Commercial Insight: Solid organ transplantation - The impact of new biologics, generics and reformulations

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 214

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