Table of contents

7 EXECUTIVE SUMMARY

8 PAYER INSIGHTS

8 Payers feared the launch of the PCSK9 inhibitors, but uptake has been slower than originally
expected
9 High prices of the PCSK9 inhibitors have led to access barriers and pressure to offer discounts
13 Phase III PCSK9 inhibitor trials criticized for lack of cardiovascular outcomes data, short
follow-up period, and improper implementation of appropriate comparator
13 PCSK9 inhibitors have been widely criticized for their high prices in the absence of
cardiovascular outcomes data
14 Prescribing of the PCSK9 inhibitors has been restricted to the secondary care setting
15 Physicians are audited to monitor their prescription of the PCSK9 inhibitors
16 Definition and agreement on statin intolerance is creating discussion, with the lack of a
unified approach among payers
18 Outcomes-based risk-sharing agreements are being made in the US, and potentially in some
European markets too
18 Support services offered by PCSK9 manufacturers have further differentiated the drugs at the
regional level
19 The impact of positive cardiovascular outcomes data will likely vary between countries
23 The PCSK9 inhibitors will need to demonstrate a 3% reduction in absolute risk to gain
acceptance
23 Risk reductions will need to be driven by reductions in mortality and stroke in order to be
considered clinically relevant
26 Results from Repatha’s GLASGOW trial will not impact payers’ or physicians’ perceptions of
PCSK9 inhibitor value, as cardiovascular outcomes trial data are key
26 Significantly reduced frequency of administration is viewed as an advantage, but is unlikely to
lead to price premiums
28 There is no appetite for reimbursement of the PCSK9 inhibitors in primary prevention patients
28 Bibliography

31 US PRICING

32 US REIMBURSEMENT

32 Insights and strategic recommendations
32 Prior authorization is a key utilization management tool for the PCSK9 inhibitors
38 Formulary exclusion and tier positioning are also key utilization management tools
40 Commercial payers have entered into risk-sharing agreements for the PCSK9 inhibitors
41 Payer restrictions are likely to ease following outcomes data
42 ICER suggests lowering prices of PCSK9 inhibitors by 50–85% would result in removal of prior
authorization requirements
42 Bibliography

44 JAPAN

44 Price premiums are awarded for added benefit or innovation
45 There is no price differentiation between Praluent and Repatha in Japan
46 Bibliography

47 FIVE MAJOR EU MARKETS PRICING

48 FRANCE

48 Insights and strategic recommendations
48 ASMR rating has an impact on pricing
49 No additional benefit found for Praluent or Repatha in primary hypercholesterolemia patients
due to lack of outcomes data and clinical trial flaws
53 Transparency Committee recommends the reimbursement of Repatha in HoFH patients due to
the high unmet need that exists
53 Repatha and Praluent will require positive cardiovascular outcomes data in order to gain
reimbursement in primary hypercholesterolemia and mixed dyslipidemia patients
54 The PCSK9 inhibitors’ ASMR will depend on the magnitude of effect observed in their
cardiovascular outcomes trials and the defined patient populations
55 CEPS is likely to implement a reward scheme for the PCSK9 inhibitors, similar to that used for
novel oral anticoagulants
55 Bibliography

57 GERMANY

57 Insights and strategic recommendations
57 Positive assessment from the G-BA will impact pricing negotiations
61 PCSK9 inhibitor prescribing is currently restricted to specialist physicians who are frequently
audited
62 The PCSK9 inhibitors will likely be recommended for a larger subgroup following
cardiovascular outcomes data, and their price will come down
63 Bibliography

64 ITALY

64 Insights and strategic recommendations
64 AIFA is likely to impose only moderate restrictions on patient eligibility for the PCSK9
inhibitors
65 Prices will be negotiated down, and ceiling expenditure agreements are likely to be put in
place

67 SPAIN

67 Insights and strategic recommendations
67 National reimbursement decisions are not a barrier to access
67 IPTs judged that both PCSK9 inhibitors offer additional therapeutic benefit
68 LDL-C cutoff levels defined by IPTs are relatively low in comparison to other European
countries
70 Regional assessments are an additional market access step
70 Spanish payers place more importance on GÉNESIS regional reports than on IPTs

LIST OF TABLES

70 Regional and hospital payers have defined higher LDL-C cutoff levels than the IPTs
71 Regional and hospital payers may have a preferred brand
72 The PCSK9 inhibitors are hospital drugs, and patient eligibility is assessed on a case-by-case
basis
73 Reimbursement restrictions may ease slightly following the demonstration of improved
cardiovascular outcomes
74 Risk-sharing agreements have been proposed but not yet agreed
74 Bibliography
75 UK
75 Insights and strategic recommendations
75 NICE approval is a key market access barrier
76 LDL-C cutoff levels have been calculated using ICERs
79 The PCSK9 inhibitors require patient access schemes to have an acceptable ICER
79 An online prior authorization platform will be used to control access to the PCSK9 inhibitors
79 Regional formulary decisions
83 Positive cardiovascular outcomes results are not expected to have any impact on
reimbursement of the PCSK9 inhibitors
83 Scottish Medicines Consortium recommends Praluent but rejects Repatha
87 Bibliography

88 METHODOLOGY

88 Primary research methodology
88 Price assumptions
90 Exchange rates
90 Bibliography
11 Table 1: Levers impacting access to the PCSK9 inhibitors in the US and five major EU markets,
by country
22 Table 2: Impact of positive CV outcomes data on reimbursement of the PCSK9 inhibitors, by
country
31 Table 3: Pricing of the PCSK9 inhibitors in the US
34 Table 4: Prior authorization criteria for PCSK9 inhibitors with major health insurers and
pharmacy benefit managers
38 Table 5: Formulary placement of PCSK9 inhibitors in selected commercial formularies
39 Table 6: Formulary placement of PCSK9 inhibitors in selected Medicare formularies
44 Table 7: Japan – pricing premiums given to medicines that can demonstrate benefit over
comparators
45 Table 8: Pricing methods for the PCSK9 inhibitors
45 Table 9: Pricing of the PCSK9 inhibitors in Japan
47 Table 10: Pricing of the PCSK9 inhibitors in the five major EU markets, by country
48 Table 11: Transparency Committee’s ASMR ratings and pricing implications
49 Table 12: Transparency Committee’s SMR ratings and pricing implications
51 Table 13: Transparency Committee’s assessment of PCSK9 inhibitors
58 Table 14: G-BA’s assessment of PCSK9 inhibitors
69 Table 15: Therapeutic positioning reports for PCSK9 inhibitors in Spain
77 Table 16: NICE’s assessment of PCSK9 inhibitors
82 Table 17: UK regional formulary decisions for PCSK9 inhibitors
85 Table 18: SMC’s assessment of PCSK9 inhibitors
88 Table 19: Price sources and calculations for the US
88 Table 20: Price sources and calculations for the EU
90 Table 21: Exchange rates used for calculating branded drug prices