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REF ER EN CE CO DE GDH C021POA | PUBLICAT ION D AT E AU GU ST 2014 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Executive Summary Table above presents the key metrics for graft- Key Metrics for Graft-Versus-Host Disease (GVHD) in the Six Major Pharmaceutical Markets, 2013– 2018 versus-host disease (GVHD) in the six major pharmaceutical markets (US, France, Germany, 2013 Epidemiology First allogeneic HSCTs (men and women) (N) 6MM 15,991 Diagnosed incident cases of aGVHD in first allogeneic HSCTs (men and women) (N), 6MM 8,062 Diagnosed incident cases of cGVHD in first allogeneic HSCTs (men and women) (N), 6MM 7,359 Italy, Spain, and UK) covered in this report during the forecast period from 2013–2018. Steady Growth Expected in the US and EU 2013 Market Sales GVHD Markets from 2013–2018 The GVHD market was valued at $297.0m across US $209.7m 5EU $86.0m the 6MM in 2013, and is expected to increase to $295.7m $409.0m in 2018, at a Compound Annual Growth Total Pipeline Assessment Rate (CAGR) of 6.61%. Growth is anticipated to be Number of drugs in Phase I–II 33 Number of first-in-class drugs in Phase I–IIb 26 Key Events (2013–2018) Level of Impact 2014 Food and Drug Administration (FDA) approval and restricted* launch of Prochymal (remestemcel-L) for aGVHD ↑↑ 2015 European Medicines Agency (EMA) approval and restricted* launch of Prochymal for aGVHD ↑↑ 2016 ATG-Fresenius (EZ-2053) launch ↑↑ 2016 Budenofalk (budesonide) EU launch slowest in the US, as there are fewer market changes expected during the five-year forecast period. In contrast, due to the multiple product launches in Europe, growth in the 5EU is expected to accelerate towards the end of the forecast period, posting a CAGR of 9.42% during this timeframe. In addition, multiple biologic products ↑ 2018 Launch of Leukotac (inolimomab) ↑↑↑ 2018 Launch of Begedina (anti-CD26) ↑↑↑ will fall off their respective patent cliffs during the 2013–2018 forecast period. However, this will not impact the present GVHD forecast for two very important reasons: First, biosimilar versions of key 2018 Market Sales US $273.0m 5EU $134.0m Total $407.0m Source: GlobalData off-label GVHD (rituximab) biologics, such as Rituxan and Campath/Lemtrada (alemtuzumab), are in a very early developmental For the purposes of this report, the six major pharmaceutical markets = US and 5EU (France, Germany, Italy, Spain, and UK). stage and to date have failed clinical trials. aGVHD = acute GVHD; cGVHD = chronic GVHD; HSTC = hematopoietic stem cell transplantation Secondly, hematologists across the 6MM are not expected to use biosimilar versions of branded biologics in GVHD patients whose health is already severely compromised. Furthermore, key opinion leaders (KOLs) interviewed by GlobalData unanimously agreed that they would prefer for new Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 2 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Executive Summary biosimilars to be tested in a GVHD clinical trial setting before they use them in the clinic. data on off-label second-line therapies in both aGVHD and cGVHD, which will lead to In total, six products are expected to enter the increased market by 2018. Osiris Therapeutics/Mesoblast’s Bristol-Myers 2015 (5EU), reaching $12.2m in sales from the known as ATG-F) is expected to enter the US already-established Squibb’s (BMS’) Orencia Increasing numbers of HSCT patients. A trend towards prescribing of biologics and patented small molecules, which will increase GVHD market, and these two products are the GVHD market value. estimated to generate 2018 sales of $11.9m and $4.5m, respectively. Both Jazz Pharmaceuticals’ of (abatacept). 6MM in 2018. Dr. Falk Pharma’s Budenofalk is 2017, while in the same year, ATG-Fresenius (also uptake treatments, such as Roche’s Rituxan and Prochymal is expected to launch in 2014 (US) and forecast to enter the European GVHD market in Academic publication of more favorable clinical A high incidence of cGVHD throughout the Leukotac and Adienne Pharma’s Begedina are 2013–2018 forecast period, which will lead to forecast to enter the GVHD market in 2018, with an Leukotac being launched only in the 5EU. Due to prescriptions. their anticipated premium pricing, Begedina and increase in expensive long-term The release of company-funded randomized Leukotac are expected to add over $18m to the clinical trial data, which can be leveraged by 6MM sales in 2018. reimbursement agencies to fund expensive Major drivers of growth in the GVHD market over biologics and patented small molecules. the forecast period include: T-regulatory (T-reg) cell and selective T-cell (T- The launch of new therapies with orphan lymphocyte) therapies currently developed in designations. Since orphan drugs are entitled academic institutes, which could be licensed to premium pricing, the aGVHD market will by pharmaceutical companies and drive their accrue increased revenue. clinical development. Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 3 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Executive Summary Major barriers to the growth of the GVHD market during the forecast period include: in most EU countries could hinder future drug uptake. Reimbursement pressures in the EU could lead to the funding of generic small molecules The conservative approach to GVHD treatment The complex pathophysiology of the disease or low-efficacy drugs because the latter are and the lack of adequate GVHD animal models already in stock. For example, Johnson & create Johnson’s (J&J’s) Remicade (infliximab) is development. favored in the UK at the expense of Amgen’s Enbrel (adalimumab), purely because the former drug is what can be funded by the National Health Service (NHS) at the moment, significant challenges during drug Figure below illustrates the global GVHD sales for the six major markets (6MM) (US and 5EU) for all three GVHD indications during the five-year forecast period from 2013–2018. as it is readily available. The lack of national treatment guidelines in all 6MM could lead to a significant proportion of patients being enrolled in clinical trials, thus dissolving potential future GVHD revenues. Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 4 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Executive Summary Global Sales for GVHD by Region and GVHD Indication, 2013–2018 2013 - Total GVHD sales $295.7m 3% 5% 5% 26% 10% 39% 6% 71% 35% 2018 - Total GVHD sales $407.0m 5% 3% 5% 36% 30% 11% 9% 67% 34% US France Germany Italy Spain UK aGVHD cGVHD Prophylaxis Source: GlobalData Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 5 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Executive Summary Research and Development Strategies will pipeline Drastically Shape the GVHD Pipeline Over the prophylaxis. Next Five Years In addition to the above strategies, blocking Over the past two decades, the GVHD market has communication between host antigen-presenting been evolving, with the introduction of biological cells and donor T cells has been a focus of R&D in and patented small-molecule immunosuppressive GVHD for over two decades. However, most of off-label therapies being added to the treatment these R&D ventures involve academically-run paradigm. The current research and development clinical studies. Targeting niche subgroups within (R&D) programs in GVHD are exciting, with novel GVHD, such as steroid-refractory aGVHD and therapies (such as Adienne Pharma’s Begedina) cGVHD, also emerges as one of the key R&D and potential first-in-class treatments (such as strategies in the GVHD pipeline, with 31 pipeline mesenchymal products targeting these populations. stem cell [MSC] therapies). targeting the indication of GVHD However, as a consequence of low funds accrual Unmet Needs Remain Largely Unattained in (as seen in clinical trial NCT00623012), low patient GVHD Management recruitment (as seen in clinical trial NCT00616954), and clinical trial failures (as seen in clinical trial NCT00720850), the GVHD pipeline has faced a period of slow development. Currently, R&D strategies in GVHD are characterized by a trend towards improving prophylactic regimens, inhibiting T-cell proliferation and activation, using treatments adopted from hematologic indications, and targeting niche subgroups within the GVHD population. GVHD is a market with a substantial number of unattained unmet needs. This is compounded by the fact that there are no guidelines in place for the management of GVHD; instead, there are only recommendations for several therapies. This is largely due to the orphan nature of the disease, but it is mainly because of the lack of randomized clinical trials and the use of variable clinical trial endpoints in the studies that have been conducted to date. This has resulted in clinical data that are The current GVHD prophylactic regimens are not comparable and/or not directly applicable to all tailored to the type of conditioning and transplant groups of GVHD patients, which, in turn, means type used for HSCT. However, these therapies that guidelines cannot be devised. carry a risk of opportunistic infection and provide inadequate GVHD prophylaxis. As a result, the R&D focus in GVHD remains partly fixated on prophylaxis. There are three products in the Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 6 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Executive Summary Another crucial unmet need is the lack of GVHD- In all, despite the ongoing development of products specific therapies that induce durable remission. and/or initiatives for the resolution of each unmet Although the treatments that are currently used in need, the GVHD market is a difficult one to the management of GVHD (both acute and introduce rapid changes into, as any changes chronic) are established and have a good could affect the survival outcomes for patients. As reputation regarding their efficacy profiles for their such, the highest priority is for more randomized respective indication, they do not seem to offer clinical trials to be conducted. durable remission in the GVHD setting. One example is the extracorporeal photophoresis (ECP) The GVHD Market Provides an Abundance of Opportunities system, which does not have toxicities and can induce a quick response, but this response is longlasting in only 20–30% of patients. Also, therapies with minimal side effects are desired, since GVHD patients are generally not physically fit and cannot endure additional physical stress due to conditioning or prophylaxis drugs, or other drugs, such as antibiotics, antivirals, and antifungal therapies, that are used to treat or prevent the There is a large opportunity for pharmaceutical companies to conduct randomized clinical trials on immunosuppressive therapies that are being used off-label in the GVHD setting. This opportunity could be exploited by supporting existing academic organizations in their efforts to clarify the treatment algorithm for GVHD in order to offer optimized treatment outcomes for patients receiving HSCT. Further incorporation of specific primary endpoints other conditions that they develop. in the clinical trial setting of aGVHD and cGVHD Focusing on patient segments, the management of steroid-refractory aGVHD (SR-aGVHD) patients and GVHD patients with respiratory involvement is challenging and becomes increasingly difficult with increasing disease duration. can be circumvented prophylactic measures, which with could better possibly minimize the manifestation of GVHD. However, the complex pathophysiology of GVHD, combined with the challenge of personalized treatment design in GVHD, renders a perfect prophylaxis unattainable for the foreseeable future. pharmaceutical industry. Implementing a more robust set of endpoints will allow drug developers to generate accurate and comparable data that physicians can rely upon in order to adjust their To some extent, most of the aforementioned unmet needs remains an opportunity for both academia and the GVHD management protocols. Although targeted and stratified clinical trials would likely lead to drugs being approved for narrower indications within the GVHD market, the upside is that the medical community could come closer to a much needed therapy for sclerotic cGVHD patients. Overall, there is a great need for therapies with better safety and efficacy profiles Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 7 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Executive Summary that are specific to GVHD pathophysiology and Figure below provides GlobalData’s competitive account for the nature of the disease. Still, there is assessment of the GVHD prophylaxis landscape room in the market for products for sclerotic from 2013–2018. cGVHD patients, particularly given the acute and poor prognosis elements of GVHD. Competitive Assessment of GVHD Prophylaxis OffLabel Therapies and Late-Stage Pipeline Agents, 2013–2018 Rituxan Remains the Protagonist of the GVHD 4.5 Market Standard of care: CsA+MTX ATG-Fresenius based prophylaxis Prograf and Rapamune instead of CsA and as such, the historic use of calcineurin inhibitors with a short course of methotrexate (MTX) will remain prophylactic regimen the most through avidly-used 2018. Astellas Pharma’s Prograf (tacrolimus) and anti-thymocyte globulins (ATGs) are expected to also remain key products for prophylaxis. They have been widely COMMERCIAL SCORE 4.0 The prophylaxis setting of GVHD is conservative, Rapamune+CsA without MTX Rituxan based prophylaxis Velcade based prophylaxis 3.5 Lemtrada based prophylaxis Thymoglobuline based prophylaxis 3.0 Orencia based prophylaxis 2.5 MultiStem based prophylaxis 2.0 2.0 2.5 3.0 3.5 CLINICAL SCORE 4.0 4.5 5.0 Source: GlobalData CsA = cyclosporine A MTX = methotrexate used to date and are trusted by hematologists. In GlobalData’s the SR-aGVHD prevails as the most urgent and poorly prophylaxis landscape, Roche’s Rituxan emerged managed population in the aGVHD setting, and as as the most clinically and commercially attractive such, there are plenty of innovative initiatives prophylaxis regimen (see figure below). It is a targeting this group. Because of the complexity of favored therapy that is used in both aGVHD and aGVHD cGVHD prophylaxis due to its growing reputation in immunotherapies and immunosuppressive small the Sanofi/Genzyme’s molecules have and are being used for its Campath/Lemtrada will remain an essential part of management, giving way to a complex landscape conditioning regimens, but not prophylaxis, due to where establishing reputation among hematology its highly infectious and generally harmful side communities through trial funding and proven effects. Over the 2013–2018 forecast period, efficacy is key for an aGVHD therapy to move increasing adverse reactions to classic therapy forward. field. competitive assessment Meanwhile, of pathophysiology, many different might give rise to Orencia-based prophylaxis, as well as MultiStem (modified mesenchymal stem cells)-based prophylaxis, which promises effective prophylaxis with only one use. Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 8 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Executive Summary Figure below provides GlobalData’s competitive assessment of the aGVHD landscape from 2013– Competitive Assessment of cGVHD Off-Label Therapies and Late-Stage Pipeline Agents, 2013– 2018 2018. 5.0 Nipent Gleevec Rituxan 4.5 5.0 Nipent Leukotac COMMERCIAL SCORE mTOR inhibitors Rituxan 4.5 COMMERCIAL SCORE Competitive Assessment of aGVHD Off-Label Therapies and Late-Stage Pipeline Agents, 2013– 2018 MMF ECP 4.0 CD25α inhibitor therapies TNFα inhibitor therapies 3.0 mTOR inhibitor CD25α inhibitor therapies Lemtrada 2.5 2.5 3.0 3.5 CLINICAL SCORE 4.0 4.5 5.0 ECP = extracorporeal photophoresis; MMF = mycophenolate mofetil; mTOR = mammalian target of rapamycin Prochymal Begedina 3.5 Source: GlobalData Lemtrada 2.5 Standard of care: Steroids 2.0 Thymoglobuline 3.0 ECP 4.0 2.0 Standard of care: CsA + Steroids 3.5 MMF 2.0 2.0 2.5 3.0 3.5 4.0 CLINICAL SCORE 4.5 5.0 Source: GlobalData X = Clinical Score; Y = Commercial Score CsA = cyclosporine A; ECP = extracorporeal photophoresis; mTOR = mammalian target of rapamycin; TNFα = tumor necrosis factor alpha What Do Physicians Think? In regard to which part of GVHD management requires The cGVHD market remains stagnant from the improvement, KOLs interviewed by GlobalData offered the following: innovation point of view. Initial therapy with “I think the way to move forward [in the steroids is the mainstay of treatment for cGVHD, management of GVHD], clearly, is prophylaxis. but because of the nature of steroid therapy — That’s the way it is going to get better [in terms of specifically, the severe side effects associated with improved outcomes in HSCT].” its long-term use — it cannot be used chronically. [US] KOL, March 2014 Therefore, other treatments such as ECP, Rituxan, Nipent (pentostatin), and Gleevec (imatinib mesylate), are expected to face unhindered future growth in the cGVHD setting during the 2013 to 2018 forecast period, and will emerge as the most clinically and commercially attractive therapies in GlobalData’s competitive assessment of cGVHD landscape, as shown in figure below. the “...actually, the major point in this [GVHD management] is that when you start tapering immunosuppressant therapy when you are already using low doses of prednisone and [a] calcineurin inhibitor, there is a time point where a subset of these patients flare again with chronic GVHD. There is no standard tapering protocol.” [EU] KOL, March 2014 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 9 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Executive Summary Commenting on the management of patients with Discussing the efficacy of the late-stage pipeline toxicities, a KOL said: therapy, Therakos’ Uvadex (methoxsalen), an ECP “I would say that for MSC therapies, ECP, and therapy, a KOL said: rituximab, I feel quite comfortable regarding [the] “It’s a very safe treatment if we compare [it] to all management of their toxicity, and then the rest of older therapies, because with ECP you have an drugs, actually, are hard to manage, and you have immunosuppressive effect, but it’s a progressive a quite high incidence of infections, which is not and chronic immunosuppressive effect, not a easy when you have a patient with pre-existing or drastic one….Probably, it’s important to introduce serious toxicities. You can’t help these patients; very early this kind of treatment, and to not to they usually succumb to organ failure.” prolong [it] if there is no effect. So, it’s important to [EU] KOL, March 2014 do either eight or 10 photophoresis cycles to know if there is a response or not, and after, to switch to Discussing therapy, the safety Osiris of late-stage pipeline Therapeutics/Mesoblast’s another therapy. But probably, photophoresis has an important place in the therapeutic setting in Prochymal, a KOL said: acute and in chronic [GVHD]. In chronic [GVHD], “I mean, there are [a] number of potential safety it’s definitely effective in cutaneous and ocular issues about what their [MSC therapies’] impact is. involvement, as well as in mucositis.” I expect Prochymal will receive a black box [EU] KOL, March 2014 warning regarding viral infection or tumor relapse risk or issues with chimers. The honest truth is, if you are applying them in a setting of prophylaxis, Commenting on the efficacy of Roche’s Rituxan, a KOL stated: that is the most comfortable way — and there are “I have a good experience with rituximab; that is data out there to support mesenchymal stem cell very effective for cutaneous involvement and in therapy in prophylaxis — then the downsides of sclerosis, having GVHD probably outweigh any potential expression[s] of chronic [GVHD] disease. It [also] perceived risk of the product. If the product has good results in ocular lesions and mucositis.” which are worked, I wouldn’t be concerned about the the most frequent [EU] KOL, March 2014 potential risks of it, because having a product that worked in that setting would outweigh any potential risk, but I don’t think the product worked.” [EU] KOL, March 2014 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 10 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Executive Summary Discussing the challenges associated with the available treatment options in the GVHD market, a KOL said: “The fact that there is such [a] big array of immunosuppressive drugs [used off-label to treat GVHD], it makes it difficult to decide [what treatment to select, especially as] none of them have been studied properly [within the GVHD setting].” [US] KOL, April 2014 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 11 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Table of Contents 1 1 2 3 Table of Contents Table of Contents ..................................................................................................................... 12 1.1 List of Tables .................................................................................................................... 19 1.2 List of Figures ................................................................................................................... 23 Introduction ............................................................................................................................... 24 2.1 Catalyst............................................................................................................................. 24 2.2 Related Reports ................................................................................................................ 25 2.3 Upcoming Related Reports ............................................................................................... 25 Disease Overview ..................................................................................................................... 26 3.1 3.1.1 Etiology ......................................................................................................................... 26 3.1.2 Pathophysiology ............................................................................................................ 28 3.1.3 Classification and Prognosis ......................................................................................... 29 3.2 4 Etiology and Pathophysiology ........................................................................................... 26 Symptoms ......................................................................................................................... 31 Epidemiology ............................................................................................................................ 33 4.1 Disease Background ......................................................................................................... 33 4.2 Risk Factors and Comorbidities ........................................................................................ 34 4.3 Global Trends ................................................................................................................... 36 4.4 Forecast Methodology....................................................................................................... 37 4.4.1 Sources Used................................................................................................................ 39 4.4.2 Sources Not Used ......................................................................................................... 45 4.4.3 Diagnosed Incident Cases of HSCTs ............................................................................ 46 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 12 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Table of Contents 4.4.4 Diagnosed Incident Cases of Autologous HSCTs .......................................................... 48 4.4.5 Diagnosed Incident Cases of Allogeneic HSCTs ........................................................... 49 4.4.6 Diagnosed Incident Cases of aGVHD ........................................................................... 50 4.4.7 Four-Year Diagnosed Prevalent Cases of aGVHD ........................................................ 50 4.4.8 Diagnosed Incident Cases of cGVHD............................................................................ 51 4.4.9 Five-Year Diagnosed Prevalent Cases of cGVHD ......................................................... 51 4.5 4.5.1 Diagnosed Incident Cases of HSCTs ............................................................................ 52 4.5.2 Diagnosed Incident Cases of Autologous HSCTs .......................................................... 54 4.5.3 Diagnosed Incident Cases of Allogeneic HSCTs ........................................................... 55 4.5.4 Diagnosed Incident Cases of aGVHD ........................................................................... 57 4.5.5 Four-Year Diagnosed Prevalent Cases of aGVHD ........................................................ 59 4.5.6 Diagnosed Incident Cases of cGVHD ............................................................................ 61 4.5.7 Five-Year Diagnosed Prevalent Cases of cGVHD ......................................................... 62 4.6 5 Epidemiological Forecast for GVHD (2013–2023) ............................................................. 52 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 Current Treatment Options ....................................................................................................... 67 5.1 Overview ........................................................................................................................... 67 5.2 Product Profiles – Major Therapies ................................................................................... 69 5.2.1 Methylprednisolone (numerous brand and generic names) ........................................... 69 5.2.2 Cyclosporine (numerous brands and generic names).................................................... 73 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 13 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Table of Contents 5.2.3 5.3 5.3.1 Anti-Thymocyte Globulin (ATG) Therapies .................................................................... 78 Product Profiles – Off-Label Therapies.............................................................................. 83 Biologics (Tumor Necrosis Factor (TNF)α Inhibitors, Interleukin-2 Receptor α (CD25) Inhibitors, Co-Stimulatory Blockers and Other Biologics) .............................................. 83 5.3.2 Small Immunosuppressive Molecules (mTOR Inhibitors, Solid Organ Transplant Therapies, and Anti-Neoplastic Therapies) ................................................................. 102 6 Unmet Need and Opportunity ................................................................................................. 117 6.1 Overview ......................................................................................................................... 117 6.2 Lack of Randomized Clinical Trials ................................................................................. 120 6.2.1 Unmet Need ................................................................................................................ 120 6.2.2 Gap Analysis ............................................................................................................... 120 6.2.3 Opportunity ................................................................................................................. 121 6.3 No Consensus Regarding Clinical Trial Endpoints .......................................................... 121 6.3.1 Unmet Need ................................................................................................................ 121 6.3.2 Gap Analysis ............................................................................................................... 121 6.3.3 Opportunity ................................................................................................................. 122 6.4 Optimization of Prophylactic Measures ........................................................................... 122 6.4.1 Unmet Need ................................................................................................................ 122 6.4.2 Gap Analysis ............................................................................................................... 123 6.4.3 Opportunity ................................................................................................................. 123 6.5 Lack of Standardized Protocols for Established and Off-Label Therapies ....................... 124 6.5.1 Unmet Need ................................................................................................................ 124 6.5.2 Gap Analysis ............................................................................................................... 124 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 14 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Table of Contents 6.5.3 6.6 Opportunity ................................................................................................................. 125 Improved Treatment Outcomes for Patients Who Develop Toxicities .............................. 125 6.6.1 Unmet Need ................................................................................................................ 125 6.6.2 Gap Analysis ............................................................................................................... 126 6.6.3 Opportunity ................................................................................................................. 126 6.7 Desire for Treatments that Exhibit Longer-Lasting Efficacy Profiles ................................ 126 6.7.1 Unmet Need ................................................................................................................ 126 6.7.2 Gap Analysis ............................................................................................................... 127 6.7.3 Opportunity ................................................................................................................. 128 6.8 Management of SR-aGVHD Patients .............................................................................. 128 6.8.1 Unmet Need ................................................................................................................ 128 6.8.2 Gap Analysis ............................................................................................................... 129 6.8.3 Opportunity ................................................................................................................. 129 6.9 Management of Sclerotic cGVHD Patients ...................................................................... 129 6.9.1 Unmet Need ................................................................................................................ 129 6.9.2 Gap Analysis ............................................................................................................... 130 6.9.3 Opportunity ................................................................................................................. 130 6.10 Improved Prognosis for Patients with Lung Involvement ................................................. 131 6.10.1 Unmet Need ................................................................................................................ 131 6.10.2 Gap Analysis ............................................................................................................... 131 6.10.3 Opportunity ................................................................................................................. 132 7 Research and Development Strategies ................................................................................... 133 7.1 Overview ......................................................................................................................... 133 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 15 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Table of Contents 7.1.1 Improvement of Prophylactic Regimens ...................................................................... 133 7.1.2 Inhibition of T-Cell Proliferation and Activation ............................................................ 134 7.1.3 Adopting Treatments from Hematologic Indications..................................................... 135 7.1.4 Targeting Niche Subgroups Within GVHD ................................................................... 136 7.2 7.2.1 Current Clinical Trial Design............................................................................................ 137 Current Trial Designs are Dependent on the Stage Within the Treatment Algorithm That a Product is Targeting ................................................................................................ 137 7.2.2 Lack of Consensus on Clinical Endpoints in Current Trial Designs .............................. 138 7.2.3 Patient Exclusion Issues in Current Trial Designs ....................................................... 138 7.2.4 Current Trial Design of Key Pipeline Products ............................................................. 138 7.3 Future Clinical Trial Design ............................................................................................. 140 7.3.1 Future Trial Designs Need to Incorporate Randomization ........................................... 140 7.3.2 Future Trial Designs Need to Incorporate Conditioning Regimens and Hematological Patients ...................................................................................................................... 141 7.3.3 Companies Behind Off-Label Therapies Should Strategize to Conduct Randomized Studies ....................................................................................................................... 141 7.3.4 Design of Early-Phase Clinical Trials for Cellular and Gene Therapy Products Accommodates 2014 Guidance from the FDA ............................................................ 141 8 Pipeline Assessment............................................................................................................... 142 8.1 Overview ......................................................................................................................... 142 8.2 Promising Drugs in Clinical Development........................................................................ 143 8.2.1 Leukotac (inolimomab) ................................................................................................ 143 8.2.2 Begedina (BT 5/9) ....................................................................................................... 148 8.2.3 Budenofalk (budesonide) ............................................................................................ 151 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 16 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Table of Contents 8.2.4 ATG-Fresenius (EZ-2053) ........................................................................................... 154 8.2.5 Prochymal (remestemcel-L) ........................................................................................ 157 8.2.6 MultiStem (modified mesenchymal stem cells) ............................................................ 162 8.2.7 Uvadex (Extracorporeal Photophoresis) ...................................................................... 165 8.2.8 orBec (beclomethasone dipropionate) ......................................................................... 169 8.3 9 Innovative Early-Stage Approaches ................................................................................ 172 8.3.1 Targeting Regulatory T Cells ....................................................................................... 175 8.3.2 Mesenchymal Stem Cell Therapies ............................................................................. 176 8.3.3 Immunomodulatory Cell Surface Receptor Inhibitors ................................................... 177 8.3.4 IL-6 Inhibitors .............................................................................................................. 178 Pipeline and Off-Label Valuation Analysis............................................................................... 179 9.1 Clinical Benchmarking of Key Pipeline and Off-Label Drugs ........................................... 179 9.1.1 GVHD Prophylaxis ...................................................................................................... 179 9.1.2 Acute GVHD................................................................................................................ 182 9.1.3 Chronic GVHD ............................................................................................................ 186 9.2 Commercial Benchmarking of Key Pipeline and Off-Label Drugs .................................... 187 9.2.1 GVHD Prophylaxis ...................................................................................................... 188 9.2.2 Acute GVHD................................................................................................................ 190 9.2.3 Chronic GVHD ............................................................................................................ 192 9.3 Competitive Assessment ................................................................................................. 194 9.3.1 GVHD Prophylaxis ...................................................................................................... 194 9.3.2 Acute GVHD................................................................................................................ 195 9.3.3 Chronic GVHD ............................................................................................................ 197 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 17 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Table of Contents 9.4 Top-Line Five-Year Forecast........................................................................................... 199 9.4.1 US ............................................................................................................................... 204 9.4.2 5EU ............................................................................................................................. 208 10 Appendix................................................................................................................................. 212 10.1 Bibliography .................................................................................................................... 212 10.2 Abbreviations .................................................................................................................. 231 10.3 Methodology ................................................................................................................... 237 10.4 Forecasting Methodology ................................................................................................ 237 10.4.1 Diagnosed GVHD Patients .......................................................................................... 237 10.4.2 Percent Drug-Treated Patients .................................................................................... 238 10.4.3 Drugs Included in Each Therapeutic Class .................................................................. 238 10.4.4 Launch and Patent Expiry Dates ................................................................................. 239 10.4.5 General Pricing Assumptions ...................................................................................... 239 10.4.6 Individual Drug Assumptions ....................................................................................... 240 10.4.7 Generic Erosion .......................................................................................................... 247 10.4.8 Pricing of Pipeline Agents............................................................................................ 247 10.5 Physicians and Specialists Included in This Study .......................................................... 248 10.6 About the Authors ........................................................................................................... 250 10.6.1 Author ......................................................................................................................... 250 10.6.2 Reviewer ..................................................................................................................... 250 10.6.3 Epidemiologist ............................................................................................................. 251 10.6.4 Global Head of Healthcare .......................................................................................... 251 10.7 About GlobalData............................................................................................................ 252 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 18 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Table of Contents 10.8 1.1 Disclaimer ....................................................................................................................... 252 List of Tables Table 1: Steps Involved in the Development of aGVHD.................................................................................. 28 Table 2: Steps Involved in the Development of cGVHD .................................................................................. 29 Table 3: Grading System of Organ Involvement in aGVHD ............................................................................ 30 Table 4: Classification of Organ Involvement in cGVHD ................................................................................. 31 Table 5: Symptoms of aGVHD ....................................................................................................................... 31 Table 6: Symptoms of cGVHD ....................................................................................................................... 32 Table 7: Risk Factors and Comorbidities for GVHD ........................................................................................ 35 Table 8: 6MM, Sources of HSCT, aGVHD, and cGVHD Data Used for the Forecast ...................................... 39 Table 9: 6MM, Sources Not Used in the Epidemiological Analysis of GVHD ................................................... 46 Table 10: 6MM, Diagnosed Incident Cases of HSCTs, Both Sexes, All Ages, N, 2013–2023 .......................... 53 Table 11: 6MM, Diagnosed Incident Cases of Autologous HSCTs, Both Sexes, All Ages, N, 2013–2023 ....... 54 Table 12: 6MM, Diagnosed Incident Cases of Allogeneic HSCTs, Both Sexes, All Ages, N, 2013–2023 ......... 56 Table 13: 6MM, Diagnosed Incident Cases of aGVHD in Diagnosed Incident Cases of First Allogeneic HSCTs, Both Sexes, All Ages, N, 2013–2023 .............................................................................................. 58 Table 14: 6MM, Four-Year Diagnosed Prevalent Cases of aGVHD in Diagnosed Incident Cases of First Allogeneic HSCTs, All Ages, Both Sexes, N, 2013–2023................................................................ 60 Table 15: 6MM, Diagnosed Incident Cases of cGVHD in Diagnosed Incident Cases of First Allogeneic HSCTs, All Ages, Both Sexes, N, 2013–2023 .............................................................................................. 61 Table 16: 6MM, Five-Year Diagnosed Prevalent Cases of cGVHD in Diagnosed Incident Cases of First Allogeneic HSCTs, All Ages, Both Sexes, N, 2013–2023................................................................ 63 Table 17: Product Profile – Methylprednisolone ............................................................................................. 70 Table 18: Efficacy of Methylprednisolone in GVHD Studies ............................................................................ 71 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 19 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Table of Contents Table 19: SWOT analysis – Methylprednisolone, 2014................................................................................... 73 Table 20: Product Profile – Cyclosporine ....................................................................................................... 75 Table 21: Efficacy of Cyclosporine in GVHD Studies ...................................................................................... 76 Table 22: SWOT Analysis – Cyclosporine, 2014 ............................................................................................ 77 Table 23: Product Profiles – ATG Therapies .................................................................................................. 80 Table 24: Efficacy of ATG Therapies in GVHD ............................................................................................... 81 Table 25: SWOT Analysis – ATG Therapies, 2014 ......................................................................................... 82 Table 26: Product Profile – Biologics – TNFα Inhibitors .................................................................................. 85 Table 27: Efficacy of Anti-TNFα Therapies in GVHD ...................................................................................... 86 Table 28: Product Profiles – Biologics – IL-2Rα (CD25) Inhibitors .................................................................. 89 Table 29: Efficacy of IL-2Rα (CD25) Inhibitor Therapies in GVHD .................................................................. 90 Table 30: Product Profile – Biologics – Co-Stimulatory Blockers .................................................................... 93 Table 31: Efficacy of Co-Stimulatory Blocker Therapies in GVHD................................................................... 94 Table 32: Product Profile – Other Biologics (Campath/Lemtrada and Rituxan) ............................................... 96 Table 33: Efficacy of Other Biologic Therapies (Campath/Lemtrada and Rituxan) in GVHD ............................ 97 Table 34: Safety Profile – Off-Label Biologics Used in GVHD, 2014 ............................................................... 99 Table 35: SWOT Analysis – Biologics – TNFα Inhibitors, 2014 ..................................................................... 100 Table 36: SWOT Analysis – Biologics – IL-2Rα (CD25) inhibitors, 2014 ....................................................... 101 Table 37: SWOT Analysis – Biologics – Co-Stimulatory Blockers, 2014 ....................................................... 101 Table 38: SWOT Analysis – Biologics – Others, 2014 .................................................................................. 102 Table 39: Product Profile – Small Immunosuppressive Molecules – mTOR Inhibitors ................................... 104 Table 40: Efficacy of mTOR Inhibitors in GVHD ........................................................................................... 105 Table 41: Product Profile – Small Immunosuppressive Molecules – SOT Therapies ..................................... 106 Table 42: Efficacy of SOT Therapies in GVHD ............................................................................................. 107 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 20 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Table of Contents Table 43: Product Profile – Small Immunosuppressive Molecules – Anti-Neoplastic Therapies..................... 110 Table 44: Efficacy of Anti-Neoplastic Therapies in GVHD ............................................................................. 111 Table 45: Safety Profile – Small Immunosuppressive Molecules .................................................................. 113 Table 46: SWOT Analysis – Small Immunosuppressive Molecules – mTOR Inhibitors, 2014 ........................ 114 Table 47: SWOT Analysis – Small Immunosuppressive Molecules – SOT Therapies, 2014.......................... 115 Table 48: SWOT analysis – Small Immunosuppressive Molecules – Anti-Neoplastic Therapies, 2014 .......... 116 Table 49: Unmet Need and Opportunity in GVHD ........................................................................................ 119 Table 50: Clinical Trial Design of Key Pipeline Drugs for GVHD, July 2014 .................................................. 139 Table 51: GVHD – Late Stage Pipeline, 2013 .............................................................................................. 143 Table 52: Product Profile – Leukotac (inolimomab) ...................................................................................... 145 Table 53: Efficacy of Leukotac in GVHD ...................................................................................................... 147 Table 54: SWOT Analysis – Leukotac (inolimomab), 2014 ........................................................................... 148 Table 55: Product Profile – Begedina (BT 5/9) ............................................................................................. 149 Table 56: Efficacy of Begedina in GVHD ...................................................................................................... 150 Table 57: SWOT Analysis – Begedina (BT 5/9), 2014 .................................................................................. 151 Table 58: Product Profile – Budenofalk (budesonide) ................................................................................... 152 Table 59: SWOT Analysis – Budenofalk, 2014 ............................................................................................. 153 Table 60: Product Profile – ATG-Fresenius (EZ-2053) ................................................................................. 155 Table 61: Efficacy of ATG-Fresenius in GVHD (EZ-2053) ............................................................................ 156 Table 62: SWOT Analysis – ATG-Fresenius, 2014 ....................................................................................... 157 Table 63: Product Profile – Prochymal (remestemcel-L) ............................................................................... 160 Table 64: SWOT Analysis – Prochymal (remestemcel-L), 2014.................................................................... 162 Table 65: Product Profile – MultiStem (modified mesenchymal stem cells) ................................................... 163 Table 66: SWOT Analysis – MultiStem (modified mesenchymal stem cells) ................................................. 164 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 21 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Table of Contents Table 67: Product Profile – Uvadex (Extracorporeal Photophoresis) ............................................................. 167 Table 68: Efficacy of Uvadex in GVHD......................................................................................................... 168 Table 69: SWOT Analysis – Uvadex (Extracorporeal Photophoresis) ........................................................... 169 Table 70: Product Profile – orBec (beclomethasone dipropionate)................................................................ 171 Table 71: SWOT Analysis – orBec (beclomethasone proprionate), 2014 ...................................................... 172 Table 72: Early-Stage Pipeline Products for GVHD, July 2014 ..................................................................... 174 Table 73: Clinical Benchmarking for GVHD Prophylaxis, 2014 ..................................................................... 181 Table 74: Clinical Benchmarking for aGVHD, 2014 ...................................................................................... 185 Table 75: Clinical Benchmarking for cGVHD, 2014 ...................................................................................... 187 Table 76: Commercial Benchmarking for GVHD Prophylaxis, 2014 .............................................................. 189 Table 77: Commercial Benchmarking for aGVHD, 2014 ............................................................................... 191 Table 78: Commercial Benchmarking for cGVHD, 2014 ............................................................................... 193 Table 79: Top-Line Sales Forecasts ($m) for GVHD, 2013–2018 ................................................................. 201 Table 80: Key Events Impacting Sales for GVHD, 2013–2018...................................................................... 203 Table 81: Global GVHD Market – Drivers and Barriers, 2013–2018 ............................................................. 204 Table 82: Key Launch Dates, GVHD, 2013–2018 ........................................................................................ 239 Table 83: Key Patent Expiries, GVHD, 2013–2018....................................................................................... 239 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 22 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Table of Contents 1.2 List of Figures Figure 1: Schematic of HSCT ...................................................................................................................... 27 Figure 2: Schematic Flow Chart of the Derivation of the aGVHD and cGVHD Patient Population in the 6MM .................................................................................................................................................... 37 Figure 3: 6MM, Diagnosed Incident Cases of HSCTs , Both Sexes, All Ages, N, 2013–2023 ....................... 53 Figure 4: 6MM, Diagnosed Incident Cases of Autologous HSCTs, Both Sexes, All Ages, N, 2013–2023 ...... 55 Figure 5: 6MM, Diagnosed Incident Cases of Allogeneic HSCTs, Both Sexes, All Ages, N, 2013–2023 ...... 57 Figure 6: 6MM, Diagnosed Incident Cases of aGVHD in Diagnosed Incident Cases of First Allogeneic HSCTs, Both Sexes, All Ages, N, 2013–2023 ............................................................................... 59 Figure 7: 6MM, Four-Year Diagnosed Prevalent Cases of aGVHD in Diagnosed Incident Cases of First Allogeneic HSCTs, All Ages, Both Sexes, 2013–2023................................................................... 60 Figure 8: 6MM, Diagnosed Incident Cases of cGVHD in Diagnosed Incident Cases of First Allogeneic HSCTs, All Ages, Both Sexes, N, 2013–2023 ............................................................................... 62 Figure 9: 6MM, Five-Year Diagnosed Prevalent Cases of cGVHD in Diagnosed Incident Cases of First Allogeneic HSCTs, All Ages, Both Sexes, N, 2013–2023 .............................................................. 63 Figure 10: Trends in aGVHD Management in the 6MM, 2014......................................................................... 68 Figure 11: Trends in cGVHD Management in the 6MM, 2014 ......................................................................... 69 Figure 12: Competitive Assessment of GVHD Prophylaxis Off-Label Therapies and Late-Stage Pipeline Agents, 2013–2018 .................................................................................................................... 195 Figure 13: Competitive Assessment of aGVHD Off-Label Therapies and Late-Stage Pipeline Agents, 2013– 2018 ........................................................................................................................................... 197 Figure 14: Competitive Assessment of cGVHD Off-Label Therapies and Late-Stage Pipeline Agents, 2013– 2018 ........................................................................................................................................... 199 Figure 15: Global Sales for GVHD by Region and GVHD Indication, 2013–2018 .......................................... 202 Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 23 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Introduction 2 Introduction Graft-versus-host disease (GVHD) is an orphan indication with a poor prognosis and high mortality rates. It is a complication of hematopoietic stem cell transplantation (HSCT), and takes different forms, depending on the time of disease manifestation and organ localization. As GVHD pathogenesis remains largely elusive, the current treatments used for its management are not GVHD-specific, but rather, are off-label therapies borrowed from immunological and hematological indications. However, the GVHD pipeline is rich and diverse, and promises a big change in the landscape of the GVHD market. 2.1 Catalyst Despite the vast array of available off-label therapies (approximately 30) for the treatment and/or prevention of GVHD, very few of these therapies have been tested in large randomized clinical trials. This has resulted in vague treatment recommendations and many patients being enrolled in institutional clinical trials. The only available standard of care is intravenous (IV) methylprednisolone. However, it fails to produce a complete response (CR) in more than 50% of treated patients. As a result, steroid-refractory patient subgroups face a poor prognosis, with a deteriorating quality of life (QoL). This problem is further compounded by the fact that second- and third-line treatments can vary from country to country across the six major markets (6MM) (US, France, Germany, Italy, Spain, and UK), and also between different medical institutions in the same country. Over GlobalData’s 2013–2018 forecast period, the main drivers of growth in the GVHD market include the increasing numbers of allogeneic HSCTs and the increasing use of marketed and offlabel biologic therapies across the 6MM. Sanofi/Genzyme is a key player in the GVHD market, with EU-approved Thymoglobulin (antithymocyte globulin [rabbit]) and the off-label biologic therapy, Campath/Lemtrada, which infiltrate the prophylaxis, acute GVHD (aGVHD), and chronic GVHD (cGVHD) setting. Still, Johnson & Johnson’s (J&J’s) Remicade (infliximab) has gained a significant share of the aGVHD patient group, as it is one of the few drugs that is effective in GVHD with gastrointestinal (GI) involvement. Meanwhile, gaining more and more ground in the cGVHD setting is Roche’s Rituxan (rituximab), which GlobalData estimates will be one of the best-selling biologics by value in GVHD, in the US by 2018. Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 24 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 Introduction 2.2 Related Reports GlobalData (2014). EpiCast Report: Graft-Versus-Host Disease – Epidemiology Forecast to 2023, June 2014, GDHCER064-14 GlobalData (2014). OpportunityAnalyzer: Chronic Lymphocytic Leukemia – Opportunity Analysis and Forecasts to 2018, June 2014, GDHC017POA GlobalData (2014). PharmaPoint: Ulcerative Colitis – Global Drug Forecast and Market Analysis to 2022, February 2014, GDHC80PIDR GlobalData (2014). PharmaPoint: Crohn’s Disease – Global Drug Forecast and Market Analysis to 2022, January 2014, GDHC77PIDR GlobalData (2013). OpportunityAnalyzer: Acute Myeloid Leukemia (AML) – Opportunity Analysis and Forecasts to 2017, August 2013, GDHC003POA GlobalData (2013). PharmaPoint: Chronic Myeloid Leukemia (CML), Global Drug Forecast and Market Analysis to 2022, April 2013, GDHC103PIDR 2.3 Upcoming Related Reports GlobalData (2014). PharmaSphere – Emerging Biotechnologies: Stem Cell Therapy, August 2014, GDHC012PSR GlobalData (2014). OpportunityAnalyzer: - Non Hodgkin B cell Lymphoma, Opportunity Analysis and Forecasts to 2018, July 2014, GDHC035POA Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 25 GRAFT-VERSUS-HOST DISEASE – OPPORTUNITY ANALYSIS AND FORECASTS TO 2018 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, San Francisco, Boston, London, India, Korea, Japan, Singapore, and Australia. 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. Graft-Versus-Host Disease – Opportunity Analysis and Forecasts to 2018 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. 252