REFERENCE CODE GDHC68PIDR PUBLICATION DATE JANUARY 2014 PROPHYLACTIC HEPATITIS B VIRUS VACCINES - GLOBAL DRUG FORECAST AND MARKET ANALYSIS TO 2022
Executive Summary Prophylactic HBV Vaccines: Key Metrics in Eight Major Pharmaceutical Markets (8MM) 2012 Pediatric Vaccination Coverage Targeted Population Vaccinated Population 9.1 million 6.3 million Coverage Rate (%) 69.5 2012 Market Sales US 5EU Japan Canada 8MM Total Pipeline Assessment $528.2m $413.7m $0.2m $17.8m $959.9m Number of vaccines in Phase II III 1 Number of first-in-class vaccines 0 Most Promising Pipeline Drugs Heplisav (Dynavax Technologies) Key events (2012 2022) Launch and endorsement of Hexyon in the 5EU in 2013 2014 Launch and endorsement of V419 in the US in 2015 2016 Launch and endorsement of V419 in Canada in 2016 2017 Launch and endorsement of Heplisav in the US in 2017 2018 Launch and endorsement of Heplisav in the 5U and Canada in 2018 2019 2022 Market Sales US 5EU Japan Canada 8MM Total Source: GlobalData. Peak-Year Sales $85.6m Level of Impact $735.7m $436.4m $0.2m $19.6m $1,191.9m 5EU = five major European markets (France, Germany, Italy, Spain, UK); 8MM = eight major pharmaceutical markets included in this report (US, 5EU, Japan, Canada) Prophylactic HBV Vaccine Sales Expected to Grow During the Forecast Period GlobalData estimates that, in 2012, the global HBV vaccine market generated over $950m in sales, with the vast majority of vaccine uptake occurring in infants and young children targeted by routine immunization programs in the US, France, Germany, Italy, Spain, and Canada. GlobalData projects the market to experience modest growth through the forecast period, achieving sales of over $1.1 billion by 2022, with a compound annual growth rate (CAGR) of 2.2% from 2012 2022. Market growth is expected to be strongest in the US (3.4% CAGR), while growth in the 5EU (0.5% CAGR), Japan (2.8% negative CAGR), and Canada (1.0% CAGR) will be less pronounced. GlobalData expects that some of the most important drivers of global market growth over the next decade will be: The increased preference for pediatric combination vaccines More competition in the pediatric vaccine market The launch of Dynavax Technologies Heplisav for adults An increased emphasis on preventative medicine 2
Executive Summary GlobalData believes that notable barriers to growth of the global HBV vaccine market will include: The failed implementation of existing adult immunization recommendations Flawed adult vaccine reimbursement environments Insufficient vaccine knowledge among physicians and patients The shrinking population of adults eligible for vaccination Persistence of vaccine safety concerns Sales for HBV Vaccines by Country, 2012 2022 13.0% 15.4% 13.9% 10.3% 6.6% 0.0% 7.3% 0.3% 1.9% 7.2% Source: GlobalData. 0.2% 0.0% 1.6% 5.6% 55.0% 61.7% 2012 Total: $0.96bn United States France Germany Italy Spain United Kingdom Japan Canada 2022 Total: $1.19bn United States France Germany Italy Spain United Kingdom Japan Canada Vaccine Manufacturers Seek to Increase Vaccine Uptake by Developing Pediatric Combination Vaccines and Adult Adjuvanted Vaccines Over the last two decades, the HBV vaccine market has largely been dominated by Big Pharma, with GSK, Merck, and Sanofi as the key players. While GSK and Merck were the first companies to introduce recombinant HBsAgcontaining vaccines in the 1980s, GSK has entrenched itself as the clear market leader, accounting for over 75% of total market sales in 2012. Overall, GlobalData expects these major players to maintain their control over the marketplace despite the entrance of a new player, Dynavax Technologies, during the forecast period. Due to the HBV vaccine market s highly competitive nature, both current and future players are employing a variety of strategies to gain patient share in existing and emerging population segments. These corporate strategies include developing more immunogenic vaccines that are targeted at the adult population (Dynavax), the use of combination vaccines to protect infants against HBV (GSK, Merck, and Sanofi), and the development of more convenient HBV vaccine formulations (Merck and Sanofi). In addition to these approaches, GlobalData believes that increasing HBV vaccine uptake and decreasing cost-effectiveness concerns will be issues that all companies must recognize and include in their corporate strategies. 3
Executive Summary Company Portfolio Gap Analysis in HBV Vaccines, 2012 2022 Strength of Marketed Products High Low Source: GlobalData. Stagnant Players Low Strength of Pipeline Current and Future Players Future Players High Healthcare Providers Clamor for More Immunogenic Adult Vaccines GlobalData classifies the overall level of unmet need in the prophylactic HBV vaccine market as medium, with key opinion leaders (KOLs) from the seven major markets (7MM) and Canada identifying two key unmet needs: vaccines with improved immunogenicity, and increased vaccine uptake, with a specific focus on increasing vaccination coverage rates in at-risk adults. The poor performance of recombinant HBsAg vaccines in non-responders has been welldocumented, and vaccine manufacturers are attempting to address these shortcomings. GSK markets an adjuvanted HBV vaccine in the 5EU, Fendrix, which uses an MPL adjuvant to enhance the immune response. More recently, Dynavax Technologies has been attempting to more effectively vaccinate non-responders with Heplisav, its adjuvanted HBV vaccine candidate, which is in Phase III and preregistration in the US and 5EU, respectively. Clinical trials have demonstrated Heplisav s superior immunogenicity and more convenient dosing regimen, which represent two key advantages over currently marketed products. With Heplisav, Dynavax hopes to address a key clinical unmet need in the treatment landscape, but its commercial success ultimately depends on improving uptake in this segment of the population. GlobalData s primary research has revealed that inadequate hepatitis B vaccination coverage represents one of the most important unmet needs in the global HBV vaccine marketplace. In general, the need for improved vaccine coverage rates is largest outside of routine recommendations, where the vaccination rates for adults with risk factors are poor. Nevertheless, there is still room for improvement even within the context of routine immunization recommendations, which mostly target infants and children. 4
Executive Summary In the pediatric segment of the marketplace, companies are leveraging combination vaccines to increase HBV vaccine uptake, while improved dosing regimens are necessary to increase compliance in adults. For both children and adults, companies must ensure that physicians understand immunization recommendations and are able to effectively identify patients. Overall, GlobalData believes that ensuring high coverage rates will be essential to the commercial success of HBV vaccines for the duration of the forecast period. Established Players and New Entrants Must Effectively Address Gaps in Treatment Algorithm to Achieve Commercial Success The lack of a vaccine that effectively protects all adults, especially persons that do not respond to the currently licensed products, is a glaring unmet need in the treatment algorithm and therefore represents an attractive segment of the market for current players and new entrants alike. With its Phase III vaccine candidate, Heplisav, Dynavax Technologies is attempting to exploit this void in the treatment landscape by utilizing a novel adjuvant to induce a stronger immune response in adults with two doses instead of three. The inclusion of HBV in pediatric combination vaccines is another strategy being leveraged by major players in the marketplace, as many countries see these vaccines as more cost-effective and routinely administer them to infants and toddlers. GlobalData projects that the use of combination vaccines in the eight major markets will only increase over the next several years, so utilizing these vaccines to gain market share will remain a sustainable corporate approach for the entire forecast period. The Pipeline, Led by Dynavax s Heplisav, Will Improve Vaccine Effectiveness in Adults and Stimulate Modest Growth in the Market The prophylactic HBV vaccine market is highly mature, with a small pipeline and clinical trial pool that is poised to address key clinical and environmental unmet needs in the US, 5EU, Japan, and Canada. More specifically, the HBV vaccine pipeline, with Dynavax Technologies Heplisav as the sole late-stage product projected to launch during the forecast period, is heavily focused on the development of more-immunogenic adult vaccines and more conveniently formulated combination vaccines. With Heplisav, Dynavax hopes to leverage its superior immunogenicity and dosing regimen to increase HBV vaccine uptake in the adult marketplace. Sanofi Pasteur MSD s fully liquid pediatric combination vaccine, Hexyon, received EMA approval in 2013 and will also be marketed under the name V419 by Merck in the US and Canada, with projected launch dates of 2015 and 2016, respectively. 5
Executive Summary GlobalData believes that both of these vaccines, despite targeting distinct segments of the market, will have the potential to stimulate solid growth in the global HBV vaccine marketplace, with peakyear sales for Heplisav and Hexyon/V419 projected to reach $85m and $520m, respectively, during the forecast period. Dynavax must address vaccination coverage rate and vaccine awareness concerns if it wishes to fully exploit this market opportunity. Competitive Assessment of Late-Stage Pipeline Agents and Marketed Products in HBV Vaccines, 2012 2022 Commercial Attributes High Low Source: GlobalData. Low Clinical Attributes GSK s Pediarix/ Infanrix Hexa GSK s Fendrix Merck s Recombivax HB Merck s Comvax Kaketsuken s Bimmugen High Merck and Sanofi s Hexyon/V419 GSK s Ambirix/ Twinrix GSK s Engerix-B Dynavax s Heplisav What Do Physicians Think? The KOLs interviewed for this report shared their expert insight into the HBV vaccines market. These KOLs revealed that, while physicians are relatively happy with the performance of the currently marketed vaccines, they realize that there are still glaring weaknesses in the treatment algorithm that must be addressed. They cite increased vaccine immunogenicity in adults as the most important clinical unmet need, and also reveal the need for improved dosing regimens, physician education, and adult immunization strategies. According to the KOLs, combination vaccines are also advantageous for improving vaccination coverage in the pediatric market. Ultimately, KOLs thought that open dialogue between vaccine manufacturers and policymakers is necessary for a vaccine s commercial success in the HBV vaccine market. Yes, I m sure that physicians need to be better educated on how to advise their patients about immunization. OUS key opinion leader, November 2013 A pediatric combination vaccine is more likely to increase vaccine uptake than several vaccines administered separately. OUS key opinion leader, November 2013 I think an ongoing dialogue between policymakers and manufacturers, before vaccines are actually launched, would be beneficial. OUS key opinion leader, October 2013 6
Executive Summary There is a lack of compliance in adults because the series is extended over six months, so it may be difficult to get patients to follow up...the lack of compliance originates from the fact that we cannot get an immune response in less than three doses. US key opinion leader, November 2013 Selectively targeting subgroups within the population has been shown repeatedly for different vaccines to be a very ineffective [immunization] strategy. Doctors and their office staff seemingly have a very hard time in doing that. I mean that s just a fact that s been demonstrated time and time again. US key opinion leader, November 2013 I think there will be a growing trend towards the use of combination vaccines. US key opinion leader, September 2013 A key barrier to increasing vaccine coverage in the adult population is lack of awareness on the part of patients and physicians. US key opinion leader, November 2013 The currently available hepatitis B vaccines require three doses. It would be great to have a vaccine that only requires two doses. I guess it s unreasonable to hope for a vaccine that only requires one [dose], but two doses would be better. US key opinion leader, November 2013 To exploit opportunities, vaccine manufacturers should produce better vaccines, vaccines that have few side effects and are able to raise antibodies levels higher Companies should also be investigating more efficient and cheaper vaccines for development. OUS key opinion leader, November 2013 I think the number one unmet need is the seroconversion problem I would really like a vaccine that induces seroconversion in nearly everybody, if possible everyone I would like a vaccine that would induce in everyone more than 100mIU/mL HBs antibodies. OUS key opinion leader, October 2013 The available hepatitis B vaccines are incredibly safe vaccines, and they are very effective. They are not ideal, there are improvements that we would like to make, and there are also substantial enhancements of hepatitis B immunization programs that are waiting to be undertaken. US key opinion leader, November 2013 7
1 1... 8 1.1 List of Tables... 15 1.2 List of Figures... 20 2 Introduction... 22 2.1 Catalyst... 22 2.2 Related Reports... 23 2.3 Upcoming Related Reports... 24 3 Disease Overview... 25 3.1 Overview... 25 3.2 Etiology and Pathophysiology... 26 3.2.1 Etiology... 26 3.2.2 Pathophysiology... 30 3.3 Symptoms... 32 3.4 Prognosis... 34 4 Vaccination Recommendations and Coverage Rates... 35 4.1 Overview... 35 4.2 US... 38 4.2.1 Immunization Recommendations and Policies... 38 4.2.2 Vaccination Coverage... 40 4.2.3 Clinical Practice... 41 4.3 France... 43 8
4.3.1 Immunization Recommendations and Policies... 43 4.3.2 Vaccination Coverage... 44 4.3.3 Clinical Practice... 46 4.4 Germany... 47 4.4.1 Immunization Recommendations and Policies... 47 4.4.2 Vaccination Coverage... 48 4.4.3 Clinical Practice... 49 4.5 Italy... 51 4.5.1 Immunization Recommendations and Policies... 51 4.5.2 Vaccination Coverage... 52 4.5.3 Clinical Practice... 53 4.6 Spain... 55 4.6.1 Immunization Recommendations and Policies... 55 4.6.2 Vaccination Coverage... 56 4.6.3 Clinical Practice... 57 4.7 UK... 59 4.7.1 Immunization Recommendations and Policies... 59 4.7.2 Vaccination Coverage... 60 4.7.3 Clinical Practice... 61 4.8 Japan... 62 4.8.1 Immunization Recommendations and Policies... 62 4.8.2 Vaccination Coverage... 63 4.8.3 Clinical Practice... 64 9
4.9 Canada... 65 4.9.1 Immunization Recommendations and Policies... 65 4.9.2 Vaccination Coverage... 67 4.9.3 Clinical Practice... 68 5 Competitive Assessment... 70 5.1 Overview... 70 5.2 Strategic Competitor Assessment... 70 5.3 Product Profiles Monovalent Vaccines... 73 5.3.1 Engerix-B... 74 5.3.2 Recombivax HB... 80 5.3.3 Fendrix... 86 5.3.4 Bimmugen... 90 5.4 Product Profiles Combination Vaccines... 92 5.4.1 Infanrix Hexa... 93 5.4.2 Pediarix... 98 5.4.3 Hexyon... 102 5.4.4 Comvax... 108 5.4.5 Twinrix... 113 5.4.6 Ambirix... 118 6 Opportunity and Unmet Need... 123 6.1 Overview... 123 6.2 Increased Vaccine Immunogenicity... 125 6.2.1 Unmet Need... 125 10
6.2.2 Gap Analysis... 127 6.2.3 Opportunity... 128 6.3 Increased Vaccination Coverage Rates... 129 6.3.1 Unmet Need... 129 6.3.2 Gap Analysis... 130 6.3.3 Opportunity... 131 6.4 Increased Patient Awareness... 132 6.4.1 Unmet Need... 132 6.4.2 Gap Analysis... 132 6.4.3 Opportunity... 133 6.5 Improved Physician Education... 134 6.5.1 Unmet Need... 134 6.5.2 Gap Analysis... 135 6.5.3 Opportunity... 135 6.6 More Cost-Effective Vaccines... 137 6.6.1 Unmet Need... 137 6.6.2 Gap Analysis... 137 6.6.3 Opportunity... 138 7 Pipeline Assessment... 139 7.1 Overview... 139 7.2 Clinical Trial Mapping... 140 7.2.1 Clinical Trials by Country... 140 7.2.2 Clinical Trials by Phase and Trial Status... 141 11
7.3 Promising Vaccines in Late-Stage Clinical Development... 143 7.3.1 Heplisav... 145 7.4 Promising Vaccines in Early-Stage Clinical Development... 156 8 Current and Future Players... 158 8.1 Overview... 158 8.2 Trends in Corporate Strategy... 162 8.3 Company Profiles... 164 8.3.1 GSK... 164 8.3.2 Merck... 168 8.3.3 Sanofi... 171 8.3.4 Kaketsuken... 174 8.3.5 Dynavax Technologies... 175 9 Market Outlook... 178 9.1 Global Markets... 178 9.1.1 Forecast... 178 9.1.2 Drivers and Barriers Global Issues... 182 9.2 US... 188 9.2.1 Forecast... 188 9.2.2 Key Events... 192 9.2.3 Drivers and Barriers... 193 9.3 France... 201 9.3.1 Forecast... 201 9.3.2 Key Events... 204 12
9.3.3 Drivers and Barriers... 205 9.4 Germany... 208 9.4.1 Forecast... 208 9.4.2 Key Events... 212 9.4.3 Drivers and Barriers... 213 9.5 Italy... 217 9.5.1 Forecast... 217 9.5.2 Key Events... 220 9.5.3 Drivers and Barriers... 221 9.6 Spain... 224 9.6.1 Forecast... 224 9.6.2 Key Events... 228 9.6.3 Drivers and Barriers... 229 9.7 UK... 231 9.7.1 Forecast... 231 9.7.2 Key Events... 235 9.7.3 Drivers and Barriers... 236 9.7.4 Alternative Market Scenario... 239 9.8 Japan... 239 9.8.1 Forecast... 239 9.8.2 Drivers and Barriers... 242 9.9 Canada... 245 9.9.1 Forecast... 245 13
9.9.2 Key Events... 248 9.9.3 Drivers and Barriers... 249 10 Appendix... 253 10.1 Bibliography... 253 10.2 Abbreviations... 273 10.3 Methodology... 277 10.4 Forecasting Methodology... 277 10.4.1 Patient Populations Targeted for Vaccination... 278 10.4.2 Vaccination Coverage Rates... 281 10.4.3 Vaccinated Patients... 282 10.4.4 Regulatory Approval vs. Advisory Committee Recommendation... 282 10.4.5 Vaccines Included... 283 10.4.6 Key Launch Dates... 284 10.4.7 General Pricing Assumptions... 285 10.4.8 Individual Vaccine Assumptions... 286 10.4.9 Pricing of Pipeline Vaccines... 296 10.5 Physicians and Specialists Included in this Study... 297 10.5.1 Interviews of Key Opinion Leaders (KOLs)... 297 10.5.2 Online Survey of High-Prescribing Physicians (non-kols)... 299 10.6 About the Authors... 300 10.6.1 Analyst... 300 10.6.2 Therapy Area Director... 300 10.6.3 Global Head of Healthcare... 301 14
10.7 About GlobalData... 302 10.8 Disclaimer... 302 1.1 List of Tables Table 1: Modes of HBV Transmission... 31 Table 2: HBV Serological Markers and Test Interpretations... 32 Table 3: Symptoms of HBV Infection... 33 Table 4: HBV Vaccination Advisory Committees by Country... 36 Table 5: HBV Immunization Recommendations by Country... 37 Table 6: Targeted Age Group(s) for Routine Immunization and Most Administered HBV Vaccines by Country in the Global Markets, 2014... 38 Table 7: Targeted Age Group(s) for Routine HBV Immunization in Canada, by Province or Territory, 2014... 67 Table 8: Leading Vaccines for HBV, 2014... 73 Table 9: Product Profile Engerix-B... 75 Table 10: Immunogenicity Profile Engerix-B... 76 Table 11: Safety Profile Engerix-B... 77 Table 12: Engerix-B SWOT Analysis, 2014... 78 Table 13: Global Sales Forecasts ($m) for Engerix-B, 2012 2022... 79 Table 14: Product Profile Recombivax HB... 81 Table 15: Immunogenicity Profile Recombivax HB... 82 Table 16: Safety Profile Recombivax HB... 83 Table 17: Recombivax HB SWOT Analysis, 2014... 84 Table 18: Global Sales Forecasts ($m) for Recombivax HB, 2012 2022... 85 Table 19: Product Profile Fendrix... 87 15
Table 20: Immunogenicity Profile Fendrix... 88 Table 21: Safety Profile Fendrix... 88 Table 22: Fendrix SWOT Analysis, 2014... 89 Table 23: Global Sales Forecasts ($m) for Fendrix, 2012 2022... 90 Table 24: Product Profile Bimmugen... 91 Table 25: Bimmugen SWOT Analysis, 2014... 91 Table 26: Global Sales Forecasts ($m) for Bimmugen, 2012 2022... 92 Table 27: Product Profile Infanrix Hexa... 94 Table 28: Immunogenicity Profile Infanrix Hexa... 95 Table 29: Safety Profile Infanrix Hexa... 96 Table 30: Infanrix Hexa SWOT Analysis, 2014... 96 Table 31: Global Sales Forecasts ($m) for Infanrix Hexa, 2012 2022... 97 Table 32: Product Profile Pediarix... 99 Table 33: Immunogenicity Profile Pediarix... 100 Table 34: Safety Profile Pediarix... 100 Table 35: Pediarix SWOT Analysis, 2014... 101 Table 36: Global Sales Forecasts ($m) for Pediarix, 2012 2022... 102 Table 37: Product Profile Hexyon... 104 Table 38: Immunogenicity Profile Hexyon... 105 Table 39: Safety Profile Hexyon... 106 Table 40: Hexyon SWOT Analysis, 2014... 106 Table 41: Global Sales Forecasts ($m) for Hexyon, 2012 2022... 108 Table 42: Product Profile Comvax... 109 Table 43: Immunogenicity Profile Comvax... 110 16
Table 44: Safety Profile Comvax... 111 Table 45: Comvax SWOT Analysis, 2014... 111 Table 46: Global Sales Forecasts ($m) for Comvax, 2012 2022... 112 Table 47: Product Profile Twinrix... 114 Table 48: Immunogenicity Profile Twinrix... 115 Table 49: Safety Profile Twinrix... 116 Table 50: Twinrix SWOT Analysis, 2014... 117 Table 51: Global Sales Forecasts ($m) for Twinrix, 2012 2022... 118 Table 52: Product Profile Ambirix... 119 Table 53: Immunogenicity Profile Ambirix... 120 Table 54: Safety Profile Ambirix... 121 Table 55: Ambirix SWOT Analysis, 2014... 121 Table 56: Global Sales Forecasts ($m) for Ambirix, 2012 2022... 122 Table 57: Unmet Need and Opportunity in Prophylactic HBV Vaccines... 125 Table 58: HBV Vaccines Clinical Trials by Phase and Status, 2014... 142 Table 59: HBV Vaccines Phase Pipeline, 2014... 143 Table 60: Comparison of Vaccines in Development for HBV, 2014... 144 Table 61: Product Profile Heplisav... 147 Table 62: Immunogenicity Profile Heplisav... 148 Table 63: Safety Profile Heplisav... 150 Table 64: Heplisav SWOT Analysis, 2014... 154 Table 65: Global Sales Forecasts ($m) for Heplisav, 2012 2022... 156 Table 66: Key Companies in the HBV Vaccine Market, 2014... 160 Table 67: GSK s HBV Vaccine Portfolio Assessment, 2014... 166 17
Table 68: GSK SWOT Analysis, 2014... 167 Table 69: Merck s HBV Vaccine Portfolio Assessment, 2014... 169 Table 70: Merck SWOT Analysis, 2014... 170 Table 71: Sanofi s HBV Vaccine Portfolio Assessment, 2014... 172 Table 72: Sanofi SWOT Analysis, 2014... 173 Table 73: Kaketsuken s HBV Vaccine Portfolio Assessment, 2014... 174 Table 74: Kaketsuken SWOT Analysis, 2014... 175 Table 75: Dynavax Technologies HBV Vaccine Portfolio Assessment, 2014... 176 Table 76: Dynavax Technologies SWOT Analysis, 2014... 177 Table 77: Global Sales Forecasts ($m) for HBV Vaccines, 2012 2022... 180 Table 78: Global HBV Vaccine Market Drivers and Barriers, 2014... 182 Table 79: Sales Forecasts ($m) for HBV Vaccines in the United States, 2012 2022... 190 Table 80: Key Events Impacting Sales for HBV Vaccines in the United States, 2014... 192 Table 81: United States HBV Vaccine Market Drivers and Barriers, 2014... 193 Table 82: Sales Forecasts ($m) for HBV Vaccines in France, 2012 2022... 202 Table 83: Key Events Impacting Sales for HBV Vaccines in France, 2014... 204 Table 84: France HBV Vaccine Market Drivers and Barriers, 2014... 205 Table 85: Sales Forecasts ($m) for HBV Vaccines in Germany, 2012 2022... 210 Table 86: Key Events Impacting Sales for HBV Vaccines in Germany, 2014... 212 Table 87: Germany HBV Vaccine Market Drivers and Barriers, 2014... 213 Table 88: Sales Forecasts ($m) for HBV Vaccines in Italy, 2012 2022... 218 Table 89: Key Events Impacting Sales for HBV Vaccines in Italy, 2014... 220 Table 90: Italy HBV Vaccine Market Drivers and Barriers, 2014... 221 Table 91: Sales Forecasts ($m) for HBV Vaccines in Spain, 2012 2022... 226 18
Table 92: Key Events Impacting Sales for HBV Vaccines in Spain, 2014... 228 Table 93: Spain HBV Vaccine Market Drivers and Barriers, 2014... 229 Table 94: Sales Forecasts ($) for HBV Vaccines in the United Kingdom, 2012 2022... 233 Table 95: Key Events Impacting Sales for HBV Vaccines in the United Kingdom, 2014... 235 Table 96: United Kingdom HBV Vaccine Market Drivers and Barriers, 2014... 236 Table 97: Sales Forecasts ($) for HBV Vaccines in Japan, 2012 2022... 240 Table 98: Japan HBV Vaccine Market Drivers and Barriers, 2014... 242 Table 99: Sales Forecasts ($) for HBV Vaccines in Canada, 2012 2022... 246 Table 100: Key Events Impacting Sales for HBV Vaccines in Canada, 2014... 248 Table 101: Canada HBV Vaccine Market Drivers and Barriers, 2014... 249 Table 102: Patient Population(s) Targeted for HBV Vaccination in the Pediatric Market, by Country... 279 Table 103: Patient Population(s) Targeted for HBV Vaccination in the Adult Market, by Country... 280 Table 104: Key Launch Dates... 284 Table 105: High-Prescribing Physicians (non-kols) Surveyed, by Country... 299 19
1.2 List of Figures Figure 1: HBV Structure and the Recombinant Vaccine Development Process... 27 Figure 2: Routine HBV Vaccination Coverage (%) in the United States... 41 Figure 3: High-Prescriber Estimation of Pediatric HBV Vaccine Patient Share in the United States, 2014... 42 Figure 4: Routine HBV Vaccination Coverage (%) in France... 45 Figure 5: High-Prescriber Estimation of Pediatric HBV Vaccine Patient Share in France, 2014... 47 Figure 6: Routine HBV Vaccination Coverage (%) in Germany... 49 Figure 7: High-Prescriber Estimation of Pediatric HBV Vaccine Patient Share in Germany, 2014... 50 Figure 8: Routine HBV Vaccination Coverage (%) in Italy... 53 Figure 9: High-Prescriber Estimation of Pediatric HBV Patient Share in Italy, 2014... 54 Figure 10: Routine HBV Vaccination Coverage (%) in Spain... 57 Figure 11: High-Prescriber Estimation of Pediatric HBV Vaccine Patient Share in Spain, 2014... 58 Figure 12: High-Prescriber Estimation of Pediatric HBV Vaccine Patient Share in the United Kingdom, 2014. 62 Figure 13: High-Prescriber Estimation of Pediatric HBV Vaccine Patient Share in Japan, 2014... 65 Figure 14: High-Prescriber Estimation of Pediatric HBV Vaccine Patient Share in Canada, 2014... 69 Figure 15: HBV Vaccines Clinical Trials by Country, 2014... 141 Figure 16: Competitive Assessment of Late-Stage Pipeline Agents and Marketed Products in HBV Vaccines, 2012 2022... 144 Figure 17: Global Sales for HBV Vaccines by Company, 2012 2022... 161 Figure 18: Company Portfolio Gap Analysis in HBV Vaccines, 2012 2022... 162 Figure 19: Global Sales for HBV Vaccines by Country, 2012 2022... 181 Figure 20: Sales for HBV Vaccines in the United States by Vaccine, 2012 2022... 191 Figure 21: Sales for HBV Vaccines in France by Vaccine, 2012 2022... 203 Figure 22: Sales for HBV Vaccines in Germany by Vaccine, 2012 2022... 211 20
Figure 23: Sales for HBV Vaccines in Italy by Vaccine, 2012 2022... 219 Figure 24: Sales for HBV Vaccines in Spain by Vaccine, 2012 2022... 227 Figure 25: Sales for HBV Vaccines in the United Kingdom by Vaccine, 2012 2022... 234 Figure 26: Sales for HBV Vaccines in Japan by Vaccine, 2012 2022... 241 Figure 27: Sales for HBV Vaccines in Canada by Vaccine, 2012 2022... 247 21
Introduction 2 Introduction 2.1 Catalyst The global (7MM and Canada) prophylactic hepatitis B virus (HBV) vaccine market has seen moderate growth over the last several years, primarily due to the effectiveness of routine childhood immunization programs and the strong clinical performance of currently marketed vaccines, such as GSK s Engerix-B, Pediarix/Infanrix Hexa, and Merck s Recombivax HB, in these targeted populations. Despite this success, opportunities still exist for improving the treatment algorithm. The growing popularity of combination vaccines, along with the push for vaccines that achieve higher seroconversion in non-responders, will serve to stimulate modest growth in the marketplace over the forecast period from 2012 2022. GlobalData expects the following key factors to contribute to the evolution of the prophylactic HBV vaccine market over the next decade: The maintenance and/or increase of routine HBV vaccination coverage rates in the 7MM and Canada will be essential to the commercial success of these vaccines, as widespread uptake outside of official recommendations is unlikely. GlobalData believes that country-specific immunization recommendations and policy implementation will be an essential metric for determining future vaccine uptake. Our report provides a detailed, primary research-driven analysis of immunization policy at the country level. Vaccines that more effectively protect traditional non-responders, such as patients with chronic kidney disease (CKD) and diabetes mellitus, have the potential to address an area of high unmet need while simultaneously exploiting a largely untapped segment of the HBV vaccine market. For example, Dynavax s Heplisav has showed encouraging results in Phase III clinical studies in the US. Key opinion leaders (KOLs) have indicated to GlobalData that, despite superior clinical performance, the success of vaccines targeting these specific adult populations will depend upon a drastic improvement in current coverage rates. 22
Introduction A growing preference for pediatric combination vaccines, particularly in the 5EU, is expected to drive stiff competition between GSK s Infanrix Hexa and Sanofi Pasteur MSD s Hexyon. Vaccine manufacturers will focus much effort on emphasizing the convenience and costeffectiveness of combination vaccines, but their eventual use will depend heavily on how well they fit into country-specific vaccination schedules. Our report includes a thorough competitive assessment of marketed and late-stage pipeline vaccines in the 7MM and Canada, which takes into account both clinical and commercial positioning. GlobalData anticipates that vaccine manufacturers will face an uphill battle in countries that do not currently recommend routine vaccination against HBV, such as the UK and Japan. Despite pressure from patient advocacy and pro-immunization groups, KOLs have indicated that shortterm change to immunization policy appears unlikely. Firms interested in accessing these markets may only target specific at-risk patient populations for the foreseeable future. 2.2 Related Reports GlobalData (2013). PharmaPoint: HIV Therapeutics Global Drug Forecast and Market Analysis to 2022: Event-Driven Update, March, 2013, GDHC41PIDR GlobalData (2013). PharmaFocus: Vaccine Adjuvants in Infectious Disease, March, 2013, GDHC001PFR GlobalData (2013). PharmaPoint: Pediatric Respiratory Syncytial Virus Prophylactics United States Drug Forecast and Market Analysis to 2022, April, 2013, GDHC102PIDR GlobalData (2013). PharmaPoint: HCV Therapeutics Global Drug Forecast and Market Analysis to 2022, May, 2013, GDHC42PIDR GlobalData (2013). PharmaPoint: Dermatophytic Onychomycosis United States Drug Forecast and Market Analysis to 2022, June, 2013, GDHC101PIDR GlobalData (2013). PharmaPoint: Meningococcal Vaccines Global Drug Forecast and Market Analysis to 2022, June 2013, GDHC51PIDR GlobalData (2013). PharmaFocus: Market Access Strategies for Antibiotics Targeting Multidrug-Resistant Gram-Negative Bacteria, August 2013, GDHC004PFR 23
Introduction GlobalData (2013). PharmaFocus: HIV R&D Strategies Towards Cure and Prevention, August 2013, GDHC003PFR GlobalData (2013). PharmaPoint: Meningococcal Vaccines Global Drug Forecast and Market Analysis to 2022: Event-Driven Update, August 2013, GDHC61PIDR GlobalData (2013). PharmaPoint: Seasonal Influenza Vaccines Global Drug Forecast and Market Analysis to 2022: Event-Driven Update, September 2013, GDHC67PIDR 2.3 Upcoming Related Reports GlobalData (2014). PharmaPoint: Asthma Therapeutics Global Drug Forecast and Market Analysis to 2022, March 2014, GDHC75PIDR. GlobalData (2014). PharmaPoint: Prophylactic HPV Vaccines Global Drug Forecast and Market Analysis to 2022, February 2014, GDHC84PIDR. 24
Appendix 10.7 About GlobalData GlobalData is a leading global provider of business intelligence in the Healthcare industry. GlobalData provides its clients with up-to-date information and analysis on the latest developments in drug research, disease analysis, and clinical research and development. Our integrated business intelligence solutions include a range of interactive online databases, analytical tools, reports and forecasts. Our analysis is supported by a 24/7 client support and analyst team. GlobalData has offices in New York, Boston, San Francisco, London, India and Singapore. 10.8 Disclaimer All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher, GlobalData. 302