CONTENTS

8 OVERVIEW

9 EXECUTIVE SUMMARY

10 REGULATORY LABELS
10 Marketed ovarian cancer products in the US, Japan, and five major EU markets
16 Bibliography

17 GLOBAL ACCESS LEVERS
17 Budget for ovarian cancer medicines less of a concern for payers
18 Access to ovarian cancer medicines is relatively unrestricted
23 Combination treatments may present a particular challenge in the future

25 EVIDENCE AND VALUE
25 Overall survival remains the gold standard endpoint for ovarian cancer
27 PFS is an acceptable endpoint for certain patient populations
30 Real-world evidence can be used to supplement PFS data
31 OS remains the gold standard endpoint for immunotherapies

33 ACCESS TO RECENTLY APPROVED AND PIPELINE PRODUCTS
34 Lynparza is reimbursed in major markets with little restriction
36 Access conditions for Zejula and Lynparza in wtBRCA population likely to vary by market
40 Payers unlikely to compare safety and efficacy of PARP inhibitors for HTA decision making
47 Contracting for PARP inhibitors unlikely for the foreseeable future
49 Immuno-oncology drugs are managed as part of the wider oncology indication
50 PD-L1 stratification is likely to be advantageous despite lack of payer consensus on advantages of biomarker selection
53 Tecentriq/Avastin combination may have an advantage over Bavencio in markets where Avastin is already standard of care
57 Developers of pipeline immunotherapies need to ensure checkpoint inhibitor schedule is aligned with chemotherapy

59 PRICING

60 US
60 Insights and strategic recommendations
60 Commercial formularies are similar in terms of formulary positioning for ovarian cancer drugs
62 Medicare formularies largely include ovarian cancer drugs
64 Prior authorization is the key utilization management tool used in ovarian cancer
68 AIM Specialty Health outlines ovarian cancer pathway
70 NCCN follows FDA label for most of the approved ovarian cancer medicines
71 Lynparza in BRCAm+ patients is the only cost-effective PARP inhibitor according to ICER
72 Payers question ICER’s influence on pricing
73 Payers are unlikely to contract for PARP inhibitors in the near term
74 Lax utilization management of checkpoint inhibitors negates necessity to have biomarker testing
75 Contracting for PD-1 inhibitors unlikely to happen until multiple drugs have broad overlapping indications
75 Bibliography

78 JAPAN
78 Bibliography

80 FRANCE
80 Insights and strategic recommendations
80 ASMR rating has an impact on pricing
90 Avastin received minor added benefit for use in first-line patients only, no added benefit in other settings
90 Lynparza received minor added benefit from the TC
91 Lynparza likely to have minor added benefit in both BRCAm+ and wtBRCA patient population
92 Oral medicines face fewer access barriers in France
92 Tecentriq and Bavencio likely to have smooth path to reimbursement, but price-volume agreements and budget ceilings will limit commercial potential overall
93 Payers and KOLs express preference towards combination therapy with Avastin/Tecentriq and chemotherapy over Bavencio and chemotherapy
93 Bibliography

95 GERMANY
95 Insights and strategic recommendations
96 Positive assessment from the G-BA will impact price negotiations
96 Orphan drugs have an added benefit by law regardless of the available evidence
97 G-BA does not have specific thresholds for overall survival; relative improvement is most important
101 Zejula will be given an added benefit in the first G-BA assessment, but the price is likely to be below Lynparza’s
102 Bavencio and Tecentriq will undergo full benefit assessment; OS data will be crucial to demonstrate added value
103 Biomarker testing poses an access issue in Germany
104 Bibliography

105 ITALY
105 Insights and strategic recommendations
105 Avastin and Lynparza are subject to AIFA web monitoring
108 Ovarian cancer drugs assessed and reimbursed by AIFA are found in Emilia-Romagna regional formulary
108 Emilia-Romagna does not recommend Avastin with carboplatin and gemcitabine in first recurrence
108 Emilia-Romagna recommends use of Avastin in first-line advanced ovarian cancer patients
109 Lynparza recommended for use in subset of BRCAm+ platinum-sensitive patients
110 PARP inhibitors unlikely to be innovative according to AIFA regulations
110 PD-1 immuno-based therapies likely to be reimbursed by AIFA but could face local access hurdles
110 Pricing for immunotherapies unlikely to change with additional indications
111 Tecentriq’s combination therapy with Avastin may be at an advantage over Bavencio
111 Bibliography

113 SPAIN
113 Insights and strategic recommendations
113 National reimbursement decisions are not a barrier to access
114 Regional access to ovarian cancer treatments varies in Spain
119 Andalucía’s therapeutic committee excludes Avastin from formulary
120 Catalonia’s regional therapeutics committee restricts use of Avastin and Lynparza
120 PARP inhibitors are unlikely to be used outside of the BRCA mutated population
120 Payers foresee having preference for one PARP inhibitor when three are in the market
121 Payers recommend immunotherapy treatments tailored to specific subgroups
121 Bibliography

123 UK
123 Insights and strategic recommendations
124 NICE approval is a key market access barrier
137 Avastin’s unlicensed dose is reimbursed via the CDF in first-line patients with ovarian cancer
137 Access to Lynparza restricted to use after failure with three chemotherapy regimens, with a PAS
138 NICE rejects Zejula in ovarian cancer, but recommends application to the CDF
138 Zejula’s pricing at launch is key to market penetration
139 Price competition for PARP inhibitors could occur in the future when multiple drugs launch
140 AstraZeneca has a narrow window of opportunity to utilize its first-to-market advantage by lowering Lynparza’s price
140 New Cancer Drugs Fund addresses inefficiency issues with former fund mechanism
141 Tecentriq/Avastin and chemotherapy combination may face higher access hurdles compared to Bavencio and chemotherapy
142 UK payers want biomarker stratification for PD-L1 inhibitors
143 Cost effectiveness in lowest-value indication drives the price for checkpoint inhibitors
156 Bibliography

158 METHODOLOGY
158 Primary research
158 Price assumptions
161 Exchange rates
161 Bibliography

LIST OF TABLES
11 Table 1: Marketed products and approved indications for ovarian cancer in the US, Japan, and five major EU markets
21 Table 2: Levers impacting access to ovarian cancer drugs in the US and five major EU markets
35 Table 3: Market access controls for Lynparza
37 Table 4: Market access scenario for Zejula and Lynparza in the wtBRCA population
42 Table 5: Efficacy and safety comparison of PARP inhibitors in selected studies
59 Table 6: Pricing of key ovarian cancer drugs in the US, Japan, and five major EU markets, by country, 2017
61 Table 7: Formulary placement of ovarian cancer medications in selected commercial formularies
63 Table 8: Formulary placement of ovarian cancer medications in selected Medicare formularies
66 Table 9: Prior authorization criteria for ovarian cancer drugs in major health insurers and PBMs
69 Table 10: AIM Specialty Health Oncology Pathway
71 Table 11: NCCN guidelines for ovarian cancer medicines
72 Table 12: PARP inhibitor drug pricing compared to ICER value-price benchmarks
78 Table 13: Japan – pricing premiums given to medicines that can demonstrate benefit over comparators
81 Table 14: Transparency Committee’s ASMR ratings and pricing implications
81 Table 15: Transparency Committee’s SMR ratings and pricing implications
82 Table 16: Transparency Committee’s assessment of ovarian cancer treatments
99 Table 17: G-BA assessment of key ovarian cancer therapies
106 Table 18: Reimbursement conditions for ovarian cancer treatments in Italy
108 Table 19: Italian regional formulary decisions for ovarian cancer drugs
114 Table 20: Therapeutic positioning reports for ovarian cancer drugs in Spain
115 Table 21: Spanish Society of Hospital Pharmacy ratings
116 Table 22: Regional MADRE assessments for ovarian cancer drugs
125 Table 23: NICE assessments of key ovarian cancer therapies
144 Table 24: SMC decisions on key ovarian cancer therapies
159 Table 25: Price sources and calculations for the US
160 Table 26: Price sources and calculations for the EU
161 Table 27: Exchange rates used for calculating branded drug prices