs highlighted

that they would await data from a CD- or an IBD-

specific trial before prescribing Inflectra for their

CD or UC patients. This, in turn, could limit the

initial uptake of Inflectra.

“I am not interested in [using] Inflectra in [my] IBD

[patients] unless it is tested in IBD[-specific] clinical

trials.”

[EU] key opinion leader

KOLs stressed that predicting the course of CD

remains the most challenging aspect of managing

their CD patients.

“I think the most challenging aspect is to, first of all,

risk-stratify as to what patients are going to do

badly in the long run, and trying to tailor an

effective therapy for them.”

[Outside-US] key opinion leader

Having biomarkers included in their diagnostic

tools is important to gastroenterologists, as it could

allow them to effectively predict the course of CD

in a given patient and allow them to offer a

personalized treatment approach.

“I think we need a more biomarker-based

approach….I think we are falsely diagnosing early

disease. With Crohn’s, two days of endoscopic

techniques and two days of radiological

assessments are precise enough to allow you to

see the morphological damage, but in pre-stage

patients at risk of developing the disease, we do

have difficulties in properly assessing the disease.”




Executive Summary

KOLs stressed their desire for new drug therapies

to treat the anti-TNF refractory patient segment.

“We are learning that the anti-TNF therapies have

a limited lifespan….We are going to run into a

problem where we have a lot of people losing

response to anti-TNF therapy early on in their

disease course, and then they don’t have an option

later on.”

[US] key opinion leader

“All these drugs [anti-TNFs] have a finite natural

history, as we rapidly move from one drug to

another, and five years down the road, someone

with a history of Crohn’s is going to be with no

treatment options.”

[US] key opinion leader

KOLs validated that emerging therapies with novel

MOAs will form the basis of their treatment

paradigm.

“In the future, what we will do is either switching of

anti-TNF therapies, or we will switch to alternative

mechanisms, and we will soon have [the]

alpha4beta7, vedolizumab.”


According to KOLs, anti-IL-6 therapies, which are

currently in early clinical development, hold

promise.

“There are so many companies out there with anti-

IL-6 agents that I feel there could be a new

paradigm coming up, which could add to the value

of innovation…not just to the molecule, but also to

the way we use it.”




Table of Contents

1 Table of Contents

1 Table of Contents ........................................................................................................................ 5

1.1 List of Tables ....................................................................................................................... 9

1.2 List of Figures .................................................................................................................... 11

2 Introduction ................................................................................................................................ 12

2.1 Catalyst .............................................................................................................................. 12

2.2 Related Reports ................................................................................................................. 13

2.3 Upcoming Related Reports ................................................................................................ 14

3 Disease Overview ...................................................................................................................... 15

3.1 Etiology and Pathophysiology ............................................................................................ 15

3.1.1 Etiology .......................................................................................................................... 15

3.1.2 Pathophysiology ............................................................................................................. 15

3.2 Symptoms .......................................................................................................................... 19

3.3 Prognosis ........................................................................................................................... 20

3.4 Quality of Life ..................................................................................................................... 21

4 Disease Management ................................................................................................................ 22

4.1 Treatment Overview ........................................................................................................... 23

4.2 Japan ................................................................................................................................. 28

4.2.1 Diagnosis ....................................................................................................................... 28

4.2.2 Clinical Practice .............................................................................................................. 28

5 Competitive Assessment ........................................................................................................... 30

5.1 Overview ............................................................................................................................ 30

5.2 Strategic Competitor Assessment ...................................................................................... 31

5.3 Product Profiles – Major Brands ........................................................................................ 32

5.3.1 Remicade (infliximab) ..................................................................................................... 32

5.3.2 Humira (adalimumab) ..................................................................................................... 38



Table of Contents

5.3.3 Other Marketed Products ............................................................................................... 42

5.4 Biosimilars ......................................................................................................................... 43

5.4.1 Introduction .................................................................................................................... 43

5.4.2 Hospira’s Inflectra Versus J&J’s Remicade in Key Autoimmune Diseases ..................... 44

5.4.3 Biosimilars in the Immunology Community ..................................................................... 45

5.4.4 By the Numbers: Biosimilars in Development ................................................................. 45

5.4.5 The Impact of Biosimilars Will be Felt Through out the Pharmaceutical Industry ............ 47

6 Opportunity and Unmet Need .................................................................................................... 49

6.1 Overview ............................................................................................................................ 49

6.2 Physicians Desire Biomarkers That Will Allow a Personalized Treatment Approach .......... 50

6.3 More Therapies for Anti-TNF-Refractory Patients .............................................................. 51

6.4 Unmet Needs Gap Analysis ............................................................................................... 52

6.5 Targeted Therapies ............................................................................................................ 53

6.6 Predictive Tools for Early Diagnosis and Treatment ........................................................... 54

7 Pipeline Assessment.................................................................................................................. 55

7.1 Overview ............................................................................................................................ 55

7.2 Promising Drugs in Clinical Development ........................................................................... 55

7.2.1 Entyvio (vedolizumab) .................................................................................................... 57

7.2.2 Stelara (ustekinumab) .................................................................................................... 69

7.3 Other Late-Stage Pipeline Products ................................................................................... 76

7.3.1 Cx601............................................................................................................................. 76

7.3.2 RHB-104 (clarithromycin + clofazimine + rifabutin) ......................................................... 78

8 Market Outlook .......................................................................................................................... 83

8.1 Global Markets ................................................................................................................... 83

8.1.1 Drivers and Barriers – Global Issues .............................................................................. 83



Table of Contents

9 Japan ......................................................................................................................................... 88

9.1 Forecast ............................................................................................................................. 88

9.2 Key Events ......................................................................................................................... 90

9.3 Drivers and Barriers ........................................................................................................... 91

9.3.1 Driver: Pathways for biosimilar approval are already in place ......................................... 91

9.3.2 Driver: Increasing number of prevalent cases of CD....................................................... 91

9.3.3 Driver: Continued uptake of TNF inhibitors, particularly Remicade ................................. 92

9.3.4 Driver: Launch of the first non-anti-TNF during the mid-forecast..................................... 92

9.3.5 Driver: The well-developed universal healthcare system ensures insurance coverage for

patients with chronic diseases ....................................................................................... 93

9.3.6 Barrier: Biennial pricing system may limit long-term revenues for companies operating in

this market ..................................................................................................................... 93

9.3.7 Barrier: Time lag between drug approval and launch, due to the process required for

listing a drug on the NHI ................................................................................................ 93

9.3.8 Barrier: Regulatory approval is often contingent upon companies presenting domestic

and/or Japanese-specific clinical trial data ..................................................................... 94

10 Appendix.................................................................................................................................... 95

10.1 Bibliography ....................................................................................................................... 95

10.2 Abbreviations ................................................................................................................... 100

10.3 Methodology .................................................................................................................... 104

10.4 Forecasting Methodology ................................................................................................. 104

10.4.1 Diagnosed CD Patients ................................................................................................ 104

10.4.2 Percent Drug-Treated Patients ..................................................................................... 105

10.4.3 Drugs Included in Each Therapeutic Class ................................................................... 105

10.4.4 Launch and Patent Expiry Dates .................................................................................. 105



Table of Contents

10.4.5 General Pricing Assumptions ....................................................................................... 106

10.4.6 Individual Drug Assumptions ........................................................................................ 107

10.4.7 Generic Erosion ........................................................................................................... 109

10.4.8 Pricing of Pipeline agents ............................................................................................. 109

10.5 Physicians and Specialists Included in This Study ........................................................... 110

10.6 Primary Research – Prescriber Survey ............................................................................ 112

10.7 About the Authors ............................................................................................................ 113

10.7.1 Author/Reviewer ........................................................................................................... 113

10.7.2 Global Head of Healthcare ........................................................................................... 113

10.8 About GlobalData ............................................................................................................. 114

10.9 Disclaimer ........................................................................................................................ 114



Table of Contents

1.1 List of Tables

Table 1: Symptoms of CD ................................................................................................................................ 20

Table 2: Treatment Guidelines for CD .............................................................................................................. 24

Table 3: Most Commonly Prescribed Drugs for CD in the Global Markets by Disease Severity, 2013 ............... 26

Table 4: Leading Branded Drugs Used to Treat CD ......................................................................................... 32

Table 5: Product Profile – Remicade ................................................................................................................ 34

Table 6: Remicade SWOT Analysis, 2013 ....................................................................................................... 37

Table 7: Product Profile – Humira .................................................................................................................... 39

Table 8: Humira SWOT Analysis, 2013 ............................................................................................................ 42

Table 9: Summary of the Minor Therapeutic Classes in CD, 2013 .................................................................... 43

Table 10: Biosimilars Pipeline, 2013 ................................................................................................................ 46

Table 11: Overall Unmet Needs in CD – Current Level of Attainment ............................................................... 50

Table 12: Clinical Unmet Needs in CD – Gap Analysis, 2013 ........................................................................... 53

Table 13: Promising Drugs in Clinical Development for CD – Pipeline Phase, 2013.......................................... 56

Table 14: Comparison of Therapeutic Classes in Development for CD, 2013 ................................................... 57

Table 15: Product Profile – Entyvio .................................................................................................................. 59

Table 16: Efficacy of Entyvio in GEMINI II Studies of CD ................................................................................. 60

Table 17: Entyvio SWOT Analysis, 2013 .......................................................................................................... 68

Table 18: Product Profile – Stelara .................................................................................................................. 70

Table 19: Comparison of Stelara’s Phase IIb CERTIFI trial Efficacy Data Versus Tysabri’s Phase III Efficacy

Data in Anti-TNF Refractory CD Patients ....................................................................................... 72

Table 20: Stelara SWOT Analysis, 2013 .......................................................................................................... 75

Table 21: Product Profile – Cx601 ................................................................................................................... 77

Table 22: Cx601 SWOT Analysis, 2013 ........................................................................................................... 78



Table of Contents

Table 23: Product Profile – RHB-104 ............................................................................................................... 80

Table 24: RHB-104 SWOT Analysis, 2013 ....................................................................................................... 82

Table 25: Global CD Market – Drivers and Barriers, 2012–2022 ...................................................................... 83

Table 26: Sales Forecasts ($) for CD in Japan, 2012–2022.............................................................................. 89

Table 27: Key Events Impacting Sales for CD in Japan, 2012–2022 ................................................................ 90

Table 28: CD Market in Japan – Drivers and Barriers, 2012–2022 ................................................................... 91

Table 29: Key Launch Dates .......................................................................................................................... 105

Table 30: Key Patent Expiries ........................................................................................................................ 106

Table 31: Physicians Surveyed, By Country ................................................................................................... 112



Table of Contents

1.2 List of Figures

Figure 1: Mucosa of the Bowel in a Healthy Individual (Left) and a Patient With CD (Right) .............................. 16

Figure 2: Potential Biologic Drug Targets for CD .............................................................................................. 19

Figure 3: Patient Care Path for CD .................................................................................................................. 25

Figure 4: Competitive Assessment of Late-Stage Pipeline Agents in CD, 2012–2022 ....................................... 56

Figure 5: Sales for CD in Japan by Drug Class, 2012–2022 ............................................................................. 90



Introduction

2 Introduction

2.1 Catalyst

The Crohn’s disease (CD) market is currently very dynamic, with novel biologic therapies on the

horizon, such as:

Takeda’s alpha4beta7 inhibitor, Entyvio (vedolizumab)

Johnson & Johnson’s (J&J’s) interleukin (IL)-12/23 inhibitor, Stelara (ustekinumab)

These compounds will challenge the current biologics in an attempt to dislodge the stronghold of

the TNF inhibitors, as they aim to tap into the lucrative portion of the CD therapeutics market. If

their promising safety and efficacy profiles translate to clinical practice once they enter the market,

their launch will be to the detriment of the existing market leaders, Remicade (infliximab) and

Humira (adalimumab).

The loss of patent protection of the anti-TNF marketed brands will allow for the emergence of

biosimilars, such as Hospira’s Inflectra (infliximab) a Remicade biosimilar. Patent expiries begin in

2015 for the current market leaders:

J&J’s Remicade

AbbVie’s Humira

Focusing on country dynamics, Canada and the emerging markets of China and India will also play

a key role in driving growth in the long term, with each market forecast to post positive Compound

Annual Growth Rates (CAGRs) from 2012 to 2022, primarily due to the anticipated strong uptake of

Remicade over the forecast period.

Exciting times lay ahead for the CD market place, as the market events noted above are due to

occur against the backdrop of a steadily rising global CD prevalent population. With the clinical

unmet need for better diagnostic tools and treatment options for the anti-TNF-refractory population,

CD represents an attractive autoimmune disease for drug developers. This, in turn should fuel

commercial interest in this subtype of IBD.



Introduction

2.2 Related Reports

GlobalData (2013). PharmaPoint: Psoriasis – Global Drug Forecast and Market Analysis to

2022, May 2013, GDHC48PIDR

GlobalData (2013). PharmaPoint: Rheumatoid Arthritis – Global Drug Forecast and Market

Analysis Event-Driven Update, July 2013, GDHC60PIDR

GlobalData (2014). PharmaPoint: Crohn’s Disease – Global Drug Forecast and Market

Analysis to 2022, January 2014, GDHC77PIDR

GlobalData (2014). Crohn’s Disease – US Drug Forecast and Market Analysis to 2022,

January 2014, GDHC208CFR

GlobalData (2014). Crohn’s Disease – 5EU Drug Forecast and Market Analysis to 2022,


GlobalData (2014). Crohn’s Disease – Canada Drug Forecast and Market Analysis to 2022,


GlobalData (2014). Crohn’s Disease – China Drug Forecast and Market Analysis to 2022,


GlobalData (2014). Crohn’s Disease – India Drug Forecast and Market Analysis to 2022,


GlobalData (2014). Cimzia (Crohn’s Disease)– Forecast and Market Analysis to 2022, January

2014, GDHC323DFR

GlobalData (2014). Entyvio (Crohn’s Disease) – Forecast and Market Analysis to 2022,

January 2014, GDHC324DFR

GlobalData (2014). Humira (Crohn’s Disease) – Forecast and Market Analysis to 2022,


GlobalData (2014). Prochymal (Crohn’s Disease) – Forecast and Market Analysis to 2022,


GlobalData (2014). Remicade (Crohn’s Disease) – Forecast and Market Analysis to 2022,




Introduction

GlobalData (2014). Stelara (Crohn’s Disease) – Forecast and Market Analysis to 2022,


GlobalData (2014). Tysabri (Crohn’s Disease) – Forecast and Market Analysis to 2022,


GlobalData (2014). Vercirnon (Crohn’s Disease) – Forecast and Market Analysis to 2022,


GlobalData (2014). Crohn’s Disease – Current and Future Players, January 2014,

GDHC1027FPR

2.3 Upcoming Related Reports

GlobalData (2014). PharmaPoint: Ulcerative Colitis – Global Drug Forecast and Market

Analysis to 2022



Appendix

10.8 About GlobalData

GlobalData is a leading global provider of business intelligence in the Healthcare industry.

GlobalData provides its clients with up-to-date information and analysis on the latest developments

in drug research, disease analysis, and clinical research and development. Our integrated business

intelligence solutions include a range of interactive online databases, analytical tools, reports and

forecasts. Our analysis is supported by a 24/7 client support and analyst team.

GlobalData has offices in New York, San Francisco, Boston, London, India, Korea, Japan,

Singapore, and Australia.

10.9 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.

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