TABLE OF CONTENTS

6 EXECUTIVE SUMMARY
6 Regulatory pathway
6 Substitution and naming
7 Legal considerations
7 Pricing, reimbursement, and access
8 Education needs

9 THE NEED FOR BIOSIMILARS
9 What are biosimilars?
9 The US has lagged behind the EU in developing a regulatory process for biosimilars
10 Biosimilars are expected to deliver considerable cost savings for the US healthcare system
11 There are several questions around biosimilars that need to be addressed
12 Bibliography

14 REGULATORY PATHWAY
17 Omnitrope was a “copy” biologic that was approved prior to 2010 via the 505(b)(2) process
18 Basaglar was the second “copy” biologic approved in the US through the 505(b)(2) pathway
18 The BPCI Act established a dedicated biosimilar approval pathway in the US
20 The FDA has released guidance on biosimilar approval requirements
24 There are still several uncertainties around the regulatory pathway in the US
28 Indication extrapolation poses the greatest regulatory uncertainty for manufacturers
32 There are several key differences in US and EU approval processes
34 Zarxio was the first biosimilar to be approved through the BPCI Act pathway
36 Three more US biosimilars have since been approved: Inflectra, Erelzi, and Amjevita
36 Bibliography

43 SUBSTITUTION AND NAMING POLICY
43 Biosimilars naming is a contentious issue
44 Biosimilar labeling was a key issue with Zarxio, but seems to have been resolved with the newest approvals
45 Substitution policies are likely to vary across states
53 Bibliography

55 LEGAL ISSUES
55 The innovative industry lobby secured a long period of exclusivity for biologics
55 Biologics currently have four years of data exclusivity followed by eight years of market exclusivity
58 Patent litigation is being pursued by many originator companies
69 Bibliography

73 PRICING, REIMBURSEMENT, AND ACCESS
73 Different tools are used to control spending on biologics
74 Biosimilars are expected to offer at least 20% discounts relative to the brand
79 Biosimilar use will be driven by a number of measures
90 Payers’ drive to promote biosimilar use depends on the indication
92 Payers will treat biosimilars as brands
93 Accountable care organizations and group purchasing organizations will have an interest in using biosimilars
94 Bibliography

98 EDUCATION AND COMMUNICATION NEEDS
98 There are still residual uncertainties regarding biosimilars in the eyes of many stakeholders
98 A large proportion of physicians have had concerns about biosimilars, but perceptions are changing
101 Patients likely to accept biosimilars
102 Education around biosimilars is critical for access and uptake in the US
105 Concerted education efforts are required in order to boost biosimilar acceptance and use
107 Bibliography

LIST OF FIGURES
9 Figure 1: Definitions of various types of biologics and copy products
10 Figure 2: Key events in the evolution of regulatory environments for biosimilars
17 Figure 3: Approval pathways available for biologics in the US
60 Figure 4: Information exchange steps between biosimilars manufacturers and reference product patent holders
87 Figure 5: Biosimilars reimbursement under Medicare Part B
103 Figure 6: US healthcare professionals’ understanding of biosimilars
106 Figure 7: Key organizations involved in stakeholder education about biosimilars

LIST OF TABLES
15 Table 1: Key US biosimilar regulatory events
19 Table 2: Committees created to support biosimilar approval
21 Table 3: FDA guidance on biosimilars published to date
23 Table 4: Key scientific principles used for biosimilar application review
27 Table 5: FDA interchangeability requirements for biosimilars
29 Table 6: Regulatory considerations for indication extrapolation for biosimilars
32 Table 7: Factors influencing physician acceptability and likelihood of indication extrapolation
33 Table 8: Differences in US and EU biosimilar definitions, regulatory guidance, and other key regulatory factors influencing biosimilar approval and use
46 Table 9: Biosimilar substitution: select state laws and legislation
55 Table 10: Key features of the BPCI Act
58 Table 11: Data, market exclusivity, and patent expiry dates in the US for selected biologics
62 Table 12: Summary of ongoing legal challenges
74 Table 13: Utilization tools for the management of biologics spending
80 Table 14: Utilization tools applied to biosimilars
91 Table 15: Payer strategies aimed at increasing biosimilar uptake will vary by indication and product characteristics
92 Table 16: Prior authorization criteria from major health insurers for Neupogen