Table of Contents

8 OVERVIEW

9 EXECUTIVE SUMMARY

10 REGULATORY LABELS
10 AML products in the US, Japan, and five major EU markets
13 Bibliography

14 GLOBAL ACCESS LEVERS
14 Insights and strategic recommendations
14 The budget impact of AML is currently small, but is likely to increase following further approvals
16 Payers currently have a relatively passive approach to AML
17 Moderate levels of restriction are imposed on marketed AML medicines Vidaza and Dacogen
22 AML treatment is becoming increasingly personalized
26 Combinations are likely to be the future of AML
26 Efficacy trumps route of administration in AML due to high unmet need
28 Recently approved and pipeline AML therapies are likely to seek multiple label expansions, resulting in subsequent price decreases
37 Bibliography

39 EVIDENCE AND VALUE
39 Insights and strategic recommendations
39 OS is considered the most important endpoint, but PFS is sometimes sufficient
41 Threshold for OS improvement varies with line of therapy
42 HRQoL data are important, yet rarely collected
42 Age may not be the best predictor of treatment eligibility
43 “Investigator choice” is accepted but needs to reflect SoC in each market
44 Improvements in complete remission rate are important as they indicate an increased eligibility for stem cell transplants
45 Bibliography

46 ACCESS TO RECENTLY APPROVED AND PIPELINE PRODUCTS
46 Rydapt
46 Gilteritinib and quizartinib
46 Vyxeos
46 Guadecitabine and Venclexta
47 Rydapt has the potential to gain positive pricing and reimbursement recommendations, but EU payers might restrict by age
50 Second-generation FLT3 inhibitors could improve clinical outcomes; if not, price will be an important factor
52 Vyxeos likely to be impacted by different funding mechanisms
54 Vyxeos likely to benefit from more favorable infusion schedule
55 Generic Vidaza will set the price benchmark in Europe for certain pipeline therapies
56 Bibliography

57 PRICING

59 US
59 Insights and strategic recommendations
59 There are minimal controls for AML therapies
61 Uptake will largely be dictated by specialist physicians
62 New oral AML therapies found in tier 3 of most commercial formularies
70 Prior authorization generally follows FDA labels for recently approved AML therapies
72 Bibliography

74 JAPAN
74 Price premiums are awarded for added benefit or innovation
75 Bibliography

76 FRANCE
76 Insights and strategic recommendations
76 ASMR rating has an impact on pricing
82 Dacogen is not included on the “liste-en-sus” and is unlikely to be routinely reimbursed in the hospital setting
82 Vidaza reimbursed only for those with 20–30% blasts
83 Exclusion from the liste-en-sus will likely be a cost-containment measure for new hospital-administered drugs
84 Oral AML therapies will be fully reimbursed irrespective of ASMR rating
85 Relapsed and refractory AML patients are considered to have the highest unmet need
85 Mutationally targeted therapies may be able to achieve higher prices in negotiations with the CEPS
86 Vyxeos could gain an ASMR III in France, and be used alongside chemotherapy add-ons that are expected to gain approval
86 Bibliography

88 GERMANY
88 Insights and strategic recommendations
88 Positive assessment from the G-BA will impact price negotiations
91 Recently approved and pipeline orphan therapies will be given an automatic additional benefit rating from the G-BA
91 Without mature Phase III data, orphan drugs are likely to receive “no additional benefit” at the second G-BA assessment
93 Dacogen received a minor additional benefit rating due to unclear OS data
93 Price negotiations after the benefit assessment are the main levers for sickness funds to control expenditure on AML drugs
94 Cost-containment tools for AML may be implemented as the market gets more crowded
94 Label expansions to wider patient populations will result in multiple G-BA assessments and pricing negotiations
95 Unmet need is not considered in an added benefit assessment by the G-BA
95 Mutationally targeted therapies will not be viewed more favorably by the G-BA, and reimbursement of genetic tests may be an issue
96 Expensive AML medications will require an NUB to gain funding through the hospital system
97 Vyxeos is unlikely to be assessed by the G-BA, and access will depend heavily on price
97 Safety issues are likely to limit IDHIFA’s uptake in the German market
98 Bibliography

99 ITALY
99 Insights and strategic recommendations
99 All marketed AML treatments are reimbursed in Italy
101 AML drugs assessed and reimbursed by AIFA are found in regional formularies investigated by Datamonitor Healthcare
102 Some Italian regions impose further restrictions
104 Gaining a therapeutic innovation rating will be highly beneficial for new AML medications
107 Rydapt has the potential to receive “innovative” or “conditionally innovative” drug status
108 Bibliography

109 SPAIN
109 Insights and strategic recommendations
109 National reimbursement decision is not a major access barrier in Spain
109 Regional and local bodies give more stringent reimbursement recommendations
110 Restrictions from local authorities often have the greatest impact
112 Dacogen received a broad recommendation in its IPT
112 Recommendations for Dacogen and Vidaza differ regionally and locally
113 Drugs targeting the relapsed/refractory setting may gain easier access
113 Label expansions will result in price decreases in Spain
113 Mutationally targeted therapies are likely to be assessed more favorably in Spain
114 Early access can be granted in Spain for one year, based on provisional data
115 Vyxeos is expected to be recommended at a national level, but pricing and local recommendations will be the most important

115 Bibliography

117 UK
117 Insights and strategic recommendations
117 NICE and SMC determinations drive reimbursement decisions
125 NICE and SMC recommend Vidaza for patients with 20–30% blasts only
125 Vidaza required PAS for acceptance by NICE and SMC
125 Dacogen is not available on the UK or Scottish healthcare system
125 NICE committee fails to recommend Rydapt for reimbursement
126 Cancer Drugs Fund redesigned for goal of early access to novel drugs
126 Payers are likely to be more “reactive” rather than “proactive”
127 Treatment algorithms will likely have an important impact on the uptake of AML therapies in the future
128 Bibliography

130 APPENDIX
130 Primary research
130 Price assumptions
131 Exchange rates
132 Bibliography

LIST OF FIGURES
131 Figure 1: Price sources and calculations, by country

LIST OF TABLES
11 Table 1: Marketed products and approved indications for acute myeloid leukemia in the US, Japan, and five major EU markets
19 Table 2: Factors influencing the pricing and reimbursement of Vidaza and Dacogen in the US and five major EU markets
25 Table 3: Pricing and reimbursement of mutationally targeted therapies in the US and five major EU markets
30 Table 4: Investigated populations for recently approved and pipeline AML therapies
53 Table 5: The impact of in-patient funding mechanisms on Vyxeos’s use
58 Table 6: Pricing of key AML drugs in the US, Japan, and five major EU markets, by country
63 Table 7: Formulary placement of marketed AML drugs in selected commercial formularies
67 Table 8: Formulary placement of marketed AML drugs in select Medicare Part D formularies
71 Table 9: Prior authorization criteria for marketed AML drugs in six major health plans
74 Table 10: Pricing premiums given to medicines that can demonstrate benefit over comparators
77 Table 11: Transparency Committee’s ASMR ratings and pricing implications
78 Table 12: Transparency Committee’s SMR ratings and pricing implications
79 Table 13: Transparency Commission’s assessment of AML treatments
90 Table 14: G-BA assessments of key AML drugs
100 Table 15: Reimbursement conditions for AML treatments in Italy
102 Table 16: Italian regional formulary decisions for AML drugs
103 Table 17: AML drug assessments by the Emilia-Romagna region
105 Table 18: AIFA Technical Scientific Committee innovation algorithm
111 Table 19: National and regional reimbursement decisions in Spain
118 Table 20: NICE assessments of key AML therapies
123 Table 21: SMC decisions on key AML therapies
132 Table 22: Exchange rates used for calculating branded drug prices