REFERENCE CODE GDHC93PIDR PUBLICATION DATE DECEM BER 2014 RHEUMATOID ARTHRITIS GLOBAL DRUG FORECAST AND MARKET ANALYSIS TO 2023
Executive Summary The table below summarizes the key metrics for rheumatoid arthritis (RA) in the seven major pharmaceutical markets analyzed in this report: the US, France, Germany, Italy, Spain, the UK, and Japan. Additional markets covered in this report include Australia, China, and India, for a total of 10 major markets (10MM) during the forecast period from 2013 2023. Rheumatoid Arthritis: Key Metrics in the 10 Major Pharmaceutical Markets 2013 Epidemiology Prevalent Population Diagnosed Prevalence Population Treated Population 2013 Market Sales US 5EU Japan Australia China India Total Pipeline Assessment 12.9 million 7.3 million 5.3 million $10.4bn $2.9bn $969.7m $476.9m $325.8m $529.7m $15.6bn Number of drugs in Phase IIa 43 Number of drugs in Phase IIb III (late-stage development) Number of first-in-class drugs (late-stage development) Most Promising Pipeline Drugs Adalimumab biosimilars Infliximab biosimilars Mavrilimumab Sirukumab Baricitinib Key Events (2013 2023) Launch of biosimilars for several established brands (10MM) 13 5 Peak-Year Sales $1,978.2m $815.3m $366.3m $212.3m $112.5m Level of Impact Launch of sirukumab (10MM) Launch of baricitinib (10MM) Launch of mavrilimumab (US, 5EU) 2023 Market Sales US 5EU Japan Australia China India Total Source: GlobalData 10MM = US, France, Germany, Italy, Spain, UK, Japan, Australia, China, and India 5EU = France, Germany, Italy, Spain, and UK $12.6bn $3.6bn $1.2bn $613.8m $588.9m $780.0m $19.3bn Steady Growth in the RA Market Expected from 2013 to 2023 The RA market in the 10MM (US, France, Italy, Germany, Spain, UK, Australia, China, and India) is expected to grow at a Compound Annual Growth Rate (CAGR) of 2.1% during the forecast period, from 2013 sales of $15.6 billion to sales of $19.3 billion in 2023. The major drivers of growth in the global RA market during the forecast period are: An increase in the prevalent cases of RA in all the markets, in part, due to an aging population 2
Executive Summary The anticipated introduction of interleukin (IL)-6 inhibitors (Sanofi/Regeneron s sarilumab, Johnson & Johnson/GlaxoSmithKline s [J&J/GSK s] sirukumab, Alder s clazakizumab), novel biologics (Novartis Cosentyx, AstraZeneca/MedImmune s mavrilimumab, AbbVie/Biotest s tregalizumab, and Amgen/Daiichi Sankyo s denosumab), small molecules (four janus kinase [JAK] inhibitors: Eli Lilly/Incyte s baricitinib, Astellas peficitinib, Vertex s decernotinib, AbbVie/Galapagos filgotinib; and one c-kit inhibitor: AB Science s masitinib), which will expand options to treat RA patients and contribute to overall market growth The early diagnosis and treatment of patients with RA to limit disease progression The market entry of biosimilars, which will make RA treatments more accessible The major barriers to the growth of the global RA market during the forecast period are: The high cost of biologics, which will limit their uptake, especially in cost-conscious markets that are facing austerity measures The lack of regulatory guidance on biosimilars The market entry of biosimilars, which will provide a less expensive alternative and will challenge the established brands The figure below shows the sales for RA in the 10MM by region during the forecast period. Sales for RA by Region, 2013 2023 3% 2% 8% 2% 4% 2% 4% 3% 8% 2% 6% 6% 2% 3% 3% 3% 4% 3% 67% 65% US France Germany Italy Spain UK Japan Australia China India Source: GlobalData 2013 Total: $15.6bn 2023 Total: $19.3bn 3
Executive Summary The RA Market is Dominated by Big Pharma, Biologics, and High Price Tags The RA market is dominated by Big Pharma, and all of the compounds in late-stage development are backed by a major pharmaceutical company. The major players in the RA market have extensive portfolios, and may enter into Phase I buyouts and partnerships at very early stages. It is especially common for these companies to form an early partnership for development in the Japanese market: for example, AstraZeneca/MedImmune s partnership with Daiichi Sankyo on the Phase I biologic known as AMP-110. Increasingly, due to the fragmented and increasingly competitive landscape, companies are favoring collaborations in order to overcome both R&D and commercial barriers, reducing both their risk and costs in the process. For example, Regeneron has partnered with Sanofi for the Phase III IL-6 inhibitor, sarilumab. It is also common for Big Pharma to team up together and leverage their positions in the global markets, as is the case with sirukumab, an IL-6 inhibitor backed by both J&J and GSK. While the development of biologics is both a difficult and expensive endeavor, pharmaceutical companies have used it to their advantage. The pricing for these RA drugs is upwards of $30,000 per year, and although the market is crowded, a small patient share often translates into big earnings. Pfizer used this pricing strategy to its advantage when Xeljanz (tofacitinib) launched in the US in 2012 and in Japan in 2013. At that time, there were no oral disease-modifying antirheumatic drugs (DMARDs) on the market to compete with the biologics, so Pfizer priced its small molecule close to that of a biologic agent. Since the pathophysiology of RA overlaps with that of other inflammatory diseases, most RA drugs will undergo label expansions into additional indications, such as ankylosing spondylitis, psoriasis, psoriatic arthritis, systemic lupus erythematosus, and ulcerative colitis. However, the major brands for RA will soon face patent expiration, and biosimilars will be available in all 10 markets covered in this report by the conclusion of the forecast period in 2023. Biosimilars alone are forecast at $4.6 billion for the 2023 RA market, with adalimumab biosimilars accounting for nearly half that number at $2 billion. Meanwhile, a strategy being utilized by Roche, another key player in the RA market, is to strengthen its brand, and the company is currently running several post-marketing trials for Actemra (tocilizumab) to establish the drug s position within the treatment paradigm. Several Big Pharma companies, such as Pfizer and Amgen, have realized the potential of biosimilars in the RA market and have launched programs to develop biosimilars of their own. 4
Executive Summary The figure below provides an analysis of the company portfolio gap in RA during the forecast period. Company Portfolio Gap Analysis in RA, 2013 2023 Strength of Marketed Products High Low Source: GlobalData Current Players Low Strength of Pipeline Current and Future Players Future Players High Biomarkers and Biosimilars Hold Hope in Addressing Unmet Needs in RA The biologic agents available to treat RA are reasonably effective at managing the symptoms and preventing progression of the disease. However, the challenges in treating the disease lie in the unpredictable responses of each patient. Many patients become frustrated as they cycle through multiple biologic agents before finding one that is effective at managing their disease. Key opinion leaders (KOLs) interviewed by GlobalData hope that research on RA moves towards individualized medicine, and that predictive biomarkers will one day be available to determine the best course of action to take for each patient. At the same time, it is recognized that RA may be a heterogeneous group of diseases, and that each subtype may have a predominant pathway that is pathologically altered. A key concern is that the prohibitive cost of the biologics means that some patients are unable to afford these medications, or that governments must limit the number of patients who are approved for them. With biosimilars priced at 70% the cost of the originator brand, the addition of these therapies to the RA market will certainly make treatment more accessible. However, KOLs interviewed by GlobalData believe that the lower cost of biosimilars will not completely address the need for less expensive treatment options. Pipeline Drugs Will Only Partially Address the Remaining Unmet Needs in RA The unmet needs in RA are not expected to be directly addressed by the pipeline agents. The disease is effectively treated by the currently available options, and upon launch, the pipeline agents will compete for the same patient populations. Although drugs with novel mechanisms of action are welcome additions to the market, the real challenge will be to determine where these drugs fit into the treatment paradigm. The unmet needs are likely to be met through initiatives and research efforts to understand the pathophysiology of RA, and through the development of diagnostic and prognostic 5
Executive Summary biomarkers for the disease. These efforts are likely to expand the RA market through the diagnosis of patients as early as possible, and by targeting the correct therapy to each patient. While research in this area is underway, it is expected that individualized medicine will still be in its beginning stages by the end of the forecast period in 2023. Due to the competitive nature of the RA market, pipeline agents must meet a number of criteria. The drugs must be both safe and effective, and ideally, be provided at a lower cost than the currently available therapies. Pfizer s Xeljanz, the first oral therapy to compete with the biologics in the RA market, which launched in the US in 2012 and in Japan in 2013, is priced higher than most oral medications, as the current market allows for high prices. This scenario will likely change by 2021, when Xeljanz loses its patent protection expiration in the US, and the first JAK inhibitor is offered as a generic. However, the situation will be different from the patent expiration of biologics, where biosimilars must go through an expensive development program, including Phase I and Phase III testing, and as a result, these products are likely to be priced high. Biologics and Small Molecules with Novel Mechanisms of Action are Welcome Additions to the RA Market The late-stage pipeline for RA contains both nonanti-tumor necrosis factor (TNF) biologics and novel oral therapies for RA. Of the seven current late-stage biologics, most target inflammatory pathways, and include three anti-il6 therapies (Sanofi/Regeneron s sarilumab, J&J/GSK s sirukumab, Alder s clazakizumab), an anti-il17 (Novartis Cosentyx), and two drugs with novel mechanisms of action that target immune cells (AstraZeneca-MedImmune s mavrilimumab and AbbVie/Biotest s tregalizumab). Additionally, Amgen/Daiichi Sankyo s denosumab, which is a marketed drug for bone disorders that targets receptor activator nuclear factor kappa-b ligand (RANKL), a molecule in the TNF family that controls bone resorption, is expected to gain label expansion for RA in Japan. There are also two classes of oral therapies in the late-stage RA pipeline, including four JAK inhibitors (Eli Lilly/Incyte s baricitinib, AbbVie/Galapagos filgotinib, Astellas peficitinib, and Vertex s decernotinib), and one c-kit inhibitor (AB Science s masitinib). The key products that are expected to have the largest impact on the global RA market include: J&J and GSK s sirukumab, which is in Phase III of development and is expected to launch in all the markets in 2018, with the exception of China, where it will launch in 2022. Although sirukumab is considered to have a safety and efficacy similar to sarilumab, and will launch in the same year, it is expected to become available in all the markets and have higher sales. Sirukumab is expected to reach annual sales of $212.3m in 2023, and will primarily 6
Executive Summary compete with Roche s IL-6 inhibitor, Actemra (SC). Eli Lilly and Incyte s baricitinib is a Phase III oral JAK inhibitor. Although it will face competition in the US and Japan, baricitinib is expected to be the first available JAK inhibitor in the 5EU, Australia, China, and India, with its launch forecast to occur in 2017, with the exception of China, where it will launch in 2021. Still, this assumption is based on the current unclear status and future of Pfizer s Xeljanz in the 5EU, following a negative recommendation from the European Medicine Agency s (EMA s) Committee for Medicinal Products for Human Use (CHMP) for the drug in 2013. Sales of baricitinib are forecast at $112.5m in 2023, and the drug will cover more markets than the other JAK inhibitors in the pipeline. AstraZeneca/MedImmune s Phase IIb drug, mavrilimumab, is a monoclonal antibody (mab) targeted against the granulocyte macrophage colony-stimulating factor (GM-CSF) receptor and reduces inflammation in the joints. Although mavrilimumab will likely be reserved at least as a second line of biologic therapy, it is highly anticipated as the first drug of its class, with no drugs in the pipeline of the same class. Mavrilimumab is expected to launch in 2020, and is anticipated to reach annual sales of $366.3m in 2023. Biotest and AbbVie s tregalizumab is a Phase IIb mab directed at the CD4 receptor on regulatory T cells (Tregs), and activates this cell type, limiting inflammation. Like mavrilimumab, this drug will be a first-in-class agent, with no other drugs in the pipeline having the same mechanism of action, and will likely be used in a similar clinical setting, as it will be reserved as a second-line biologic therapy, or beyond. Tregalizumab is expected to launch in 2022, with sales reaching approximately $161.6m the following year. The figure below provides a competitive assessment of the most promising late-stage pipeline agents for RA during the forecast period. Competitive Assessment of the Late-Stage Pipeline Agents for RA, 2013 2023 Commercial Attributes High Low Novartis s Cosentyx Amgen/Daiichi Sankyo s denosumab IRBP s RAVAX Source: GlobalData Low Astellas s pef icitinib Clinical Attributes Lilly/Incyte s baricitinib Galapagos/AbbVie s filgotinib Biotest/AbbVie s Vertex s tregalizumab decernotinib AB Science s masitinib High J&J/GSK s sirukumab Sanofi/Regeneron s sarilumab Alder s clazakizumab AstraZeneca s mavrilimumab 7
Executive Summary What Do Physicians Think? The RA market is very competitive, and the new entrants are expected to be met with some resistance and experience slow uptake, as the market is currently dominated by the anti-tnfs, and rheumatologists feel comfortable with the longterm safety and efficacy of this class of drugs. We at least have a reasonably good handle on what the long-term or relatively long-term safety profile of [the] anti-tnfs is. They re not perfect, but at least we know what the issues are, and there are concerns, I think, with the [the] long-term safety profiles of some of the new agents that have come through. And so, given that we rheumatologists feel more comfortable with the anti-tnfs, we know what to look out for. Then, for any new players, it can be difficult to compete because the concern is always, well, maybe the new drug might have long-term side effects, and so we better use the ones that we ve got more [that] we re more familiar with. [EU] KOL Unless we can upfront identify a group in whom it s [a pipeline agent] going to be effective, [or] unless it s marketed at a significantly lower cost than its competitors, what will happen is that the [new] drug will be used fourth or fifth line, etcetera. Because if it costs the same as a currently available biologic, the currently available biologics have got a stronger history, [a] longer history of maybe safety and efficacy data, [so] why would you choose to use the new one unless you d actually tried and failed [with] the old ones? The problem with that, of course, for the new ones, is that they end up being tried on often the most difficult rheumatoid [arthritis] patients, and so, often they don t work. [EU] KOL One of the greatest challenges with the introduction of new biologics in the RA market will be to target these drugs to the right patients. Many rheumatologists believe that the future of RA is in individualized medicine, where biomarkers determine the best course of action for each patient. 8
Executive Summary I think the patients find the whole process [of finding an effective therapy to be] very difficult. They often lose faith in our approach to treat their disease well. It may have an impact on their adherence to medication in the future. We kind of keep dropping and changing between one thing and another thing. How do they know that the fifth thing is going to work when the first four haven t? Actually, adherence to drugs is a big issue in people with long-term conditions [such as RA], and the fact that it can take us a long time to find something that works, I think, is a big issue in the context of that for the patients as well. [UK] KOL I think it will be very difficult for rheumatologists to manage this huge number of different drugs that are available without us having some kind of strategy for establishing which groups of patients each particular drug would be most effective in, and so that kind of takes us down to [the] personalized medicine route, and I think that s what companies need to be looking at as they re developing these new agents.we need to work out who to treat with what who to treat with what drug, based on identifying biomarkers that predict [the patient s] response, which could be ones that you measure in the blood or [the] ones that you measure from the joint, but I think that will have to be the direction of travel. One of the greatest unmet needs in RA is the affordability of drugs, as the biologics cost upwards of $30,000 per year in the US. Biosimilars are expected to launch over the forecast period from 2013 2023 in all 10 markets covered in this report, changing the market dynamics and offering a less expensive alternative to the branded biologics. If a biosimilar is only half as expensive [as the originator brand] which it s probably not, [as that s] probably overly optimistic it s still way out of the reach of most patients if they have [health insurance] coverage problems. Yes, it will help the overall system, but [it will] probably not help the individual patient very much. [I would prescribe biosimilars when they are available] sure, absolutely.you would potentially replace the innovative product with a biosimilar whenever you have that option. The only reason you do that, obviously, is cost. In most cases, it s not going to be my decision; it s going to be the decision of whoever is paying for it.it will be helpful, but it s not going to be a big game-changer.two thirds of [what is already] a heck of a lot of money is still almost a heck of a lot of money, and most people don t have that. [US] KOL [EU] KOL 9
1 1... 10 1.1 List of Tables... 17 1.2 List of Figures... 25 2 Introduction... 28 2.1 Catalyst... 28 2.2 Related Reports... 29 2.3 Upcoming Related Reports... 29 3 Disease Overview... 30 3.1 Etiology and Pathophysiology... 30 3.1.1 Etiology... 30 3.1.2 Pathophysiology... 30 3.2 Symptoms... 35 3.3 Prognosis... 35 3.4 Quality of Life... 36 4 Epidemiology... 37 4.1 Disease Background... 37 4.2 Risk Factors and Comorbidities... 37 4.3 Global Trends... 39 4.3.1 US... 39 4.3.2 5EU... 40 4.3.3 Japan... 41 4.3.4 Australia... 41 4.3.5 China... 42 4.3.6 India... 42 4.4 Forecast Methodology... 42 4.4.1 Sources Used... 45 10
4.4.2 Sources Not Used... 49 4.4.3 Forecast Assumptions and Methods Total Prevalent Cases of RA... 50 4.4.4 Forecast Assumptions and Methods Diagnosed Prevalent Cases of RA... 54 4.5 Epidemiological Forecast for RA (2013 2023)... 55 4.5.1 Total Prevalent Cases of RA... 55 4.5.2 Age-Specific Total Prevalent Cases of RA... 57 4.5.3 Sex-Specific Total Prevalent Cases of RA... 59 4.5.4 Diagnosed Prevalent Cases of RA... 61 4.5.5 Age-Standardized Diagnosed Prevalence of RA... 63 4.6 Discussion... 64 4.6.1 Epidemiological Forecast Insight... 64 4.6.2 Limitations of the Analysis... 65 4.6.3 Strengths of the Analysis... 66 5 Disease Management... 67 5.1 Diagnosis and Treatment Overview... 67 5.1.1 Diagnosis... 67 5.1.2 Treatment Guidelines... 69 5.1.3 Leading Prescribed Drugs for the Treatment of RA... 78 5.1.4 Clinical Practice... 79 5.2 US... 84 5.3 France... 88 5.4 Germany... 89 5.5 Italy... 92 5.6 Spain... 94 5.7 UK... 95 5.8 Japan... 99 5.9 Australia... 101 11
5.10 China... 103 5.11 India... 105 6 Competitive Assessment... 108 6.1 Overview... 108 6.2 Product Profiles Major Brands... 109 6.2.1 Enbrel (etanercept)... 109 6.2.2 Humira (adalimumab)... 116 6.2.3 Remicade (infliximab)... 120 6.2.4 Simponi (golimumab)... 126 6.2.5 Cimzia (certolizumab pegol)... 132 6.2.6 Orencia (abatacept)... 136 6.2.7 Actemra/RoActemra (tocilizumab)... 142 6.2.8 Rituxan/MabThera (rituximab)... 150 6.2.9 Inflectra/Remsima (infliximab biosimilar)... 155 6.2.10 Xeljanz (tofacitinib)... 158 6.2.11 Iguratimod/T-614... 165 6.2.12 Methotrexate (Numerous Brands)... 168 6.3 Biosimilars... 172 6.3.1 Introduction... 172 6.3.2 Hospira s Inflectra Versus J&J s Remicade in Key Autoimmune Diseases... 174 6.3.3 Biosimilars in the Immunology Community... 174 6.3.4 By the Numbers: Biosimilars in Development... 175 6.3.5 The Impact of Biosimilars Will be Felt Throughout the Pharmaceutical Industry... 179 6.3.6 Uptake of Biosimilars for RA is Expected to Vary by Market... 180 6.3.7 Biosimilars Forecast... 183 6.4 Other Therapies... 191 7 Unmet Need and Opportunity... 193 12
7.1 Overview... 193 7.2 Development of Cost-Effective Therapies... 194 7.2.1 Unmet Need... 194 7.2.2 Gap Analysis... 195 7.2.3 Opportunity... 195 7.3 Biomarkers to Predict Responsiveness to Therapy... 195 7.3.1 Unmet Need... 195 7.3.2 Gap Analysis... 197 7.3.3 Opportunity... 198 7.4 Early Diagnosis of RA... 198 7.4.1 Unmet Need... 198 7.4.2 Gap Analysis... 199 7.4.3 Opportunity... 200 7.5 Personalized Treatment Approach... 201 7.5.1 Unmet Need... 201 7.5.2 Gap Analysis... 201 7.5.3 Opportunity... 203 8 Pipeline Assessment... 205 8.1 Overview... 205 8.2 Clinical Trial Mapping... 205 8.2.1 Clinical Trials by Class... 205 8.3 Promising Drugs in Clinical Development... 207 8.3.1 Sarilumab... 214 8.3.2 Sirukumab... 222 8.3.3 Clazakizumab... 229 8.3.4 Cosentyx (secukinumab)... 235 8.3.5 Tregalizumab... 241 13
8.3.6 Mavrilimumab... 247 8.3.7 Denosumab (Prolia/Xgeva)... 252 8.3.8 Baricitinib... 258 8.3.9 Peficitinib... 268 8.3.10 Decernotinib... 274 8.3.11 Filgotinib... 280 8.3.12 Masitinib... 286 8.3.13 RAVAX... 293 8.4 Other Drugs in Development... 298 9 Current and Future Players... 301 9.1 Trends in Corporate Strategy... 304 9.2 Company Profiles... 305 9.2.1 AbbVie... 305 9.2.2 Pfizer... 307 9.2.3 Amgen... 310 9.2.4 Johnson & Johnson... 313 9.2.5 Eli Lilly... 315 9.2.6 Bristol-Myers Squibb... 317 9.2.7 UCB... 319 9.2.8 Roche... 320 9.2.9 GlaxoSmithKline... 322 9.2.10 Novartis... 324 9.2.11 Sanofi... 326 9.2.12 AstraZeneca- MedImmune... 328 9.2.13 Astellas... 330 9.2.14 Vertex... 332 9.2.15 Daiichi Sankyo... 334 14
10 Market Outlook... 337 10.1 Global Markets... 337 10.1.1 Forecast... 337 10.1.2 Drivers and Barriers Global Issues... 342 10.2 United States... 344 10.2.1 Forecast... 344 10.2.2 Key Events... 350 10.2.3 Drivers and Barriers... 351 10.3 France... 353 10.3.1 Forecast... 353 10.3.2 Key Events... 358 10.3.3 Drivers and Barriers... 358 10.4 Germany... 361 10.4.1 Forecast... 361 10.4.2 Key Events... 366 10.4.3 Drivers and Barriers... 367 10.5 Italy... 370 10.5.1 Forecast... 370 10.5.2 Key Events... 375 10.5.3 Drivers and Barriers... 375 10.6 Spain... 377 10.6.1 Forecast... 377 10.6.2 Key Events... 383 10.6.3 Drivers and Barriers... 384 10.7 United Kingdom... 386 10.7.1 Forecast... 386 10.7.2 Key Events... 392 15
10.7.3 Drivers and Barriers... 392 10.8 Japan... 395 10.8.1 Forecast... 395 10.8.2 Key Events... 400 10.8.3 Drivers and Barriers... 400 10.9 Australia... 403 10.9.1 Forecast... 403 10.9.2 Key Events... 408 10.9.3 10.9.3 Drivers and Barriers... 408 10.10 China... 410 10.10.1 Forecast... 410 10.10.2 Key Events... 415 10.10.3 Drivers and Barriers... 415 10.11 India... 417 10.11.1 Forecast... 417 10.11.2 Key Events... 422 10.11.3 Drivers and Barriers... 422 11 Appendix... 425 11.1 Bibliography... 425 11.2 Abbreviations... 451 11.3 Methodology... 458 11.4 Forecasting Methodology... 458 11.4.1 Diagnosed RA Patients... 458 11.4.2 Percentage of Drug-Treated Patients... 459 11.4.3 Drugs Included in Each Therapeutic Class... 459 11.4.4 Launch and Patent Expiry Dates... 460 11.4.5 General Pricing Assumptions... 461 16
11.4.6 Individual Drug Assumptions... 463 11.4.7 Generic and Biosimilar Erosion... 475 11.4.8 Pricing of Pipeline Agents... 475 11.5 Primary Research KOLs Interviewed for This Report... 478 11.6 Primary Research Prescriber Survey... 480 11.7 About the Authors... 480 11.7.1 Analyst... 480 11.7.2 Reviewer... 481 11.7.3 Therapy Area Director... 481 11.7.4 Epidemiologist... 482 11.7.5 Global Head of Healthcare... 483 11.8 About GlobalData... 484 11.9 Disclaimer... 484 1.1 List of Tables Table 1: Symptoms of RA... 35 Table 2: Risk Factors and Comorbidities for RA... 39 Table 3: 1987 ACR Diagnostic Criteria for RA... 43 Table 4: 10MM, Sources of RA Prevalence Data... 44 Table 5: 8MM, Total Prevalent Cases of RA, Ages 18 Years, Both Sexes, N, Selected Years 2013 2023... 56 Table 6: 8MM, Age-Specific Total Prevalent Cases of RA, Both Sexes, N (Row %), 2013... 58 Table 7: 8MM, Sex-Specific Total Prevalent Cases of RA, Ages 18 Years, N (Row %), 2013... 60 Table 8: 10MM, Diagnosed Prevalent Cases of RA, Ages 18 Years, Both Sexes, N, Selected Years 2013 2023... 62 Table 9: 1987 ACR Diagnostic Criteria for RA... 68 Table 10: 2010 ACR/EULAR Diagnostic Criteria for RA... 69 17
Table 11: Treatment Guidelines for RA Used by Each Country in the 10MM... 71 Table 12: ACR 2012 Criteria for RA Remission and Low/Moderate/High Disease Activity... 74 Table 13: EULAR 2013 Criteria for RA Remission... 75 Table 14: Most Prescribed Biologics for RA (After csdmards) in the Global Markets, 2014... 79 Table 15: RA Treatment Country Profile US... 87 Table 16: RA Treatment Country Profile France... 89 Table 17: RA Treatment Country Profile Germany... 91 Table 18: RA Treatment Country Profile Italy... 93 Table 19: RA Treatment Country Profile Spain... 95 Table 20: RA Treatment Country Profile UK... 98 Table 21: RA Treatment Country Profile Japan... 100 Table 22: RA Treatment Country Profile Australia... 103 Table 23: RA Treatment Country Profile China... 105 Table 24: RA Treatment Country Profile India... 107 Table 25: Leading Branded Treatments for RA 2014... 109 Table 26: Product Profile Enbrel... 111 Table 27: 10-Year, Open-Label Safety and Efficacy Trial of Enbrel: Efficacy Results at 11 Years for Completers... 112 Table 28: 10-year, Open-Label Safety and Efficacy Trial of Enbrel: Overall Safety Results... 113 Table 29: Enbrel SWOT Analysis, 2014... 114 Table 30: Global Sales Forecasts ($m) for Enbrel, 2013 2023... 115 Table 31: Product Profile Humira... 117 Table 32: Humira SWOT Analysis, 2014... 119 Table 33: Global Sales Forecasts ($m) for Humira, 2013 2023... 120 Table 34: Product Profile Remicade... 122 18
Table 35: Remicade SWOT Analysis, 2014... 125 Table 36: Global Sales Forecasts ($m) for Remicade, 2013 2023... 126 Table 37: Product Profile Simponi... 128 Table 38: Simponi SWOT Analysis, 2014... 130 Table 39: Global Sales Forecasts ($m) for Simponi, 2013 2023... 131 Table 40: Product Profile Cimzia... 133 Table 41: Cimzia SWOT Analysis, 2014... 135 Table 42: Global Sales Forecasts ($m) for Cimzia, 2013 2023... 136 Table 43: Product Profile Orencia... 138 Table 44: Orencia SWOT Analysis, 2014... 141 Table 45: Global Sales Forecasts ($m) for Orencia, 2013 2023... 142 Table 46: Product Profile Actemra... 146 Table 47: Actemra SWOT Analysis, 2014... 148 Table 48: Global Sales Forecasts ($m) for Actemra, 2013 2023... 149 Table 49: Product Profile Rituxan... 152 Table 50: Rituxan SWOT Analysis, 2014... 153 Table 51: Global Sales Forecasts ($m) for Rituxan, 2013 2023... 154 Table 52: Product Profile Inflectra/Remsima... 156 Table 53: Inflectra/Remsima SWOT Analysis, 2014... 157 Table 54: Product Profile Xeljanz... 161 Table 55: ORAL Standard ACR20 Responses for Tofacitinib vs. Humira and Placebo at Month 6... 162 Table 56: ORAL Step ACR20, 50, and 70 Responses for Xeljanz vs. Placebo at Month 6... 162 Table 57: Xeljanz SWOT Analysis, 2014... 164 Table 58: Global Sales Forecasts ($m) for Xeljanz, 2013 2023... 165 19
Table 59: Product Profile Iguratimod... 166 Table 60: Iguratimod SWOT Analysis, 2014... 167 Table 61: Global Sales Forecasts ($m) for Iguratimod, 2013 2023... 168 Table 62: Product Profile MTX... 170 Table 63: MTX SWOT Analysis, 2014... 171 Table 64: Global Sales Forecasts ($m) for MTX, 2013 2023... 172 Table 65: Biosimilars Pipeline for RA, 2013... 176 Table 66: Physician Uptake of Biosimilar Products for RA Across the 10MM, 2014... 183 Table 67: Global Sales Forecasts ($m) for Etanercept Biosimilars, 2013 2023... 183 Table 68: Global Sales Forecasts ($m) for Adalimumab Biosimilars, 2013 2023... 184 Table 69: Global Sales Forecasts ($m) for Infliximab Biosimilars, 2013 2023... 186 Table 70: Global Sales Forecasts ($m) for Certolizumab Pegol Biosimilars, 2013 2023... 187 Table 71: Global Sales Forecasts ($m) for Abatacept Biosimilars, 2013 2023... 188 Table 72: Global Sales Forecasts ($m) for Tocilizumab Biosimilars, 2013 2023... 189 Table 73: Global Sales Forecasts ($m) for Rituximab Biosimilars, 2013 2023... 190 Table 74: Summary of Minor Therapeutic Drug Classes Used to Treat RA, 2014... 192 Table 75: Unmet Need and Opportunity in RA, 2014... 194 Table 76: Comparison of Therapeutic Drug Classes in Development for RA, 2014... 214 Table 77: Product Profile Sarilumab... 216 Table 78: MOBILITY Study Part, A, Results for Sarilumab at Week 12... 217 Table 79: MOBILITY Study, Part B, Results for Sarilumab at Week 52... 217 Table 80: Sarilumab SWOT Analysis, 2014... 221 Table 81: Global Sales Forecasts ($m) for Sarilumab, 2013 2023... 222 Table 82: Product Profile Sirukumab... 223 20
Table 83: Sirukumab SWOT Analysis, 2014... 227 Table 84: Global Sales Forecasts ($m) for Sirukumab, 2013 2023... 228 Table 85: Product Profile Clazakizumab... 230 Table 86: Phase IIb Study of Clazakizumab: ACR Responses After 12 Weeks... 231 Table 87: Phase IIb Study of Clazakizumab: ACR Responses After 24 Weeks... 231 Table 88: Clazakizumab SWOT Analysis, 2014... 234 Table 89: Global Sales Forecasts ($m) for Clazakizumab, 2013 2023... 235 Table 90: Product Profile Cosentyx... 237 Table 91: Cosentyx SWOT Analysis, 2014... 240 Table 92: Global Sales Forecasts ($m) for Cosentyx, 2013 2023... 241 Table 93: Product Profile Tregalizumab... 243 Table 94: Tregalizumab SWOT Analysis, 2014... 246 Table 95: Global Sales Forecasts ($m) for Tregalizumab, 2013 2023... 246 Table 96: Product Profile Mavrilimumab... 248 Table 97: Mavrilimumab SWOT Analysis, 2014... 251 Table 98: Global Sales Forecasts ($m) for Mavrilimumab, 2013 2023... 252 Table 99: Product Profile Denosumab... 254 Table 100: Denosumab SWOT Analysis, 2014... 257 Table 101: Global Sales Forecasts ($m) for denosumab in RA, 2013 2023... 258 Table 102: Product Profile Baricitinib... 260 Table 103: Baricitinib Phase IIb Trial, Part A: ACR Responses at Week 12... 261 Table 104: Baricitinib Phase IIb Trial, Part B: ACR Responses at Weeks 24 and 52... 261 Table 105: Baricitinib Phase IIb Trial, Part A: Safety at Week 12... 263 Table 106: Baricitinib Phase IIb Trial, Part A, Laboratory Values at Week 12... 263 21
Table 107: Baricitinib SWOT Analysis, 2014... 266 Table 108: Global Sales Forecasts ($m) for Baricitinib, 2013 2023... 267 Table 109: Product Profile Peficitinib... 269 Table 110: Peficitinib SWOT Analysis, 2014... 273 Table 111: Global Sales Forecasts ($m) for Peficitinib, 2013 2023... 274 Table 112: Product Profile Decernotinib... 275 Table 113: Phase IIb tudy of Decernotinib: ACR Responses at Week 24... 276 Table 114: Decernotinib SWOT Analysis, 2014... 279 Table 115: Global Sales Forecasts ($m) for Decernotinib, 2013 2023... 280 Table 116: Product Profile Filgotinib... 281 Table 117: Filgotinib SWOT Analysis, 2014... 285 Table 118: Global Sales Forecasts ($m) for Filgotinib, 2013 2023... 286 Table 119: Product Profile Masitinib... 288 Table 120: ACR Response to Masitinib in RA (12 Weeks)... 289 Table 121: ACR Responses for Masitinib in the Phase IIa ITT Population (12 82 Weeks)... 289 Table 122: Masitinib SWOT Analysis, 2014... 292 Table 123: Global Sales Forecasts ($m) for Masitinib, 2013 2023... 293 Table 124: Product Profile RAVAX... 294 Table 125: RAVAX SWOT Analysis, 2014... 297 Table 126: Drugs in Phase II of Development for RA, 2014... 299 Table 127: Key Companies in the RA Market, 2014... 303 Table 128: AbbVie s RA Portfolio Assessment, 2014... 306 Table 129: Pfizers s RA Portfolio Assessment, 2014... 309 Table 130: Amgen s RA Portfolio Assessment, 2014... 312 22
Table 131: J&J s RA Portfolio Assessment, 2014... 314 Table 132: Eli Lilly s RA Portfolio Assessment, 2014... 316 Table 133: BMS RA Portfolio Assessment, 2014... 318 Table 134: UCB s RA Portfolio Assessment, 2014... 319 Table 135: Roche s RA Portfolio Assessment, 2014... 321 Table 136: GSK s RA Portfolio Assessment, 2014... 323 Table 137: Novartis RA Portfolio Assessment, 2014... 325 Table 138: Sanofi s RA Portfolio Assessment, 2014... 327 Table 139: AstraZeneca -MedImmune s RA Portfolio Assessment, 2014... 329 Table 140: Astellas s RA Portfolio Assessment, 2014... 331 Table 141: Vertex s RA Portfolio Assessment, 2014... 333 Table 142: Daiichi Sankyo s RA Portfolio Assessment, 2014... 335 Table 143: Global Sales Forecasts ($m) for RA, 2013 2023... 339 Table 144: Global RA Market Drivers and Barriers, 2013 2023... 342 Table 145: Sales Forecasts ($m) for RA in the United States, 2013 2023... 347 Table 146: Key Events Impacting Sales for RA in the US, 2013 2023... 350 Table 147: RA Market in the US Drivers and Barriers, 2013 2023... 351 Table 148: Sales Forecasts ($m) for RA in France, 2013 2023... 355 Table 149: Key Events Impacting Sales for RA in France, 2013 2023... 358 Table 150: RA Market in France Drivers and Barriers, 2013 2023... 358 Table 151: Sales Forecasts ($m) for RA in Germany, 2013 2023... 363 Table 152: Key Events Impacting Sales for RA in Germany, 2013 2023... 366 Table 153: RA Market in Germany Drivers and Barriers, 2013 2023... 367 Table 154: Sales Forecasts ($m) for RA in Italy, 2013 2023... 372 23
Table 155: Key Events Impacting Sales for RA in Italy, 2013 2023... 375 Table 156: RA Market in Italy Drivers and Barriers, 2013 2023... 375 Table 157: Sales Forecasts ($m) for RA in Spain, 2013 2023... 380 Table 158: Key Events Impacting Sales for RA in Spain, 2013 2023... 383 Table 159: RA Market in Spain Drivers and Barriers, 2013 2023... 384 Table 160: Sales Forecasts ($m) for RA in the UK, 2013 2023... 389 Table 161: Key Events Impacting Sales for RA in the UK, 2013 2023... 392 Table 162: RA Market in the UK Drivers and Barriers, 2013 2023... 392 Table 163: Sales Forecasts ($m) for RA in Japan, 2013 2023... 397 Table 164: Key Events Impacting Sales for RA in Japan, 2013 2023... 400 Table 165: RA Market in Japan Drivers and Barriers, 2013 2023... 400 Table 166: Sales Forecasts ($m) for RA in Australia, 2013 2023... 405 Table 167: Key Events Impacting Sales for RA in Australia, 2013 2023... 408 Table 168: RA Market in Australia Drivers and Barriers, 2013 2023... 408 Table 169: Sales Forecasts ($) for RA in China, 2013 2023... 412 Table 170: Key Events Impacting Sales for RA in China, 2013 2023... 415 Table 171: RA Market in China Drivers and Barriers, 2013 2023... 415 Table 172: Sales Forecasts ($m) for RA in India, 2013 2023... 419 Table 173: Key Events Impacting Sales for RA in India, 2013 2023... 422 Table 174: RA Market in India Drivers and Barriers, 2013 2023... 422 Table 175: Key Launch Dates of RA Products in the 10MM... 460 Table 176: Key Patent Expiries... 461 Table 177: High-Prescribing Physicians (non-kols) Surveyed, By Country... 480 24
1.2 List of Figures Figure 1: Normal Synovial Joint and Synovial Joint with RA... 31 Figure 2: Cellular and Cytokine Targets for the Current RA Drugs... 34 Figure 3: 8MM, Total Prevalent Cases of RA, Ages 18 Years, Both Sexes, N, 2013 2023... 57 Figure 4: 8MM, Age-Specific Total Prevalent Cases of RA, Both Sexes, N, 2013... 59 Figure 5: 8MM, Sex-Specific Total Prevalent Cases of RA, Ages 18 Years, N, 2013... 61 Figure 6: 10MM, Diagnosed Prevalent Cases of RA, Ages 18 Years, Both Sexes, N, 2013 2023... 63 Figure 7: 10MM, Age-Standardized Prevalence of RA (%), Ages 18 Years, 2013... 64 Figure 8: Disease Management Flowchart for Early RA ACR 2012... 75 Figure 9: Disease Management Flowchart for Established RA ACR 2012... 76 Figure 10: Flowchart for the Management of RA EULAR 2013... 77 Figure 11: Biosimilar Prescribing Habits in RA Across the 10MM, 2014... 182 Figure 12: Global Sales Forecasts ($m) for Enbrel vs. Etanercept Biosimilars, 2013 2023... 184 Figure 13: Global Sales Forecasts ($m) for Humira vs. Adalimumab Biosimilars, 2013 2023... 185 Figure 14: Global Sales Forecasts ($m) for Remicade vs. Infliximab Biosimilars, 2013 2023... 187 Figure 15: Global Sales Forecasts ($m) for Cimzia vs. Certolizumab Pegol Biosimilars, 2013 2023... 188 Figure 16: Global Sales of Orencia vs. Abatacept (IV) Biosimilars, 2013 2023... 189 Figure 17: Global Sales of Actemra vs. Tocilizumab (IV) Biosimilars, 2013 2023... 190 Figure 18: Global Sales of Rituxan vs. Rituximab Biosimilars, 2013 2023... 191 Figure 19: RA Clinical Trials By Drug Class, 2014... 207 Figure 20: RA Phase II III Pipeline, 2014... 209 Figure 21: Competitive Assessment of Late-Stage Pipeline Agents in RA, 2013 2023... 213 Figure 22: Clinical and Commercial Positioning of Sarilumab... 220 Figure 23: Clinical and Commercial Positioning of Sirukumab... 227 25
Figure 24: Clinical and Commercial Positioning of Clazakizumab... 234 Figure 25: Clinical and Commercial Positioning of Cosentyx... 239 Figure 26: Clinical and Commercial Positioning of Tregalizumab... 245 Figure 27: Clinical and Commercial Positioning of Mavrilimumab... 251 Figure 28: Clinical and Commercial Positioning of denosumab in RA... 257 Figure 29: Clinical and Commercial Positioning of Baricitinib... 266 Figure 30: Clinical and Commercial Positioning of Peficitinib... 272 Figure 31: Clinical and Commercial Positioning of Decernotinib... 278 Figure 32: Clinical and Commercial Positioning of Filgotinib... 284 Figure 33: Clinical and Commercial Positioning of Masitinib... 291 Figure 34: Clinical and Commercial Positioning of RAVAX... 297 Figure 35: Company Portfolio Gap Analysis in RA, 2013 2023... 304 Figure 36: AbbVie SWOT Analysis in RA, 2013 2023... 307 Figure 37: Pfizer SWOT Analysis in RA, 2013 2023... 310 Figure 38: Amgen SWOT Analysis in RA, 2013 2023... 312 Figure 39: J&J SWOT Analysis in RA, 2013 2023... 315 Figure 40: Eli Lilly SWOT Analysis in RA, 2013 2023... 317 Figure 41: BMS SWOT Analysis in RA, 2013 2023... 318 Figure 42: UCB SWOT Analysis in RA, 2013 2023... 320 Figure 43: Roche SWOT Analysis in RA, 2013 2023... 322 Figure 44: GSK SWOT Analysis in RA, 2013 2023... 324 Figure 45: Novartis SWOT Analysis in RA, 2013 2023... 326 Figure 46: Sanofi SWOT Analysis in RA, 2013 2023... 328 Figure 47: AstraZeneca/MedImmune SWOT Analysis in RA, 2013 2023... 330 26
Figure 48: Astellas SWOT Analysis in RA, 2013 2023... 332 Figure 49: Vertex SWOT Analysis in RA, 2013 2023... 334 Figure 50: Daiichi Sankyo SWOT Analysis in RA, 2013 2023... 336 Figure 51: Global Sales for RA by Region, 2013 2023... 341 Figure 52: Sales for RA in the United States by Drug Class, 2013 2023... 349 Figure 53: Sales for RA in France by Drug Class, 2013 2023... 357 Figure 54: Sales for RA in Germany by Drug Class, 2013 2023... 365 Figure 55: Sales for RA in Italy by Drug Class, 2013 2023... 374 Figure 56: Sales for RA in Spain by Drug Class, 2013 2023... 382 Figure 57: Sales for RA in the UK by Drug Class, 2013 2023... 391 Figure 58: Sales for RA in Japan by Drug Class, 2013 2023... 399 Figure 59: Sales for RA in Australia by Drug Class, 2013 2023... 407 Figure 60: Sales for RA in China by Drug Class, 2013 2023... 414 Figure 61: Sales for RA in India by Drug Class, 2013 2023... 421 27
Introduction 2 Introduction 2.1 Catalyst The Rheumatoid Arthritis (RA) market will grow over the 2013 2023 forecast period, driven by a number of new product launches, such as: Novel biologics Anti-interleukin (IL)-6 biologics Small molecules, including janus kinase (JAK) inhibitors Other factors that will drive market expansion are growth in the emerging markets of China, India, and Australia, where product launches extend product lifecycles. In addition, there will be an increase in the prevalence of RA across the 10 major markets (10MM) covered in this report. The loss of patent protection for the anti-tumor necrosis factor (TNF) marketed brands will allow for the emergence of biosimilars, such as Celltrion s Remsima (infliximab)/hospira s Inflectra (infliximab), which is a Remicade biosimilar. The patent expiries begin in 2015 and 2016, respectively, for the current market leaders: J&J s Remicade AbbVie s Humira The catalysts and objectives for this report are to: Determine the impact that biosimilars will have on the RA market Assess the uptake of JAK inhibitors, including Pfizer s Xeljanz (tofacitinib) and other pipeline agents Identify the unmet needs in the RA market Determine the remaining opportunities in the RA market 28
Introduction 2.2 Related Reports GlobalData (2014). PharmaPoint: Ulcerative Colitis Global Drug Forecast and Market Analysis to 2022, Event-Driven Update, September 2014, GDHC005EPIDR GlobalData (2014). PharmaPoint: Crohn's Disease Global Drug Forecast and Market Analysis to 2022, January 2014, GDHC77PIDR GlobalData (2014). PharmaPoint: Atopic Dermatitis Global Drug Forecast and Market Analysis to 2022, November 2013, GDHC66PIDR GlobalData (2014). PharmaPoint: Systemic Lupus Erythematosus and Lupus Nephritis Global Drug Forecast and Market Analysis to 2022, October 2013, GDHC65PIDR GlobalData (2014). PharmaPoint: Psoriasis Global Drug Forecast and Market Analysis to 2022, May 2013, GDHC48PIDR 2.3 Upcoming Related Reports GlobalData (2015). Opportunity Analyzer: Ankylosing Spondylitis and Non-Radiographic Axial Spondyloarthritis Global Drug Forecast and Market Analysis to 2023, to be published in March 2015 GlobalData (2015). PharmaPoint: Atopic Dermatitis Global Drug Forecast and Market Analysis to 2022, Event-Driven Update, to be published in January 2015 GlobalData (2015). PharmaPoint: Systemic Lupus Erythematosus and Lupus Nephritis Global Drug Forecast and Market Analysis to 2022, Event-Driven Update, to be published in January 2015 29
Appendix 11.8 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, San Francisco, Boston, London, India, Korea, Japan, Singapore, and Australia. 11.9 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. 484