Table of Contents

Commercial Insight: Solid organ transplantation - The impact of new biologics, generics and reformulations - In-depth overview and 10 year outlook for currently marketed immunosuppressants for transplantation and late-stage pipeline products with this intended indication, examining clinical and commercial factors driving product differentiation and uptake.

Product Code: dmhc2456

Publication Date: 18-Dec-2008

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Overview

Introduction

The transplant immunosuppressant market has seen considerable growth in recent years, but this is expected to slow down. Two factors combine to cause a decline in the market from 2011, the limited availability of donor organs and patent expiries of several key products. Neither the shift to once-daily formulations nor the launch of novel biologic therapies will prevent the contraction.

Scope

· Forecasts for immunosuppressants used in solid organ transplantation and significant pipeline drugs (to 2017 in report and to 2018 in excel tool)

· Market overview by geographical area, including a rest of the world snapshot and a case study on the Canadian transplant market

· Future market outlook for individual products taking into account key market events, in particular patent expiry and competitor launch dates

· An overview of key companies active in the transplant market and their strategies

Highlights

Datamonitor expects immunosuppressant sales in the seven major markets to grow to about $4.7 billion annually by 2011, after which the market is forecast to slowly decline to $4.4 billion by 2017 due to key products' patent expiries. The immunosuppressant market overall will be held back by the limited availability of organs.

Bristol-Myers Squibb's once-monthly monoclonal belatacept is expected to be the top-selling single brand in the seven major markets in 2017. However, the combined sales of Astellas's tacrolimus franchise (Prograf and once-daily Advagraf) will dominate the immunosuppressant market over the next ten years.

The toxicity associated with calcineurin inhibitors will lead to more emphasis on immunosuppressive regimens that permit reduction or avoidance of products from this class while maintaining adequate immunosuppression and graft survival. This leads to a fertile environment for novel immunomodulatory approaches.

Reasons to Purchase

· Identify key opportunities and threats that will impact the use and uptake of new and existing products

· Quantify the future size and scope of the transplant immunosuppressant market and predict the performance of key compounds

· Understand and capitalize on clinical unmet needs in the market through both lifecycle management of marketed drugs and new product development

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ABOUT DATAMONITOR HEALTHCARE	2
About the Infectious Disease and Respiratory (ID&R) pharmaceutical analysis team	2
CHAPTER 1 EXECUTIVE SUMMARY	3
Strategic scoping and focus	3
Datamonitor insight into the disease market	3
Related reports	4
CHAPTER 2 MARKET DEFINITION	6
Market definition for this report	6
Countries and regions included in this report	6
Introduction to the transplantation market	7
CHAPTER 3 MARKET OVERVIEW	11
Seven major markets	11
Current and future market overview	11
The immunosuppressant market is expected to grow from $4.1 billion in 2007 to $4.4 billion in 2017	12
Belatacept will take over top-position from Prograf	13
The US will remain the largest market, but growth in Europe will be higher	15
Opportunities and threats	19
Opportunities	19
Threats	31
US	42
Current and future market assessment	42
Opportunities and threats	48
Opportunities	48
Threats	50
Japan	55
Current and future market assessment	55
Threats	60
Cultural beliefs lead to particularly low organ donation rates	60
Zenapax is not likely to become available in Japan	60
Five major European markets	61
Current and future market assessment	61
France	67
Current and future market assessment	67
Germany	69
Current and future market assessment	69
Italy	72
Current and future market assessment	72
Spain	75
Current and future market assessment	75
UK	78
Current and future market assessment	78
Rest of the world snapshot	82
Rest of the world market assessment	82
Poor people sell their organs to 'transplant tourists'	85
Alternative market scenarios	86
Advagraf is not launched in the US	87
Certican is not launched in the US	88
CHAPTER 4 BRAND DYNAMICS	90
Overview of competitive landscape	90
Patient acquisition process	91
Patient care path	92
Points of influence in the patient care path	93
Drivers of brand choice	95
Physicians in the US rely heavily on polyclonal antibodies for induction therapy while those in the five major European markets and Japan prefer monoclonal antibodies	95
Physicians in the five major European markets and Japan prescribe cyclosporine for maintenance therapy more often than those in the US	97
US formulary tier status for leading brands	99
Prograf has most favorable reimbursement status of the maintenance immunosuppressant brands	100
CellCept has more favorable reimbursement status than Myfortic	100
Trends in marketing strategies	100
Promotional spend	101
Mass media can greatly influence public opinion on organ donation	103
Prograf (tacrolimus; Astellas)	104
Drug profile	105
Product positioning	106
SWOT analysis	108
Brand forecast to 2017	109
Launch of generic tacrolimus in the US will erode Prograf's sales over time	110
Advagraf will not completely protect Astellas's tacrolimus franchise	112
Other calcineurin inhibitors	116
Cyclosporine	116
CellCept (mycophenolate mofetil; Protein Design Labs/Roche)	117
Drug profile	118
Product positioning	119
SWOT analysis	121
Brand forecast to 2017	121
Generic mycophenolate mofetil expected to have fast uptake	122
Other antimetabolites	123
Myfortic (mycophenolate acid/sodium; Novartis)	123
Bredinin (mizoribine; Asahi Kasei Pharma)	124
Azathioprine (various)	124
Rapamune (sirolimus; Wyeth)	125
Drug profile	126
Product positioning	127
SWOT analysis	129
Brand forecast to 2017	129
Certican is expected to cut Rapamune's US revenues in half if launched successfully	130
Generic sirolimus not assumed to have major impact in next 10 years	132
Thymoglobulin (rabbit antithymocyte globulin; Genzyme)	133
Drug profile	134
Product positioning	134
SWOT analysis	136
Brand forecast to 2017	136
ATG-Fresenius limits further uptake of Thymoglobulin	137
Other induction treatments	139
Monoclonal antibodies	139
Belatacept (Bristol-Myers Squibb)	140
Drug profile	140
Development overview	141
Product positioning	145
SWOT analysis	147
Drug forecast to 2017	147
Launch date and price of belatacept	151
Number of de novo transplant patients up to 2017	152
Number of de novo patients receiving belatacept	154
LCP-Tacro (tacrolimus; LifeCycle Pharma)	154
Drug profile	155
Development overview	155
Product positioning	158
SWOT analysis	159
Drug forecast to 2017	159
Other forecast pipeline products	161
Pulminiq (inhaled cyclosporine; APT Pharmaceuticals/Novartis)	161
Other pipeline products	162
CHAPTER 5 KEY DEVELOPERS	166
Strategic overview	166
Trends in corporate strategy	166
Several companies redevelop their autoimmune disease portfolio	166
Small players attempt to enter the market with me-too products	167
Astellas	168
Corporate strategy	168
Immunosuppressant portfolio assessment	169
Novartis	171
Corporate strategy	171
Immunosuppressant portfolio assessment	171
CHAPTER 6 CASE STUDIES	173
The transplantation market in Canada	173
Current immunosuppressant market assessment	173
Prograf is overtaking cyclosporine as the preferred calcineurin inhibitor	175
Launch of Myfortic has not had major impact on adjunct market	176
Thymoglobulin has rapidly become the most popular drug for induction treatment	177
Pricing and reimbursement in Canada	178
Product pricing	179
Drug reimbursement	181
Opportunities and threats	183
Opportunities	183
Threats	185
BIBLIOGRAPHY	190
Articles	190
News and press releases	202
Websites	203
Presentations	204
APPENDIX A - MARKET ASSUMPTIONS	205
New product launches	205
Patent expiries	206
Data definitions, limitations and assumptions	206
Transplantation-specific sales split	206
Standard units	209
Japanese market data	210
Derivation of sales forecasts and pricing trends	210
Forecast methodology	210
APPENDIX B	211
Contributing experts	211
Report methodology	211
About Datamonitor	211
About Datamonitor Healthcare	212
About the Respiratory and Infectious Disease analysis team	213
Disclaimer	215
List of Tables
Table 1: Sales and growth of immunosuppressant drug classes in the seven major markets, 2007-2017	11
Table 2: Sales forecasts of key immunosuppressant brands in the seven major markets ($m), 2007-2017	17
Table 3: The different organ donation systems and 2007 deceased donation rate pmp by organ, in the US and five major European markets, 2007	21
Table 4: Off-label prescription of induction treatments in the US, 2004	28
Table 5: Off-label prescription of maintenance treatments in the US, 2004	29
Table 6: Examples of tests/markers available and in development, 2008	31
Table 7: Number of transplants by organ and country in the seven major markets, 2003-07	34
Table 8: Summary of opportunities and threats in the immunosuppressant market across the seven major markets, 2008	42
Table 9: Sales and growth of immunosuppressant drug classes in the US, 2007-2017	43
Table 10: Sales forecasts of key immunosuppressant brands in the US ($m), 2007-2017	46
Table 11: Summary of opportunities and threats in the immunosuppressant market in the US, 2008	55
Table 12: Sales and growth of immunosuppressant drug classes in Japan, 2007-2017	56
Table 13: Sales forecasts of key immunosuppressant brands in Japan ($m), 2007-2017	59
Table 14: Size of the monoclonal antibody class in transplantation in Japan, the US and the five major European markets	60
Table 15: Summary of threats in the immunosuppressant market in Japan, 2008	61
Table 16: Sales and growth of immunosuppressant drug classes in the five major European markets, 2007-2017	62
Table 17: Sales forecasts of key immunosuppressant brands in the five major European markets ($m), 2007-2017	65
Table 18: Sales forecasts of key immunosuppressant brands in France ($m), 2007-2017	68
Table 19: Sales forecasts of key immunosuppressant brands in Germany ($m), 2007-2017	70
Table 20: Sales forecasts of key immunosuppressant brands in Italy ($m), 2007-2017	73
Table 21: Sales forecasts of key immunosuppressant brands in Spain ($m), 2007-2017	76
Table 22: Sales forecasts of key immunosuppressant brands in the UK ($m), 2007-2017	80
Table 23: Comparison of the top five therapies ($m) for maintenance immunosuppression in the small and emerging markets, US and five major European countries plus Japan, 2007	85
Table 24: Leading branded immunosuppressant drug sales in the seven major markets ($m), 2007-2017	91
Table 25: Key immunosuppressants in late-stage R&D pipeline in the seven major markets, 2008	91
Table 26: Representative formulary tier status in the US for key immunosuppressants, 2008	99
Table 27: Marketing strategies employed by US product websites of selected immunosuppressants, 2008	101
Table 28: Prograf - Drug profile, 2008	105
Table 29: Impacting factors on the revenues of Prograf in the seven major markets, 2007-2017	110
Table 30: Dosing of Prograf in adult transplantation patients	114
Table 31: Calculation of the average price per standard unit (SU) for Prograf and Advagraf in the US	115
Table 32: CellCept - Drug profile, 2008	118
Table 33: Impacting factors on the revenues of CellCept in the seven major markets, 2007-2018	122
Table 34: Rapamune - Drug profile, 2008	126
Table 35: Impacting factors on the revenues of Rapamune in the seven major markets, 2007-2018	130
Table 36: Thymoglobulin - Drug profile, 2008	134
Table 37: Impacting factors on the revenues of Thymoglobulin in the seven major markets, 2007-2018	137
Table 38: Belatacept - Drug profile, 2008	140
Table 39: Summary of key late-stage ongoing clinical trials for belatacept, 2008	144
Table 40: Impacting factors on the revenues of belatacept in the seven major markets, 2010-17	148
Table 41: Belatacept US patient model, 2007-2017	149
Table 42: Belatacept 5EU patient model, 2007-2017	150
Table 43: Belatacept Japan patient model, 2007-2017	151
Table 44: Calculation of the annual price of Prograf in the US	152
Table 45: LCP-Tacro - Drug profile, 2008	155
Table 46: Summary of key late-stage ongoing clinical trials for LCP-Tacro, 2008	157
Table 47: Impacting factors on the revenues of LCP-Tacro in the seven major markets, 2007-2017	160
Table 48: Leading companies in the seven major markets immunosuppressant market, 2007-2017	166
Table 49: Astellas portfolio assessment of immunosuppressants for the transplantation market, 2008	170
Table 50: Novartis portfolio assessment of immunosuppressants for the transplantation market, 2008	172
Table 51: Sales and growth of immunosuppressant drug classes in Canada, 2003-07	173
Table 52: Price per standard unit of key immunosuppressant brands in Canada, the US and the five major European markets, 2007	181
Table 53: Number of transplants in Canada and the seven major markets, 2003-07	186
Table 54: Donation rates (pmp), waiting list and number of transplantations per country in the seven major markets and Canada, 2007	187
Table 55: Datamonitor's launch dates for immunosuppressants in the seven major markets, 2007-2017	205
Table 56: Patent expiry dates for the approved immunosuppressants in the seven major markets, 2007-2017	206
Table 57: Sales split between retail and hospital market of key immunosuppressant market in the US, France and Germany, 2007	208
Table 58: Sales split between retail and hospital market of key immunosuppressant market in Italy, Spain and the UK, 2007	209
List of Figures
Figure 1: Schematic overview of the use of immunosuppressants in transplantation	10
Figure 2: Indexed total immunosuppressant drug sales by class in the seven major markets, 2003-2017	12
Figure 3: Top five immunosuppressant brands in the seven major markets, 2007 and 2017	14
Figure 4: Sales performance of the seven major markets immunosuppressant market by country, 2003-2017	16
Figure 5: Principles of the Spanish model of organ donor recruitment	20
Figure 6: Branded and generic cyclosporine market split in the US, Japan and 5EU, 2007	24
Figure 7: Prescription of immunosuppressants in the US, 2004	27
Figure 8: Projected half-lives versus actual half-lives in deceased donor transplants: 1988-1995 (including re-transplant recipients)	39
Figure 9: Indexed total immunosuppressant drug sales by class in the US, 2003-2017	44
Figure 10: Waiting list on December 31, 2007, versus number of transplantations in 2007, by country	50
Figure 11: Overview of events related to Certican (everolimus) in the US, Europe and Japan	53
Figure 12: Overview of events related to Advagraf (tacrolimus) in the US, Europe and Japan	54
Figure 13: Indexed total immunosuppressant drug sales by class in Japan, 2003-2017	57
Figure 14: Indexed total immunosuppressant drug sales by class in the five major European markets, 2003-2017	63
Figure 15: Indexed total immunosuppressant drug sales by country in the five major European markets, 2003-2017	64
Figure 16: Indexed total immunosuppressant drug sales by class in France, 2003-2017	67
Figure 17: Indexed total immunosuppressant drug sales by class in Germany, 2003-2017	69
Figure 18: Indexed total immunosuppressant drug sales by class in Italy, 2003-2017	72
Figure 19: Indexed total immunosuppressant drug sales by class in Spain, 2003-2017	75
Figure 20: Indexed total immunosuppressant drug sales by class in the UK, 2003-2017	78
Figure 21: Seven major markets versus rest of the world sales split for the maintenance immunosuppressant market, 2003 and 2007	83
Figure 22: Indexed annual sales of the maintenance immunosuppressant market in small and emerging markets, 2003-07	84
Figure 23: Main forecast versus alternative forecast for the launch of Advagraf in the US	88
Figure 24: Main forecast versus alternative forecast for the launch of Certican in the US	89
Figure 25: Solid organ transplant patient care path	92
Figure 26: Market share ($m) of the products used for induction treatment in the US, five major European countries and Japan, 2007	95
Figure 27: Market share ($m) of the products used for maintenance treatment in the US, five major European countries and Japan, 2007	98
Figure 28: Promotional spend for key brands in the US, 2007	103
Figure 29: Retail sales split of Prograf in the seven major markets, 2007	106
Figure 30: Prograf SWOT analysis, 2008	108
Figure 31: Sales of Prograf, Advagraf and generic tacrolimus in the seven major markets, 2007-2017	109
Figure 32: Market share of Neoral/Sandimmun and generic cyclosporine in the US, 2001-07 (1999-2001 assumed)	111
Figure 33: Market share of Prograf and Advagraf in Spain, Q1 2007- Q4 2009	114
Figure 34: Calculation of price difference per standard unit (SU) in the US between Prograf and Advagraf	116
Figure 35: Sales of Neoral/Sandimmun and generic cyclosporine in the seven major markets, 2007-2017	117
Figure 36: Retail sales split of CellCept in the seven major markets, 2007	119
Figure 37: CellCept SWOT analysis, 2008	121
Figure 38: Sales of CellCept and generic mycophenolate mofetil in the seven major markets, 2007-2017	122
Figure 39: Sales of azathioprine, Myfortic and Bredinin in the seven major markets, 2007-2017	125
Figure 40: Retail sales split of Rapamune in the seven major markets, 2007	127
Figure 41: Rapamune SWOT analysis, 2008	129
Figure 42: Sales of Rapamune, Certican and generic sirolimus in the seven major markets, 2007-2017	130
Figure 43: Market share of Rapamune and Certican in Germany, Q1 2004-Q2 2008	132
Figure 44: Thymoglobulin SWOT analysis, 2008	136
Figure 45: Sales of Rapamune, Thymoglobulin, ATGAM and ATG-Fresenius in the seven major markets, 2007-2017	137
Figure 46: Market share of Neoral/Sandimmun, Gengraf and other generic cyclosporine in the US, 2001-07	138
Figure 47: Sales of Rapamune, Simulect, Zenapax and Orthoclone Okt-3 in the seven major markets, 2007-2017	139
Figure 48: Clinical trial design of belatacept's key Phase II trial	141
Figure 49: Belatacept SWOT analysis, 2008	147
Figure 50: Sales of belatacept, tacrolimus and cyclosporine in the seven major markets, 2007-2017	148
Figure 51: LCP-Tacro SWOT analysis, 2008	159
Figure 52: Sales of LCP-Tacro, Astellas's tacrolimus franchise and generic tacrolimus in the seven major markets, 2007-2017	160
Figure 53: Indexed total immunosuppressant drug sales by class in Canada, 2003-07	174
Figure 54: Indexed total sales for key immunosuppressants in Canada, 2003-07	175
Figure 55: Sales of Prograf and cyclosporine in Canada, 2003-07	176
Figure 56: Sales of CellCept, azathioprine and Myfortic in Canada, 2003-07	177
Figure 57: Sales of induction treatments in Canada, 2003-07	178
Figure 58: Average delay between first launch in the world and launch in each country for drugs launched between 1999 and 2003	184

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