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

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 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

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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