View
213
Download
0
Category
Preview:
Citation preview
REFERENCE CODE GDHC017POA | PUBLICAT ION DATE JUNE 2014
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 2 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
Executive Summary
The table below presents the key metrics for
chronic lymphocytic leukemia (CLL) in the six
major pharmaceutical markets (6MM) (US, France,
Germany, Italy, Spain, and UK), during the forecast
period from 2013–2018.
Chronic Lymphocytic Leukemia: Key Metrics in the Six Major Pharmaceutical Markets, 2013–2018
2013 Epidemiology
Incident Population 37, 795
2013 Market Sales
US $ 821m
5EU $571m
Total $1.4bn
Key Events (2013–2018) Level of Impact
Loss of MabThera (rituximab) marketing exclusivity in the EU ↓
US approval of Gazyva (obinutuzumab) for first-line CLL in 2013 (EU approval expected in 2014)
↑↑
US and EU approval of Imbruvica (ibrutinib) for relapsed/refractory CLL in 2014
↑↑↑
US and EU approval of idelalisib for relapsed/refractory CLL in 2014 ↑↑↑
Loss of Levact/Treanda (bendamustine) marketing exclusivity in 2014 in the EU, and in 2015 in the US
↓↓
US and EU approval of Imbruvica in the first-line setting in 2016 ↑
US and EU approval of IPI-145 for relapsed/refractory CLL in 2016 ↑
US and EU approval of idelalisib in the first-line setting in 2017 ↑
2018 Market Sales
US $2bn
5EU $1.3bn
Total $3.3bn Source: GlobalData 5EU = France, Germany, Italy, Spain, and UK
New Entrants will Drive Strong Growth in the US and EU CLL Market from 2013–2018
GlobalData estimates the CLL market in the US
and 5EU (France, Germany, Italy, Spain, and UK)
in 2013 to be valued at $1.4 billion. The market is
defined as sales from branded drugs, including
Rituxan (rituximab), Arzerra (ofatumumab),
Treanda (bendamustine) and Gazyva
(obinutuzumab). Although there are more incident
cases of CLL in the 5EU, the majority of sales in
2013, $821m (59%), were generated in the US due
to higher drug prices. Sales in the 5EU were
estimated to be $571m (41%) in 2013.
By the end of the forecast period in 2018, the
market is expected to grow to $3.3 billion at a
Compound Annual Growth Rate (CAGR) of 18.8%.
GlobalData expects the launch of premium-priced
new therapies, such as Gazyva, Imbruvica
(ibrutinib), idelalisib, and IPI-145, for CLL patients
with high unmet needs will drive overall market
growth in the 6MM covered in this report during the
forecast period.
Major drivers of the CLL market in the US and 5EU
during the forecast period will include:
Rapid uptake of four new branded drugs,
including Gazyva, Imbruvica, idelalisib, and
IPI-145
Premium pricing for new branded drugs, as
they address high unmet needs (as already
observed with Imbruvica in the US)
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 3 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
Executive Summary
Dose-continuous regimens of the new targeted
therapies, which means that patients will
remain on drugs longer, instead of receiving a
fixed course of therapy
Use of a combination approach to maximize
the efficacy of new drugs, resulting in
increased sales of branded drugs
Increased total treated patient pool due to
fewer patients being enrolled in clinical trials
and more patients being treated with branded
drugs
A rapidly aging population, which will increase
CLL incidence
Barriers to the growth of the CLL market in the US
and 5EU during the forecast period will include:
Pressure for cost-consciousness, which will
limit premium pricing for new entrants in the
5EU
The loss of marketing exclusivity for Treanda in
CLL (2014 in the EU, and 2015 in the US),
which will occur during a time when its use, in
combination with new drugs, is expected to
grow substantially
The figure below illustrates the global sales for CLL
in the US and 5EU during the forecast period from
2013–2018.
Global Sales for CLL By Region (US and 5EU), 2013–2018
59%
41%
Global CLL Market 2013$1.4bn
60%
40%
US
5EU
Global CLL Market 2018$3.3bn
Source: GlobalData
Imbruvica and Idelalisib will Undergo Rapid Uptake in the Second-Line, Driven by the Lack of Standard Treatment Options and High Unmet Need in this Patient Population
Historically, CLL patients who did not experience a
long response after initial therapy had limited
therapeutic options and a high degree of clinical
unmet need for second-line treatment that could
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 4 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
Executive Summary
extend survival after primary relapse. Because of
the lack of standard-of-care treatment options,
many relapsed/refractory patients are enrolled in
clinical trials for investigative therapies. However,
with the anticipated launch of Imbruvica and
idelalisib in the US and EU in 2014, GlobalData
expects that the treatment of these patients will
undergo significant change. In phase II and III
trials, Imbruvica and idelalisib have shown strong
efficacy and tolerability, which, in correlation with
the high level of unmet need in this patient
population, will drive very rapid uptake of both
drugs. Furthermore, the completion of trials
studying the combination of these new agents with
BR (bendamustine and Rituxan), as well as the
results of studies of Imbruvica and idelalisib in the
first-line treatment of elderly patients, which are
expected by 2016, will contribute towards
establishing these two drugs as the most
successful branded therapies for CLL. With total
combined sales of $2 billion in 2018, GlobalData
forecasts Imbruvica and idelalisib to capture more
than 60% of the total CLL market by then.
Second-to-Market Idelalisib will become the Market Leader in the Relapsed/Refractory Setting in 2018
Despite the fact that idelalisib will launch in the US
in Q3 2014, several months after the approval of
Imbruvica by the Food and Drug Administration
(FDA) in February 2014, GlobalData foresees that
idelalisib will eventually emerge as the market
leader in the relapsed/refractory setting by 2018. In
contrast to Imbruvica, which initially launched as a
monotherapy, idelalisib will be used in combination
with the standard CLL backbone agent, Rituxan.
The ability to combine idelalisib with Rituxan
represents a safer alternative for
relapsed/refractory patients who are unfit to
receive chemoimmunotherapy regimens.
GlobalData believes this will provide idelalisib with
a significant advantage over Imbruvica, which has
demonstrated an inhibitory effect on anti-CD20-
mediated cytotoxicity, suggesting that it may be
incompatible in combination with anti-CD20
antibodies such as Rituxan. Furthermore, safety
concerns regarding Imbruvica’s interaction with
anticoagulants and antiplatelet drugs will further
limit its uptake among elderly patients. In the US,
GlobalData foresees idelalisib’s patient share in
the relapsed/refractory setting to overtake
Imbruvica’s share by 2017. Imbruvica’s sales will,
however, remain higher during the forecast period
because of its premium pricing over idelalisib. In
Europe, although growing pressure to reduce
healthcare expenditures is likely to constitute a
hurdle to obtaining premium pricing for an agent
being used in combination with a drug that is
already expensive, such as Rituxan, GlobalData
believes that idelalisib will capture both greater
patient and market shares than Imbruvica, as
Imbruvica will not have the same time-to-market
advantage in Europe. In 2018, sales of Imbruvica
and idelalisib in the 6MM are forecast to reach $1b
and $984m, respectively.
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 5 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
Executive Summary
The figure below provides a competitive
assessment of the key marketed and pipeline
drugs in the first-line treatment of CLL.
Competitive Assessment of Key Marketed and Pipeline Drugs – First-Line CLL
2.50
3.00
3.50
2.50 3.00 3.50
Com
mer
cial
Sco
re
Arzerra
Gazyva
Chl+R FCR Imbruvica
idelalisib
Clinical Score
Source: GlobalData
The figure below provides a competitive
assessment of the key marketed and pipeline
drugs in the treatment of relapsed/refractory CLL.
Competitive Assessment of Key Marketed and Pipeline Drugs – Relapsed/Refractory CLL
2.0
2.5
3.0
3.5
2.0 2.5 3.0 3.5 4.0
Com
mer
cial
Scor
e
Arzerra
BR
IPI-145
Imbruvicaidelalisib
Clinical Score Source: GlobalData
Uptake of the New Agents Will be Slower in the First-Line Setting, Limited by Reduced Uptake Among Younger CLL Patients
GlobalData expects that the uptake of the new
agents, idelalisib and Imbruvica, will be slower in
the first-line setting, where high rates of use of the
gold-standard FCR (fludarabine,
cyclophosphamide, and Rituxan) regimen among
young, fit CLL patients will limit the ability of these
new agents to penetrate the first-line market.
GlobalData’s primary research revealed high levels
of satisfaction with the safety and efficacy profile of
FCR in this patient population, and so far, drug
developers have largely refrained from making any
direct comparisons with FCR in their clinical
development programs. Instead, GlobalData
anticipates that these new agents will be targeted
at the elderly patient population. However, data
from their late-stage trials will not be available until
June 2015 (Imbruvica) and June 2016 (idelalisib).
GlobalData expects that Gazyva, which is already
approved in the first-line setting in the US, will also
have a slower uptake, as its approval in
combination with chlorambucil may limit its initial
use. However, this could change when data from a
Phase III trial investigating its use in combination
with FC (fludarabine and cyclophosphamide) and
bendamustine become available in 2016.
Furthermore, as Roche’s blockbuster Rituxan
faces 5EU and US patent expirations in 2013 and
2018, respectively, GlobalData anticipates that the
company’s formidable franchise management skills
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 6 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
Executive Summary
will ensure the evolution of CLL management from
Rituxan to Gazyva over the forecast period. Thus,
despite the clear demonstration of Gazyva’s
clinical superiority to Rituxan, GlobalData expects
that Gazyva will capture 20% of all first-line patient
share by 2018.
What Do the Physicians Think?
CLL experts interviewed by GlobalData were
enthusiastic about the pipeline agents, particularly
as they are keen to get away from using
chemotherapy-based regimens in the vastly elderly
CLL population. Although chemoimmunotherapy
regimens such as FCR can provide high efficacy
and long-term disease control in young or fit CLL
patients, the short and long-term toxicities
associated with the use of fludarabine are not
viewed favorably by either patients or physicians.
“Intensive chemoimmunotherapy, that’s not what
people are interested in at all. The issue is getting
away from chemotherapy.”
US Key Opinion Leader, March 2014
“You need to be minded [mindful] of the long-term
toxicities of FCR, such as myelodysplasia and
acute leukemia. There have been a percentage of
cases [involving these diseases], so imagine if you
are going to give that [FCR] to patients who have
[already] received that [FCR] twice, for example;
that could be a problem. So, I think in those
patients, probably one will try to use one of the
newer agents.”
European Key Opinion Leader, March 2014
While KOLs had favorable impressions of
Imbruvica and idelalisib, they acknowledged that,
due to the present lack of mature data, they could
not be certain of the long-term benefit provided by
these drugs. For example, these new agents have
not yet demonstrated a significant benefit in
minimal residual disease (MRD) negativity, raising
the possibility that they may not be able to induce
lengthy remissions similar to those seen with
standard FCR therapy. Thus, until mature data
suggest otherwise, or trials to compare the new
agents with FCR are conducted, KOLs expressed
hesitancy to replace FCR as the first-line treatment
of choice in young or fit CLL patients. GlobalData
thus expects that the use of Imbruvica and
idelalisib will initially be largely reserved for elderly,
17p, or relapsed/refractory patients for whom other
efficacious therapeutic options are otherwise
lacking.
“FCR will likely remain the treatment of choice for
younger, fit, ‘go-go’ patients. New agents will be
used for older patients and those [who are] unfit for
FCR. Trials [are] need[ed] to determine the role of
the new agents in unfit patients, first, and if they
work, trials [will be needed] to compare FCR with
new agents as first-line therapy in all kinds of
patients….It will take time.”
European Key Opinion Leader, February 2014
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 7 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
Executive Summary
“So, we know that if you give FCR, and you
achieve complete remission, you are within the
group of patients who are what we call MRD-
negative. Their remission is deeper; it’s greater
quality. These patients are going to do extremely
well with nothing else for periods of five to 10 years
without any further treatments. But, with the
ibrutinib-type agent, you don’t seem to get…or it’s
not clear whether you get, negative minimal
residual disease so frequently. There may be a
percentage of patients [who do get negative MRD],
but [it is] very small, and you need to treat [them]
continuously for a very long period time.”
European Key Opinion Leader, March 2014
“I would really need a trial comparing front-line
FCR and front-line FC-Gazyva, and showing that
there is really a benefit in giving FC-Gazyva. So,
unless we…have such a trial, I am not sure that
the choice of Gazyva, knowing the price and
knowing the possibility to use subcutaneous
rituximab, will soon be so high.”
European Key Opinion Leader, February 2014
While it is difficult to predict exactly what role each
of the new agents will occupy in the future CLL
treatment paradigm, GlobalData anticipates that
the management of CLL will continue to evolve
rapidly, especially as physicians are confident that
they now have the necessary tools to achieve
better responses in a wider variety of CLL patients.
“We have just been presented with a whole bunch
of fantastic new tools that we are only beginning to
learn how to use. We don’t know how to use them
in combination. There is going to be a whole lot of
unexpected findings along the way that are going
to make us change our thinking. We have got a big
project ahead of us. We have got much better
tools. Our patients are probably going to do better,
but I would be very foolish to make any real
predictions.”
US Key Opinion Leader, April 2014
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 8 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
Table of Contents
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
1 Table of Contents
1 Table of Contents ....................................................................................................................... 8
1.1 List of Tables .................................................................................................................... 12
1.2 List of Figures ................................................................................................................... 14
2 Introduction ............................................................................................................................... 16
2.1 Catalyst ............................................................................................................................. 16
2.2 Related Reports ................................................................................................................ 16
2.3 Upcoming Related Reports ............................................................................................... 17
3 Disease Overview ..................................................................................................................... 18
3.1 Etiology ............................................................................................................................. 18
3.2 Pathophysiology ................................................................................................................ 18
3.3 Staging and Prognostic Markers ....................................................................................... 19
3.3.1 Rai and Binet Staging System ....................................................................................... 19
3.3.2 Chromosomal Abnormalities and Other Prognostic Markers ......................................... 20
3.4 Symptoms ......................................................................................................................... 21
3.5 Quality of Life .................................................................................................................... 22
4 Disease Management ............................................................................................................... 23
4.1 Diagnosis .......................................................................................................................... 23
4.2 Treatment Overview .......................................................................................................... 23
4.2.1 First-Line Treatment ...................................................................................................... 25
4.2.2 Second-Line Treatment and Beyond ............................................................................. 26
4.3 Response Criteria for Evaluating the Treatment Outcome................................................. 26
5 Epidemiology ............................................................................................................................ 28
5.1 Disease Background ......................................................................................................... 28
5.2 Risk Factors and Comorbidities ........................................................................................ 29
5.3 Global Trends ................................................................................................................... 31
5.3.1 Incidence ....................................................................................................................... 31
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 9 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
Table of Contents
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
5.3.2 Survival from CLL – US and 5EU .................................................................................. 34
5.4 Forecast Methodology ....................................................................................................... 34
5.4.1 Sources Used................................................................................................................ 36
5.4.2 Sources Not Used ......................................................................................................... 38
5.4.3 Forecast Assumptions and Methods, Diagnosed Incident Cases .................................. 38
5.4.4 Forecast Assumptions and Methods, 5-Year Diagnosed Prevalent Cases .................... 40
5.4.5 Forecast Assumptions and Methods, Rai Stage at Diagnosis ........................................ 40
5.5 Epidemiological Forecast for CLL (2013–2023)................................................................. 41
5.5.1 Diagnosed Incident Cases of CLL ................................................................................. 41
5.5.2 Age-Specific Diagnosed Incident Cases of CLL ............................................................ 42
5.5.3 Sex-Specific Diagnosed Incident Cases of CLL ............................................................. 44
5.5.4 Age-Standardized Diagnosed Incidence of CLL ............................................................ 45
5.5.5 5-Year Diagnosed Prevalent Cases of CLL ................................................................... 46
5.5.6 Diagnosed Incident Cases of CLL by Rai Stage at Diagnosis ........................................ 48
5.6 Discussion ........................................................................................................................ 48
5.6.1 Epidemiological Forecast Insight ................................................................................... 48
5.6.2 Limitations of the Analysis ............................................................................................. 49
5.6.3 Strengths of the Analysis ............................................................................................... 50
6 Current Treatment Options ....................................................................................................... 51
6.1 Overview ........................................................................................................................... 51
6.2 Product Profiles – Major Brands ........................................................................................ 52
6.2.1 Rituxan/MabThera (rituximab) ....................................................................................... 52
6.2.2 Arzerra (ofatumumab) ................................................................................................... 56
6.2.3 Campath (alemtuzumab) ............................................................................................... 60
6.2.4 Treanda/Levact (bendamustine) .................................................................................... 63
6.2.5 Gazyva/Gazyvaro (obinutuzumab) ................................................................................ 66
6.2.6 Imbruvica (ibrutinib) ....................................................................................................... 69
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 10 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
Table of Contents
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
7 Unmet Needs Assessment and Oppportunity Analysis ............................................................. 75
7.1 Overview ........................................................................................................................... 75
7.2 Unmet Needs Analysis ...................................................................................................... 76
7.2.1 Unmet Need: Therapies that are tolerable for elderly, unfit patients .............................. 76
7.2.2 Unmet Need: Efficacious Therapies for High-Risk 17p Deletion Patients ...................... 77
7.2.3 Unmet Need: Safe and Efficacious Therapeutic Options for Relapsed/Refractory Patients ........................................................................................................................ 78
7.2.4 Unmet Need: Prognostic Markers to Determine the Best Treatment Strategy ............... 79
7.2.5 Unmet Need: Clinical Trials Designed to Reflect the Average CLL Patient .................... 80
7.3 Opportunity Analysis ......................................................................................................... 80
7.3.1 Opportunity: Development of Better Tolerated Therapies .............................................. 80
7.3.2 Opportunity: Development of Combination Therapy ...................................................... 81
7.3.3 Opportunity: Increasing the Cost-Effectiveness of New Therapies ................................ 81
7.3.4 Opportunity: Development of a Prognostic Index ........................................................... 82
7.3.5 Opportunity: Identification of Patients Who Could Benefit from Early Treatment ............ 83
8 R&D Strategies ......................................................................................................................... 84
8.1 Overview ........................................................................................................................... 84
8.1.1 Moving Towards a Chemotherapy-Free Future ............................................................. 84
8.1.2 Targeting the High-Risk 17p Deletion Population .......................................................... 85
8.1.3 Targeting the B-Cell Receptor Signaling Pathway in CLL .............................................. 85
8.1.4 Combination Therapy .................................................................................................... 87
8.1.5 Oral Formulations .......................................................................................................... 88
8.2 Clinical Trial Design .......................................................................................................... 89
8.2.1 Re-Assessing Treatment Outcome Criteria to Support the Development of New Agents to Treat CLL ................................................................................................................. 89
8.2.2 Evaluating CLL Clinical Trial Endpoints ......................................................................... 90
8.2.3 Selecting Suitable Comparator Arms and Combinations ............................................... 91
8.2.4 Current Clinical Trial Design .......................................................................................... 93
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 11 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
Table of Contents
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
9 Pipeline Assessment................................................................................................................. 95
9.1 Overview ........................................................................................................................... 95
9.2 Promising Drugs in Clinical Development .......................................................................... 96
9.2.1 Idelalisib (GS-1101, CAL-101) ....................................................................................... 96
9.2.2 IPI-145 ........................................................................................................................ 101
9.2.3 ABT-199 ...................................................................................................................... 104
9.3 Innovative Early-Stage Approaches ................................................................................ 108
9.3.1 CTL019 ....................................................................................................................... 109
9.3.2 Otlertuzumab (TRU-016) ............................................................................................. 110
9.3.3 Afuresertib ................................................................................................................... 111
9.3.4 GS-9973 ...................................................................................................................... 112
9.3.5 NOX-A12 ..................................................................................................................... 113
10 Pipeline Valuation Analysis ..................................................................................................... 114
10.1 Clinical Benchmark of Key Pipeline Drugs ...................................................................... 114
10.2 Commercial Benchmark of Key Pipeline Drugs ............................................................... 117
10.3 Competitive Assessment ................................................................................................. 118
10.4 Top-Line Five-Year Forecast ........................................................................................... 120
10.4.1 US ............................................................................................................................... 123
10.4.2 5EU ............................................................................................................................. 123
11 Appendix................................................................................................................................. 124
11.1 Bibliography .................................................................................................................... 124
11.2 Abbreviations .................................................................................................................. 138
11.3 Methodology ................................................................................................................... 142
11.4 Forecasting Methodology ................................................................................................ 142
11.4.1 Diagnosed CLL Patients .............................................................................................. 142
11.4.2 Percentage of Drug-Treated Patients .......................................................................... 143
11.4.3 Drugs Included in Each Therapeutic Class .................................................................. 143
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 12 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
Table of Contents
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
11.4.4 Launch and Patent Expiry Dates ................................................................................. 144
11.4.5 General Pricing Assumptions ...................................................................................... 144
11.4.6 Individual Drug Assumptions ....................................................................................... 145
11.4.7 Generic Erosion .......................................................................................................... 147
11.4.8 Pricing of Pipeline Agents............................................................................................ 147
11.5 Physicians and Specialists Included in This Study .......................................................... 148
11.6 About the Authors ........................................................................................................... 149
11.6.1 Authors........................................................................................................................ 149
11.6.2 Epidemiologist ............................................................................................................. 150
11.6.3 Global Head of Healthcare .......................................................................................... 151
11.7 About GlobalData ............................................................................................................ 152
11.8 Disclaimer ....................................................................................................................... 152
1.1 List of Tables
Table 1: Rai and Binet Staging of CLL....................................................................................................... 20
Table 2: iwCLL Symptoms of Progressive CLL .......................................................................................... 22
Table 3: Definitions of the Response to Treatment of CLL ......................................................................... 27
Table 4: CLL Clinical Stages at Diagnosis ................................................................................................. 29
Table 5: Risk Factors and Comorbidities for CLL ....................................................................................... 30
Table 6: Trends in the Age-Adjusted Incidence of CLL in the US, All Ages, 2003–2010 ............................. 32
Table 7: Trends in the Age-Adjusted Incidence of CLL (Cases per 100,000 Population) in France, All Ages,
1980–2012 .................................................................................................................................. 33
Table 8: Trends in the 5-Year Relative Survival (%) of CLL in the US and 5EU, Both Sexes, 1993–2009... 34
Table 9: Sources of Epidemiological Data Used to Forecast the CLL Diagnosed Incident and Prevalent
Cases, and the Rai Stage at Diagnosis ........................................................................................ 35
Table 10: 6MM, Diagnosed Incident Cases of CLL, Both Sexes, Ages ≥40 Years, N, 2013–2023 ................ 41
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 13 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
Table of Contents
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
Table 11: 6MM, Age-Specific Diagnosed Incident Cases of CLL, Both Sexes, N (Row %), 2013 ................. 43
Table 12: 6MM, Sex-Specific Diagnosed Incident Cases of CLL, Ages ≥40 Years, N (Row %), 2013 ........... 44
Table 13: 6MM, 5-Year Diagnosed Prevalent Cases of CLL, Both Sexes, Ages ≥40 Years, N, 2013–2023 .. 47
Table 14: Leading Treatments for CLL ........................................................................................................ 52
Table 15: Product Profile – Rituxan ............................................................................................................. 54
Table 16: Rituxan SWOT Analysis .............................................................................................................. 56
Table 17: Product Profile – Arzerra ............................................................................................................. 58
Table 18: Arzerra SWOT Analysis ............................................................................................................... 60
Table 19: Product Profile – Campath........................................................................................................... 61
Table 20: Campath SWOT Analysis ............................................................................................................ 62
Table 21: Product Profile – Treanda ............................................................................................................ 64
Table 22: Treanda SWOT Analysis ............................................................................................................. 65
Table 23: Product Profile – Gazyva ............................................................................................................. 67
Table 24: Gazyva SWOT Analysis .............................................................................................................. 69
Table 25: Product Profile – Imbruvica .......................................................................................................... 72
Table 26: Imbruvica SWOT Analysis ........................................................................................................... 74
Table 27: Overall Unmet Needs – Current Level of Attainment .................................................................... 76
Table 28: BCR Signaling Pathway Inhibitors in Clinical Development in CLL ............................................... 87
Table 29: Design of Current Phase III Trials in CLL ..................................................................................... 93
Table 30: CLL – Late-Stage Pipeline, 2014 ................................................................................................. 96
Table 31: Product Profile – Idelalisib (GS-1101, CAL-101) .......................................................................... 99
Table 32: Idelalisib SWOT Analysis........................................................................................................... 101
Table 33: Product Profile – IPI-145 ........................................................................................................... 102
Table 34: IPI-145 SWOT Analysis ............................................................................................................. 104
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 14 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
Table of Contents
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
Table 35: Product Profile – ABT-199 ......................................................................................................... 106
Table 36: ABT-199 SWOT Analysis .......................................................................................................... 108
Table 37: Early-Stage Pipeline Products in CLL ........................................................................................ 109
Table 38: Clinical Benchmark of Key Pipeline Drugs – First-Line CLL ........................................................ 115
Table 39: Clinical Benchmark of Key Pipeline Drugs – Relapsed/Refractory CLL ...................................... 116
Table 40: Commercial Benchmark of Key Pipeline Drugs .......................................................................... 117
Table 41: Top-Line Sales Forecasts ($) for CLL, 2013–2018 ..................................................................... 121
Table 42: Key Events Impacting Sales for CLL, 2013–2018 ...................................................................... 122
Table 43: CLL Market in the US and 5EU – Drivers and Barriers, 2013–2018............................................ 122
Table 44: Key Launch Dates ..................................................................................................................... 144
Table 45: Key Patent Expiries ................................................................................................................... 144
1.2 List of Figures
Figure 1: Treatment Algorithm for CLL ....................................................................................................... 24
Figure 2: 6MM, Diagnosed Incident Cases of CLL, Both Sexes, Ages ≥40 Years, N, 2013–2023 ................ 42
Figure 3: 6MM, Age-Specific Diagnosed Incident Cases of CLL, Both Sexes, N, 2013 ................................ 43
Figure 4: 6MM, Sex-Specific Diagnosed Incident Cases of CLL, Ages ≥40 Years, N, 2013 ......................... 45
Figure 5: 6MM, Age-Standardized Diagnosed Incidence of CLL (Cases per 100,000 Population), Ages ≥40
Years, by Sex, 2013 .................................................................................................................... 46
Figure 6: 6MM, 5-Year Diagnosed Prevalent Cases of CLL, Both Sexes, Ages ≥40 Years, N, 2013–2023 .. 47
Figure 7: 6MM, Diagnosed Incident Cases of CLL by Rai Stage at Diagnosis, Ages ≥40 Years, N, 2013 .... 48
Figure 8: Gazyva– Phase II and III Trials .................................................................................................... 68
Figure 9: Imbruvica – Phase II and III Trials................................................................................................ 72
Figure 10: The BCR Signaling Pathway in CLL ............................................................................................ 86
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 15 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
Table of Contents
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
Figure 11: The Evolving CLL Treatment Landscape ..................................................................................... 88
Figure 12: Idelalisib – Phase II and III Trials ................................................................................................. 97
Figure 13: IPI-145 – Phase Ib and III Trials ................................................................................................ 103
Figure 14: ABT-199 – Phase II and III Trials ............................................................................................... 106
Figure 15: Competitive Assessment of Key Marketed and Pipeline Drugs – First-Line CLL ......................... 119
Figure 16: Competitive Assessment of Key Marketed and Pipeline Drugs – Relapsed/Refractory CLL ........ 120
Figure 17: Global Sales for CLL by Region (US and 5EU), 2013–2018 ....................................................... 121
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 16 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
Introduction
2 Introduction
2.1 Catalyst
In the past decade, chronic lymphocytic leukemia (CLL) treatment has primarily relied upon
chemoimmunotherapy regimens. However, the global CLL market will welcome four new drugs
during the forecast period between 2013 to 2018 – Gazyva (obinutuzumab), Imbruvica (ibrutinib),
idelalisib, and IPI-145 – that will dramatically alter the CLL treatment landscape and challenge the
dominance of chemoimmunotherapy regimens. In particular, GlobalData expects patients with high
unmet needs, such as the elderly and relapsed/refractory patients, will have significantly improved
therapeutic options leading to rapid uptake of these drugs. In addition, the premium price these
drugs will demand coupled with a rapidly aging population will altogether drive robust growth of the
CLL market.
2.2 Related Reports
GlobalData (2014). Non-Small Cell Lung Cancer (NSCLC) – Global Drug Forecast and Market
Analysis to 2022 – Event-Driven Update, April 2014, GDHC002EPIDR.
GlobalData (2014). Pancreatic Cancer – Opportunity Analysis and Forecasts to 2017, March
2014, GDHC016POA.
GlobalData (2013). Bladder Cancer – Opportunity Analysis and Forecasts to 2017, December
2013, GDHC014POA.
GlobalData (2013). Acute Myeloid Leukemia (AML) – Opportunity Analysis and Forecasts to
2017, August 2013, GDHC003POA.
GlobalData (2013). Chronic Myeloid Leukemia (CML) – Global Drug Forecast and Market
Analysis to 2022, April 2013, GDHC103PIDR.
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 17 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
Introduction
2.3 Upcoming Related Reports
GlobalData (2014). Non-Hodgkin’s Lymphoma (NHL) – Opportunity Analysis and Forecasts to
2018.
GlobalData (2014). HER2+ Breast Cancer – Global Drug Forecast and Market Analysis to
2023.
GlobalData (2014). Renal Cell Carcinoma (RCC) – Global Drug Forecast and Market Analysis
to 2023.
GlobalData (2014). HER2- Breast Cancer – Global Drug Forecast and Market Analysis to
2023.
Chronic Lymphocytic Leukemia - Opportunity Analysis and Forecasts to 2018 152 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.
Appendix
CHRONIC LYMPHOCYTIC LEUKEMIA - OPPORTUNITY ANALYSIS AND FORECASTS TO 2018
11.7 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.
11.8 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.
Recommended