Table of Contents

7 EXECUTIVE SUMMARY

8 REGULATORY LABELS
16 Only a handful of hemophilia agents have an orphan drug designation
16 Bibliography
18 GLOBAL PAYER AND KEY OPINION LEADER INSIGHTS
18 Insights and strategic recommendations
18 Payer archetypes and trends in access
23 Payers and key opinion leaders’ views on hemophilia management and expenditure
41 Evidentiary requirements for demonstrating added benefit
48 Hemophilia pipeline
56 Gene therapies will need to overcome multiple barriers to achieve access
59 Bibliography

61 US PRICING
65 Increases in annual costs in-line with extent of technology improvement
66 While pricing trends in the US were looking towards greater cost-control at one point, the future is no longer clear
67 Bibliography

69 US REIMBURSEMENT
69 Insights and strategic recommendations
69 Trends in hemophilia drug expenditure
70 Cost-containment strategies
71 Payers have limited utilization management options despite rising costs
80 With broad FDA labels, treatment guidelines help to refine treatment decisions
82 Prior authorization criteria are largely in line with FDA label and treatment guidelines
91 Bibliography

94 FIVE MAJOR EU MARKETS PRICING
99 Spain and Germany sit at opposite ends of the hemophilia annual drug costs range
100 Bibliography

101 FRANCE
101 Insights and strategic recommendations
101 Access to drugs in France is relatively unrestricted beyond European marketing authorization
101 ASMR rating has an impact on pricing
111 In line with the available evidence, the general use of some hemophilia drugs and mode of therapy is restricted to select patient groups
111 For longer-acting agents, an active comparator trial is key to achieving ASMR IV
113 The bulk of hemophilia agents are on the retrocession list, which might undergo tighter controls in the future
114 Performance-based risk-sharing agreements are likely to be implemented for novel agents
115 While not necessarily limiting access, hospital-based tenders further help contain drug costs
115 Bibliography

117 GERMANY
117 Insights and strategic recommendations
117 Positive assessment from the G-BA will impact price negotiations
121 Physician office delivery of clotting factors hinders payers’ ability to influence product selection
122 Due to high budget impact, sickness funds may contract for factor VIII products
122 Emicizumab’s potential inclusion in the public pharmacy delivery could allow for better utilization tools
123 Bibliography

124 ITALY
124 Insights and strategic recommendations
124 All reviewed hemophilia treatments are reimbursed in Italy
127 Delays in AIFA decisions for newly launched biologics hamper access
129 Regional and hospital tendering further reduce drug costs without impacting on market accessibility
130 Bibliography

132 SPAIN
132 Insights and strategic recommendations
132 No assessments have been made for hemophilia drugs in Spain
133 Access is highly restricted due to the limited number of specialized centers
133 Best price dictates market share through regional and hospital-based tendering mechanisms
135 Bibliography

136 UK
136 Insights and strategic recommendations
136 NHS England adopts a national procurement system to contain costs
142 Clinical reference group within NHS England sets out guidelines for access
143 Products with novel mechanisms of action are likely to be assessed by NICE based on health economic data
144 Bibliography

146 METHODOLOGY
146 Primary research methodology
146 Price assumptions
147 Exchange rates
148 Bibliography

LIST OF FIGURES
40 Figure 1: Trough levels for standard and extended half-life factor VIII products
81 Figure 2: Treatment algorithm for hemophilia based on MASAC treatment guidelines, 2016
82 Figure 3: Treatment algorithm for hemophilia based on WFH treatment guidelines, 2012
LIST OF TABLES
9 Table 1: Approved labels for marketed hemophilia drugs in the US and five major EU markets
20 Table 2: Levers impacting access to hemophilia drugs in the US and five major EU markets
23 Table 3: Organizations involved in the procurement process in the EU
25 Table 4: Payers and key opinion leaders’ views on hemophilia management and expenditure across the US and five major EU markets
42 Table 5: Payers’ and key opinion leaders’ thoughts on evidentiary requirements for demonstrating an added benefit of new drugs
49 Table 6: Pipeline product features desired by payers and key opinion leaders
62 Table 7: Average annual costs for a severe hemophilia A patient (≥12 years of age)
64 Table 8: Average annual costs for a severe hemophilia B patient (≥12 years of age)
65 Table 9: Average annual costs for a severe hemophilia patient with inhibitors (≥12 years of age)
65 Table 10: Classifications of generations of recombinant factor VIII products according to manufacturing practice
70 Table 11: Hemophilia spend by payers, 2016 Express Scripts data
73 Table 12: Formulary placement of hemophilia recombinant products in selected commercial formularies
79 Table 13: Selected patient assistance programs by marketed drug manufacturers (manufacturer co-pay programs)
83 Table 14: Prior authorization criteria for hemophilia drugs in four major health plans
95 Table 15: Average annual episodic treatment costs for a severe hemophilia A patient
96 Table 16: Average annual prophylactic treatment costs for a severe hemophilia A patient
97 Table 17: Average annual episodic treatment costs for a severe hemophilia B patient
98 Table 18: Average annual prophylactic treatment costs for a severe hemophilia B patient
99 Table 19: Average annual episodic treatment costs for a severe hemophilia patient with inhibitors
99 Table 20: Average annual prophylactic treatment costs for a severe hemophilia patient with inhibitors
102 Table 21: Transparency Committee’s ASMR ratings and pricing implications
103 Table 22: Transparency Committee’s assessment of hemophilia treatments
118 Table 23: G-BA assessment of key hemophilia therapies
125 Table 24: Reimbursement conditions for hemophilia treatments in Italy
128 Table 25: EMA approval dates for hemophilia agents that are yet to be launched in Italy
129 Table 26: Italian regional formulary decisions
139 Table 27: NHS framework agreements for factor VIII products
140 Table 28: NHS framework agreement for factor IX products
141 Table 29: NHS framework agreement for factor VII and plasma-derived factor products
146 Table 30: Price sources and calculations for the US
147 Table 31: Price sources and calculations for the EU
148 Table 32: Exchange rates used for calculating branded drug prices