Synribo (Chronic Myeloid Leukemia) Forecast and Market Analysis to 2022 GDHC1141DFR / Published May 2013
Executive Summary Synribo (omacetaxine mepesuccinate): Key Metrics in CML Markets 2012 Synribo Sales US 7MM* Key events (2013 2022) Launch of Iclusig in the US in 2013 Launch of generic imatinib in the US in 2015 2022 Synribo Sales US 7MM* Source: GlobalData $1.4m $1.4m Level of Impact 7MM= US, Japan, UK, France, Germany, Spain and Italy. Synribo is not expected to launch in any countries outside the US. $20.6m $20.6m What Do the Physicians Think? Our experts believe that the most promising new market entrant is Ariad s Iclusig (ponatinib). Although it is highly efficacious, they expect its use to be limited to later lines of therapy as a result of its premium price and associated toxicities. Ponatinib is a really good drug and I think that it s the one that has a chance to really move up. Because I think a lot of [physicians], they are thinking about it for people who have T315I mutations but it works on almost all the mutations. So I think there is going to be a move to kind of use that as a salvage therapy, especially for people Sales for Synribo in the Global CML Market Sales of Teva s Synribo (omacetaxine mepesuccinate) in the CML therapeutics market in the US are expected to increase from $1.4m in 2012 to $20.6m in 2022 at a CAGR of 30.6%. Synribo is not expected to launch in the other major markets over this forecast period. The major drivers of Synribo sales over this forecast period will include: Minimal use of Synribo by patients who never responded to TKI therapy or are intolerant to TKIs. A continually growing prevalence of CML due to improvements in overall survival rates Barriers to the growth of Synribo in the CML therapeutics market will include: Competition from Bosulif and Iclusig for market share in refractory CML patients Failure to seek regulatory approval of Synribo in the European countries and Japan who have started on dasatinib and nilotinib and don t do well. They will go to ponatinib. US Key Opinion Leader, February 2013 Ponatinib is a very active drug against all mutations, and it has a very, very good chance for third-line, of course, but also [for] second-line treatment. The study for firstline treatment is ongoing, that means I expect some more [use] in first-line as well. But then, having four drugs available for first-line treatment it really depends on the economics. 5EU Key Opinion Leader, February 2013 Key opinion leaders in the 7MM believe that the safety and cost will be the most critical factors influencing future prescribing patterns. In the next five years, the most important factors will be the side effects and the cost [of a drug] more than the efficacy, because all these drugs are very effective. 5EU Key Opinion Leader, January 2013 Physician concerns regarding Synribo s toxicity, and limited appeal of its inconvenient route of administration to patients Page 2 GDHC1141DFR/ Published MAY 2013
Executive Summary Physicians are eager for the launch of generic imatinib. They believe that although other therapies are stronger, the cost savings associated with generic imatinib will make it the drug of choice for low- to intermediate-risk newly diagnosed CP-CML patients. In many markets, particularly in the 5EU, they expect the use of generic imatinib to be mandated by payers. I think that when you calculate the prevalence of CML in the world, I think that [using generic imatinib in newly diagnosed CML patients] is the right decision. You can help more patients when you use the cheaper drug, in total. But of course, the individual patient would benefit from the more expensive and efficacious drug; but the worldwide population of CML patients will benefit from the cheaper drug because more patients can be treated with the cheaper drug. That s the responsibility we all have. 5EU Key Opinion Leader, February 2013 The discontinuation of TKI therapy is the future of CML, and something highly desired by patients. The target for the 21st century must be to stop a tyrosine kinase inhibitor in a way that a person doesn t need to take it for the rest of their life. So all attention focuses on a) how you can increase the proportion of patients who achieve a complete, durable, molecular response and b) what additional measures you can take to ensure that eventually a TKI can be stopped. 5EU Key Opinion Leader, January 2013 Currently, there is no best sequence of TKIs to prescribe for CML patients. More long-term follow-up data is needed to justify routinely prescribing second- or third-generation TKIs for newly diagnosed CP-CML patients rather than Gleevec. There is still not enough data for us to recommend any specific treatment other than just tyrosine kinase inhibitors for upfront therapy for CML. Especially regarding an increase in survival. US Key Opinion Leader, February 2013 Page 3 GDHC1141DFR/ Published MAY 2013
Table of Contents 1 Table of Contents 1 Table of Contents... 4 1.1 List of Tables... 6 1.2 List of Figures... 6 2 Introduction... 7 2.1 Catalyst... 7 2.2 Related Reports... 7 2.3 Upcoming Related Reports... 8 3 Disease Overview... 9 3.1 Etiology and Pathophysiology... 9 3.1.1 Etiology... 9 3.1.2 Pathophysiology... 10 3.1.3 Clinical Staging... 11 3.1.4 Prognosis... 13 3.1.5 Quality of Life... 14 3.2 Symptoms... 15 4 Disease Management... 16 4.1 Global Trends... 16 4.1.1 Treatment Overview... 16 4.1.2 Diagnostic Tests... 19 4.1.3 Genetic Testing... 20 4.1.4 Monitoring Patient Response to Treatment... 22 4.1.5 Future Directions: Discontinuation Therapy... 25 5 Competitive Assessment... 27 5.1 Overview... 27 5.2 Strategic Competitor Assessment... 28 6 Product Profile - Synribo (omacetaxine mepesuccinate)... 31 6.1 Overview... 31 Page 4 GDHC1141DFR / Published MAY 2013
Table of Contents 6.2 Efficacy... 33 6.3 Safety... 33 6.4 SWOT Analysis... 34 6.5 Forecast... 35 7 Appendix... 36 7.1 Bibliography... 36 7.2 Abbreviations... 39 7.3 Methodology... 42 7.4 Forecasting Methodology... 42 7.4.1 Diagnosed CML patients... 42 7.4.2 Drug-treated Patients on X Line of Therapy... 43 7.4.3 General Pricing Assumptions... 43 7.4.4 Individual Drug Assumptions... 44 7.4.5 Generic Erosion... 44 7.5 Physicians and Specialists Included in this Study... 45 7.6 Survey of High Prescribing Physicians... 47 7.7 About the Authors... 48 7.7.1 Authors... 48 7.7.2 Epidemiologists... 49 7.7.3 Global Director of Epidemiology and Clinical Trials Analysis... 50 7.7.4 Global Head of Healthcare... 51 7.8 About GlobalData... 52 7.9 Contact Us... 52 7.10 Disclaimer... 52 Page 5 GDHC1141DFR / Published MAY 2013
Table of Contents 1.1 List of Tables Table 1: The Staging of CML as Defined by Commonly Used Staging Systems... 12 Table 2: Prognostic Scoring Systems for CML... 13 Table 3: Common Symptoms of CML by Disease Phase... 15 Table 4: Most Commonly Followed Treatment Guidelines for CML... 18 Table 5: Table 6: Most Prescribed First-Line Therapies for CP, AP and BP CML in the Global Markets, 2013... 18 Suggested Treatments for CML Patients with Selected BCR-ABL Kinase Domain Mutations... 21 Table 7: CML Response Types, Criteria, and Corresponding Tests... 23 Table 8: Leading Treatments for Chronic Myeloid Leukemia, 2013... 30 Table 9: Product Profile Synribo... 32 Table 10: Synribo SWOT Analysis, 2013... 34 Table 11: Global Sales Forecasts ($m) for Synribo in CML, 2012 2022... 35 Table 12: Physicians Surveyed, by Country... 47 1.2 List of Figures Figure 1: Translocation of Chromosomes 9 and 22... 9 Figure 2: Comparison of Normal and Leukemia Blood Cells... 10 Page 6 GDHC1141DFR / Published MAY 2013
Introduction 2 Introduction 2.1 Catalyst The launch of Novartis BCR-ABL inhibitor Gleevec (imatinib) in 2001 forever changed the treatment of chronic myeloid leukemia (CML). With Gleevec, and later the second-generation TKIs, BMS Sprycel (dasatinib) and Novartis Tasigna (nilotinib), CML has become less of a death sentence and more of a chronic, manageable condition. The CML market has grown as a result of this steadily increasing disease prevalence, and the high cost of branded TKIs places a heavy financial burden on patients and global healthcare systems. The effects of this burden will have a major impact on the future CML market. The sustained and escalating costs of branded TKI therapy have left payers, physicians and patients anxiously awaiting the launch of generic imatinib. Swift erosion of Gleevec sales will follow, and physicians will be left with the question of whether to prescribe second-generation TKIs for newly diagnosed patients, or the more cost-effective generic Gleevec. Ultimately, the launch and uptake of generic imatinib will be the primary driver of the decreasing size of the global CML market. New entrants Pfizer s Bosulif (bosutinib) and Ariad s Iclusig (ponatinib) will be welcome treatment options for patients who are refractory to or intolerant of Gleevec, Sprycel and Tasigna. In light of the aforementioned fiscal constraints, these drugs will be predominantly prescribed in later lines of therapy, restricting their ability to compensate for the market s loss of Gleevec sales. 2.2 Related Reports GlobalData (2013). Chronic Myeloid Leukemia - United States Drug Forecast and Market Analysis to 2022. GDHC1082CFR GlobalData (2013). Chronic Myeloid Leukemia - United Kingdom Drug Forecast and Market Analysis to 2022. GDHC1087CFR GlobalData (2013). Chronic Myeloid Leukemia - France Drug Forecast and Market Analysis to 2022. GDHC1083CFR GlobalData (2013). Chronic Myeloid Leukemia - Germany Drug Forecast and Market Analysis to 2022. GDHC1084CFR GlobalData (2013). Chronic Myeloid Leukemia - Italy Drug Forecast and Market Analysis to 2022. GDHC1085CFR Page 7 GDHC1141DFR / Published MAY 2013
Introduction GlobalData (2013). Chronic Myeloid Leukemia - Spain Drug Forecast and Market Analysis to 2022. GDHC1086CFR GlobalData (2013). Chronic Myeloid Leukemia - Japan Drug Forecast and Market Analysis to 2022. GDHC1088CFR GlobalData (2013). Gleevec (Chronic Myeloid Leukemia) - Forecast and Market Analysis to 2022. GDHC1136DFR GlobalData (2013). Sprycel (Chronic Myeloid Leukemia) - Forecast and Market Analysis to 2022. GDHC1137DFR GlobalData (2013). Tasigna (Chronic Myeloid Leukemia) - Forecast and Market Analysis to 2022. GDHC1138DFR GlobalData (2013). Bosulif (Chronic Myeloid Leukemia) - Forecast and Market Analysis to 2022. GDHC1139DFR GlobalData (2013). Iclusig (Chronic Myeloid Leukemia) - Forecast and Market Analysis to 2022. GDHC1140DFR GlobalData (2013). Chronic Myeloid Leukemia - Current and Future Players. GDHC1011FPR Page 8 GDHC1141DFR / Published MAY 2013
Appendix 7.8 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, Boston, London, India and Singapore. 7.10 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. Page 52 GDHC1141DFR / Published MAY 2013