TABLE OF CONTENTS

7 EXECUTIVE SUMMARY
8 MARKET CONTEXT
8 While traditional first-line medications face generic competition, pipeline triple combinations and LABA/LAMAs will fuel modest growth in COPD
8 Marketed COPD products in the US, Japan, and five major EU markets
13 Pipeline COPD treatments in late-stage development
17 Bibliography
21 GLOBAL PAYER AND KEY OPINION LEADER INSIGHTS
21 Insights and strategic recommendations
22 Physicians are looking forward to triple therapy combinations for severe COPD patients
22 Payers are less impressed with triple therapy combinations, with potential for overprescribing a concern
26 LABA/LAMAs set to overtake ICS/LABAs in non-exacerbating COPD patients
31 Key opinion leaders believe IL-5 biologics are unlikely to play a major role in COPD
32 Some payers welcome second-generation LAMAs, but they are unlikely to displace Spiriva as the market leader
34 Unclear product differentiation among branded ICS/LABA products is driving price competition
37 Reversal of disease progression is considered one of the main unmet needs in COPD
40 Once-daily dosing matters less to physicians than having access to both once-daily and twicedaily inhalers
41 US and EU payers and physicians want more economically impactful, easily quantified outcomes
42 Longer clinical trials with clinically significant results favored by both US and EU payers
44 Bibliography
45 US PRICING
45 Pricing of LABA/LAMAs is comparable to ICS/LABAs
46 Spiriva Respimat is priced at a 50% discount over the HandiHaler device
46 Bibliography
47 US PAYER INSIGHTS
47 Insights and strategic recommendations
47 Co-pays continue to determine patients’ therapeutic choices
47 Payers will welcome generic ICS/LABA inhalers, but physicians are more skeptical
49 Strong respiratory portfolio opens possibility for bundled contracting with some payers
50 Bibliography
51 US REIMBURSEMENT
51 Insights and strategic recommendations
51 Trends in COPD drug expenditure
54 GOLD guidelines are widely used for COPD
56 Formulary tier positioning is the key utilization management tool used in COPD
78 Generic Advair entry to the US market is a real threat for GlaxoSmithKline
79 Bibliography
84 JAPAN
84 Price premiums are awarded for added benefit or innovation
88 Pricing of launched COPD treatments
88 Pricing of LABA/LAMAs in Japan is considerably higher than ICS/LABAs
89 Bibliography
90 FIVE MAJOR EU MARKETS PRICING
93 First-to-market Utibron enjoys high prices in most EU markets
94 FIVE MAJOR EU MARKETS PAYER INSIGHTS
94 Insights and strategic recommendations
94 Inhaler spend is one of the top budget items for European payers with high visibility
95 Access to COPD inhalers relatively unrestricted in the five major EU markets
101 With the exception of the UK, GOLD remains the most frequently used guideline in EU countries
101 Bibliography
102 GENERIC ICS/LABA INHALERS IN THE FIVE MAJOR EU MARKETS
102 Insights and strategic recommendations
102 Generic versions of Advair and Symbicort struggle to gain market share
113 Generic versions of Advair have received limited approval and continue to see low market penetration in the EU
114 Generic Symbicort product DuoResp gains traction in the EU
114 Generic tiotropium uptake highly dependent on determination of device substitutability for single inhaler LAMAs
115 Bibliography
118 FRANCE
118 Insights and strategic recommendations
118 ASMR rating has an impact on pricing
127 Head-to-head trials of LABA/LAMAs vs ICS/LABAs likely to trigger a review by the TC and permit further education efforts
128 ICS/LABA/LAMA combinations unlikely to receive ASMR higher than V
128 Branded generic versions of Advair and Symbicort have been reviewed by the TC
128 Bibliography
131 GERMANY
131 Insights and strategic recommendations
131 Positive assessment from the G-BA will impact price negotiations
142 Sickness funds tender for branded combination ICS/LABAs; uptake of generics remain low
143 COPD medications are subject to indicative budget limits but relevance of this restriction may change under ongoing reforms
145 Bibliography
147 ITALY
147 Insights and strategic recommendations
147 AIFA is responsible for pricing and reimbursement decisions
153 Delays in inclusion on regional formularies hamper access for recently launched inhalers
154 Approvals of LABA/LAMAs Anoro and Utibron with treatment plan provision will further restrict market uptake
155 AIFA register is an access obstacle for Daliresp; prescription volumes remain low
155 In the absence of restrictions from AIFA and regional decision-makers, the choice between branded vs generic combination inhaler is left to the physician
156 Bibliography
159 SPAIN
159 Insights and strategic recommendations
159 National reimbursement decisions are not a barrier to access
159 Some general physicians are subjected to prescribing limitations for COPD drugs
164 None of the COPD drugs evaluated in IPTs offer additional therapeutic benefit
164 Regional assessments are an additional market access step
169 Bibliography
173 UK
173 Insights and strategic recommendations
173 NICE approval is a key access barrier in the UK
176 Daliresp is restricted to patients with COPD currently undergoing clinical trials
176 NICE recommends most economical option for LABA/LAMA combinations; choice down to regional commissioners
183 NICE COPD treatment guidelines are used by NHS physicians
184 SMC decisions
193 Bibliography
197 METHODOLOGY
197 Price assumptions
201 Exchange rates
201 Bibliography
183 Figure 1: NICE COPD guideline, 2010

LIST OF TABLES

9 Table 1: Marketed products and approved indications for COPD in the US, Japan, and five major EU markets
14 Table 2: Late-stage candidates in development for COPD
45 Table 3: US pricing of key marketed drugs
52 Table 4: Asthma and COPD spend by payers, 2014
52 Table 5: Top 10 asthma and COPD drug spend by Express Scripts members
54 Table 6: Spend on the top three asthma and COPD drugs by Medicare Part D beneficiaries, 2013
54 Table 7: COPD GOLD patient categorization and recommended treatments, 2015
55 Table 8: GOLD airflow limitation risk groups
57 Table 9: Formulary placement of COPD drugs in selected commercial formularies
63 Table 10: Formulary placement of COPD drugs in the top five 2015 Medicare Part D formularies
70 Table 11: Formulary placement of COPD drugs in selected large Medicaid states’ preferred drug lists
71 Table 12: Express Scripts’ TRICARE formulary placement of COPD drugs
74 Table 13: CVS Caremark’s and Express Scripts’ formulary-excluded COPD drugs
75 Table 14: Prior authorization criteria for COPD drugs by major health insurers and pharmacy benefit managers
84 Table 15: Japan – pricing premiums given to medicines that can demonstrate benefit over comparators
86 Table 16: Price calculation methodologies for COPD drugs in Japan launched after 2008
88 Table 17: Pricing of key marketed COPD drugs in Japan
91 Table 18: Annual treatment cost of COPD drugs in the five major EU markets
98 Table 19: Access controls for COPD medications in the five major EU markets
103 Table 20: Availability and substitutability of branded generic inhalers in the five major EU markets
107 Table 21: List price differential between branded ICS/LABAs and branded generics for COPD in the five major EU markets
111 Table 22: Market access levers impacting ICS/LABA generic inhaler uptake in the five major EU markets
118 Table 23: Transparency Committee’s ASMR ratings and pricing implications
119 Table 24: Transparency Committee’s SMR ratings and pricing implications
120 Table 25: Transparency Committee’s assessment of COPD treatments
133 Table 26: G-BA assessment of key COPD therapies
148 Table 27: Reimbursement conditions for COPD treatments in Italy
151 Table 28: Italy local formulary decisions for COPD drugs
161 Table 29: Therapeutic positioning reports for COPD drugs in Spain
166 Table 30: Spain regional assessments of COPD drugs
175 Table 31: NICE assessments of key COPD therapies
178 Table 32: CCG formulary inclusions for key COPD drugs
185 Table 33: SMC decisions on key COPD therapies
197 Table 34: Price sources and calculations for the US
199 Table 35: Price sources and calculations for the EU
201 Table 36: Exchange rates used for calculating branded drug prices