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Chronic Myeloid Leukemia (CML) United States Drug Forecast and Market Analysis to 2022

GDHC1082CFR / Published April 2013

Executive Summary

© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. GDHC1082CFR / Published APR 2013

Sales for CML in the United States

The US CML market was valued at an estimated $1.60

billion in 2012. GlobalData expects the market to decline

to $1.03 billion by 2022, at a negative CAGR of 4.3%.

Peak sales of $2.13 billion are expected in 2014. Among

the 7MM, the US has the largest number of prevalent

cases of CML and is the largest global CML market.

Major drivers of CML market growth over this forecast

period will include:

An anticipated increase in the number of prevalent

cases of CML, resulting in a larger pool of treated

patients

Continuing uptake of premium-priced second and

third-generation TKIs, particularly in later lines of

therapy

Major barriers to the growth of the CML market in the US

will include:

Erosion of sales of branded drugs, particularly

Gleevec and Sprycel, following the entrance of

generic competition

Government and private payers’ attempt to

encourage the prescription of generics instead of

new, more expensive TKIs such as Iclusig and

Bosulif

Patient non-compliance with their medication due to

the high cost of therapy

The following figure shows the breakdown of sales of

CML therapeutics market by brand in the US from 2012

to 2022.

Sales for CML Therapeutics in the United States by Brand, 2012–2022

Source: GlobalData

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.

52.7%

25.2%

21.8%0.3% 0.1%

Gleevec Sprycel Tasigna Bosulif Iclusig Synribo

2012Total: $1,598m

5.5% 2.8%

46.0%

8.0%

35.7%

2.0%

Gleevec Sprycel Tasigna Bosulif Iclusig Synribo

2022Total: $1,026m

Executive Summary


“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

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 first-

line 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

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

Table of Contents


1 Table of Contents

1 Table of Contents ............................................................................................................... 4

1.1 List of Tables ............................................................................................................... 8

1.2 List of Figures ............................................................................................................. 9

2 Introduction ....................................................................................................................... 10

2.1 Catalyst ..................................................................................................................... 10

2.2 Related Reports ........................................................................................................ 10

2.3 Upcoming Related Reports ........................................................................................ 11

3 Disease Overview ............................................................................................................. 12

3.1 Etiology and Pathophysiology .................................................................................... 12

3.1.1 Etiology ............................................................................................................... 12

3.1.2 Pathophysiology.................................................................................................. 13

3.1.3 Clinical Staging ................................................................................................... 15

3.1.4 Prognosis ............................................................................................................ 16

3.1.5 Quality of Life ...................................................................................................... 17

3.2 Symptoms ................................................................................................................. 17

4 Disease Management ....................................................................................................... 19

4.1 Global Trends ........................................................................................................... 19

4.1.1 Treatment Overview ............................................................................................ 19

4.1.2 Diagnostic Tests ................................................................................................. 21

4.1.3 Genetic Testing ................................................................................................... 22

4.1.4 Monitoring Patient Response to Treatment .......................................................... 24

4.1.5 Future Directions: Discontinuation Therapy ......................................................... 27

4.2 US ........................................................................................................................... 28

4.2.1 Diagnosis and Monitoring .................................................................................... 28

4.2.2 Clinical Practice .................................................................................................. 29

4.2.3 Genetic Testing ................................................................................................... 30

Table of Contents


5 Competitive Assessment ................................................................................................... 31

5.1 Overview ................................................................................................................... 31

5.2 Strategic Competitor Assessment .............................................................................. 31

5.3 Product Profiles- Major Brands .................................................................................. 34

5.3.1 Gleevec (imatinib) ............................................................................................... 34

5.3.2 Sprycel (dasatinib) .............................................................................................. 39

5.3.3 Tasigna (nilotinib) ................................................................................................ 44

5.3.4 Bosulif (bosutinib) ............................................................................................... 49

5.3.5 Iclusig (ponatinib) ................................................................................................ 54

5.3.6 Synribo (omacetaxine mepesuccinate) ................................................................ 58

5.3.7 Minor Therapeutic Classes .................................................................................. 62

6 Opportunity and Unmet Need ............................................................................................ 64

6.1 Overview ................................................................................................................... 64

6.2 Unmet Need: A Drug that Can Cure CML .................................................................. 65

6.3 Unmet Need: Lower Annual Cost of Therapy ............................................................. 66

6.4 Unmet Need: Treatments for Patients Who Have Primary Resistance to or are

Refractory to TKIs ..................................................................................................... 67

6.5 Unmet Need: More Efficacious Treatments for AP and BP CML ................................ 67

6.6 Unmet Need: Therapies with Fewer Chronic Side Effects .......................................... 68

6.7 Unmet Need: Better Compliance from Patients on Long-Term Oral Therapy .............. 68

6.8 Unmet Need: Methods of Determining the Optimal Therapy for a Patient ................... 69

6.9 Opportunity: Exploration into Discontinuation Therapy ............................................... 69

6.10 Opportunity: Companion Devices to Enhance Patient Adherence to Oral Therapy ..... 70

6.11 Opportunity: Therapies with BCR-ABL Independent MOAs ........................................ 70

6.12 Opportunity: Extended-Release Formulations of TKIs ................................................ 71

6.13 Opportunity: Biomarkers to Identify the Optimal Therapy for a Given Patient .............. 71

7 Pipeline Assessment......................................................................................................... 72

7.1 Overview ................................................................................................................... 72

7.2 Innovative Early-Stage Approaches ........................................................................... 73

Table of Contents


7.2.1 Project 1: The Wnt Signaling Pathway ................................................................. 74

7.2.2 Project 2: Jak2 Inhibitors ..................................................................................... 75

7.2.3 Project 3: Grb-2................................................................................................... 76

7.2.4 Case Study: Smoothened Inhibitors .................................................................... 76

8 Market Outlook ................................................................................................................. 78

8.1 United States ............................................................................................................ 78

8.1.1 Forecast.............................................................................................................. 78

8.1.2 Key Events ......................................................................................................... 81

8.1.3 Drivers and Barriers ............................................................................................ 81

9 Appendix .......................................................................................................................... 84

9.1 Bibliography .............................................................................................................. 84

9.2 Abbreviations ............................................................................................................ 90

9.3 Methodology ............................................................................................................. 93

9.4 Forecasting Methodology .......................................................................................... 93

9.4.1 Diagnosed CML patients ..................................................................................... 93

9.4.2 Drug-treated Patients on X Line of Therapy ......................................................... 94

9.4.3 Drugs Included in Each Therapeutic Class .......................................................... 94

9.4.4 Launch and Patent Expiry Dates ......................................................................... 95

9.4.5 General Pricing Assumptions .............................................................................. 95

9.4.6 Compliance Assumptions for Oral TKIs ............................................................... 96

9.4.7 Individual Drug Assumptions ............................................................................... 96

9.4.8 Generic Erosion .................................................................................................. 99

9.5 Physicians and Specialists Included in this Study .................................................... 100

9.6 Survey of High Prescribing Physicians ..................................................................... 101

9.7 About the Authors ................................................................................................... 102

9.7.1 Authors ............................................................................................................. 102

9.7.2 Epidemiologists ................................................................................................. 103

9.7.3 Global Director of Epidemiology and Clinical Trials Analysis .............................. 104

Table of Contents


9.7.4 Global Head of Healthcare ................................................................................ 105

9.8 About GlobalData ................................................................................................... 106

9.9 Contact Us ............................................................................................................. 106

9.10 Disclaimer .............................................................................................................. 106

Table of Contents


1.1 List of Tables

Table 1: The Staging of CML as Defined by Commonly Used Staging Systems .................... 15

Table 2: Prognostic Scoring Systems for CML ...................................................................... 16

Table 3: Common Symptoms of CML by Disease Phase ...................................................... 18

Table 4: Most Commonly Followed Treatment Guidelines for CML ....................................... 20

Table 5: Most Prescribed First-Line Therapies for CP, AP and BP CML in the Global Markets,

2013 ....................................................................................................................... 21

Table 6: Suggested Treatments for CML Patients with Selected BCR-ABL Kinase Domain

Mutations ................................................................................................................ 24

Table 7: CML Response Types, Criteria, and Corresponding Tests ...................................... 25

Table 8: Leading Treatments for Chronic Myeloid Leukemia, 2013 ....................................... 33

Table 9: Product Profile – Gleevec ....................................................................................... 35

Table 10: Hematologic and Cytogenetic Reponses to Gleevec in Newly Diagnosed CML

Patients .................................................................................................................. 37

Table 11: Gleevec SWOT Analysis, 2013 ............................................................................... 38

Table 12: Product Profile – Sprycel ........................................................................................ 40

Table 13: Hematologic and Cytogenetic Reponses to Sprycel in Imatinib Resistant or Intolerant

Advanced Phase CML ............................................................................................ 41

Table 14: Sprycel SWOT Analysis, 2013 ................................................................................ 43

Table 15: Product Profile – Tasigna ....................................................................................... 45

Table 16: Molecular and Cytogenetic Responses of Tasigna Compared with Gleevec in Newly

Diagnosed Ph+ CML in CP ..................................................................................... 46

Table 17: Tasigna SWOT Analysis, 2013 ............................................................................... 48

Table 18: Product Profile – Bosulif ......................................................................................... 50

Table 19: Bosulif SWOT Analysis, 2013 ................................................................................. 53

Table 20: Product Profile – Iclusig .......................................................................................... 55

Table 21: Iclusig SWOT Analysis, 2013 .................................................................................. 58

Table 22: Product Profile – Synribo ........................................................................................ 60

Table 23: Synribo SWOT Analysis, 2013 ................................................................................ 62

Table 24: Summary of Minor Therapeutic Classes, 2013 ........................................................ 63

Table of Contents


Table 25: Overall Unmet Needs – Current Level of Attainment ............................................... 65

Table 26: Early-stage Pipeline Projects in CML ...................................................................... 74

Table 27: Global Sales Forecasts ($m) for CML in the US, 2012–2022 .................................. 79

Table 28: Key Events Impacting Sales of CML Therapeutics in the United States, 2013 ......... 81

Table 29: CML Market in the United States – Drivers and Barriers, 2013 ................................ 81

Table 30: Key Launch Dates .................................................................................................. 95

Table 31: Key Patent Expiries ................................................................................................ 95

Table 32: Physicians Surveyed, by Country ......................................................................... 101

1.2 List of Figures

Figure 1: Translocation of Chromosomes 9 and 22 ............................................................... 13

Figure 2: Comparison of Normal and Leukemia Blood Cells .................................................. 14

Figure 3: Sales for CML Therapeutics in the United States by Brand, 2012–2022 ................. 80

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 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

GlobalData (2013). Chronic Myeloid Leukemia - Spain Drug Forecast and Market Analysis to

2022. GDHC1086CFR

Introduction


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. GDHC11340FR

GlobalData (2013). Synribo (Chronic Myeloid Leukemia) - Forecast and Market Analysis to

2022. GDHC1141DFR

GlobalData (2013). Chronic Myeloid Leukemia - Current and Future Players. GDHC1011FPR

Appendix

© GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form. Page 106 GDHC1082CFR / Published APR 2013

9.8 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.

9.10 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.

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