her2-positive breast cancer – global drug forecast … · her2-positive breast cancer – global...

REFERENCE CODE GDHC86PIDR | PUBLICATION DATE SEPTEMBER 2014

HER2-POSITIVE BREAST CANCER – GLOBAL DRUG FORECAST AND MARKET ANALYSIS

TO 2023

HER2-Positive Breast Cancer – Global Drug Forecast and Market Analysis to 2023 2 © GlobalData. This report is a licensed product and is not to be copied, reproduced, shared or resold in any form.

HER2-POSITIVE BREAST CANCER – GLOBAL DRUG FORECAST AND MARKET ANALYSIS TO 2023

Executive Summary

HER2-Positive Breast Cancer: Key Metrics in the Eight Major Pharmaceutical Markets, 2013–2023 2013 Epidemiology

Breast cancer incident cases 853,902

HER2-positive breast cancer incident cases 182,487

2013 Market Sales

US $2.41bn

5EU $1.99bn

Japan $126m

China $425m

Total $4.95bn

Late-Stage Pipeline Assessment

Number of drugs in Phase III profiled 2

Most Promising Late-Stage Pipeline Drugs Peak-Year Sales

Neratinib (Puma Biotechnology) $90m

Key Events (2013–2023) Level of Impact

Herceptin (trastuzumab) patent expiry in the 5EU in 2014

Launch of biosimilar trastuzumab in the 5EU in 2015

Approval of Perjeta (pertuzumab) in the adjuvant setting in 2017

Launch of neratinib in the metastatic setting in 2018

Launch of Kadcyla (ado-trastuzumab emtansine, T-DM1) in the adjuvant setting in 2019

2023 Market Sales

US $7.95bn

5EU $3.90bn

Japan $239m

China $613m

Total $12.70bn Source: GlobalData 5EU = France, Germany, Italy, Spain, and UK

The table above presents the key metrics for

human epidermal growth factor receptor type 2

(HER2)-positive breast cancer in the eight major

pharmaceutical markets (US, France, Germany,

Italy, Spain, UK, Japan, and China) during the

forecast period from 2013–2023.

HER2-Positive Breast Cancer Market to Increase by 2.5-Fold by 2023

In the 8MM in this report, GlobalData valued the

HER2-positive breast cancer market at $4.95

billion in 2013, and expects the market to increase

to $12.70 billion in 2023, at a Compound Annual

Growth Rate (CAGR) of 9.88%. The US

contributes almost half of the total market sales in

both 2013 and 2023.

The top drivers of growth in the HER2-positive

breast cancer market during the forecast period

include:

The rapid uptake of the premium-priced

biologics, Perjeta and Kadcyla, in all settings of

the disease, where their sales will increase at a

CAGR of 30.2% and 35.1%, respectively,

during the forecast period. By 2023, together,

they will capture 75% of the total HER2-

positive breast cancer market.

The launch of Perjeta and Kadcyla in early

disease in the neoadjuvant and adjuvant

settings will have the greatest impact on the

HER2-positive breast cancer therapeutics

market, with both agents capturing 77% of the

non-metastatic market by 2023.



Executive Summary

Combinations of branded therapies in both the

early-stage and metastatic settings will inflate

the annual cost of therapy (ACOT). For

instance, the ACOT for the combination of

Perjeta with Herceptin is three times that for

Herceptin alone in both adjuvant and

metastatic settings in the US.

A growing aging population and an increasing

incidence of HER2-positive breast cancer

cases across the 8MM. This is especially the

case in urban China, where over the forecast

period, the female population will increase

faster than in any other market covered in this

report, at a CAGR of 2.9%.

Major barriers to growth in the HER2-positive breast cancer market include:

The patent expiry of Herceptin in the 5EU in

2014, and in the US in 2019, will negatively

impact the market, as Herceptin sales will

decrease at a CAGR of 4.7% by 2023.

Tighter control of healthcare total expenditures

in the 5EU will be a significant hurdle for the

uptake of new premium-priced drugs,

especially when they are used in combination.

In the US, the Affordable Care Act (ACA) is

creating a new cost-conscious environment

that could impact the free-pricing system.

Inconsistent healthcare coverage across China

continues to be a barrier to growth in the

HER2-positive breast cancer market. In

addition, there is low participation in breast

screening programs in China, and there are

drug reimbursement issues as well.

The figure shown below provides the global sales

for HER2-positive breast cancer during the

forecast period.

Global Sales for HER2-Positive Breast Cancer by Region, 2013–2023

Source: GlobalData

$2,412

$425

$686

$450

$157

$270$126

$425

United States

France

Germany

Italy

Spain

United Kingdom

Japan

China

2013$4,950m

2023$12.697m

$7,944

$806

$1,262

$1,046

$307$475

$239 $613



Executive Summary

Roche Retains Its Monopoly in the HER2-Positive Breast Cancer Market

In 2013, Roche was the undeniable global leader

in the HER2-positive breast cancer market,

capturing 95% of the total HER2-targeted drug

sales. This leadership was built on the success of

Herceptin, which has been the standard of care in

all settings of HER2-positive breast cancer since

its launch in 1998. Herceptin alone accounted for

84% of the HER2-positive market in 2013. With a

looming patent expiry for Herceptin, Roche

recently launched two new anti-HER2 monoclonal

antibodies (mAbs): Perjeta in 2012, and Kadcyla in

2013. Roche’s mAbs have no real competition in

the market, and as such, these new agents are

forecast to see rapid uptake, thereby maintaining

Roche’s dominance of the market. By 2023,

GlobalData expects that Roche’s share of the

HER2-positive breast cancer market will exceed

$12 billion.

To enter this challenging market, competitors have

been focusing on the development of tyrosine

kinase inhibitors (TKIs). In 2007, GlaxoSmithKline

(GSK) launched Tykerb (lapatinib), the first HER2-

targeted TKI. Puma and Boehringer Ingelheim are

currently investigating TKIs for breast cancer;

however, the role for TKIs remains small, as

Tykerb accounted for less than 5% of the HER2-

positive market in 2013. Indeed, the role of TKIs in

early disease appears very uncertain. GlobalData

foresees that TKIs will only be used in later lines of

therapy, after the use of Roche’s mAbs. By the end

of the forecast period in 2023, GlobalData

anticipates that the HER2-positive TKI market will

have decreased to $198m, from $212m in 2013.

Ultimately, GlobalData believes that Roche’s

monopoly of this market will only be challenged by

companies with innovative product portfolios, such

as Novartis, and Pfizer.

The figure shown below provides an analysis of the

company portfolio gap in HER2-positive breast

cancer during the forecast period.

Company Portfolio Gap Analysis in HER2-Positive Breast Cancer, 2013–2023

Source: GlobalData

Strength of PipelineLow

Hig

hLo

wS

treng

th o

f Mar

kete

d P

rodu

cts

High

Current and Future Players

Future Players

Current Players



Executive Summary

Kadcyla Will Experience Strong Uptake Across the 8MM

Since launching for use in the second-line

metastatic breast cancer setting in February 2013,

Roche’s Kadcyla has been rapidly adopted in the

US. In 2013, Kadcyla captured 10% of the US

market and 5% of the US, 5EU, and Japan. In

comparison, only 7% of patients in these markets

in which Perjeta was launched received Perjeta in

combination with Herceptin in the first-line setting,

despite Perjeta having been launched six months

before Kadcyla. In fact, key opinion leaders (KOLs)

and global prescribers interviewed by GlobalData

praised the high efficacy and low side effect profile

of Kadcyla, which is expected to result in its

continued strong uptake across the 8MM. With

expected approval in the first-line setting in 2017,

and as an adjuvant therapy in 2019, GlobalData

forecasts Kadcyla to become the leader in the

HER2-positive market, capturing 38% of the total

market by 2023.

Non-Metastatic Breast Cancer Represents the Largest Market for HER2-Targeting Agents

In 2013, the combined sales of anti-HER2 agents

used in the neoadjuvant and adjuvant treatment of

early-stage (non-metastatic) breast cancer

represented 55% of the total market. The use of

Herceptin is particularly strong in the adjuvant

setting, where its sales contributed to 99% of the

total adjuvant market, and 49% of total Herceptin

sales, in 2013. During the forecast period,

GlobalData expects the adjuvant and neoadjuvant

settings to remain the largest markets, and

forecasts their sales to reach $8.60 billion in 2023,

representing 67% of the total HER2-positive

market. This increase in market size will be driven

primarily by the uptake of premium-priced

therapies, such as Perjeta, which was the first drug

to receive approval in the neoadjuvant setting in

the US in 2013.

The dynamism of the adjuvant and neoadjuvant

markets has prompted many companies to try to

position their products in these settings, especially

since the early lines of therapy for metastatic

disease are considered to be inaccessible due to

Roche’s monopoly in this area. TKIs were of

particular interest, since they offer greater

convenience than mAbs, but the negative results

for Tykerb in the adjuvant setting, which were

released in early 2014, showed that TKIs may not

be a good fit for this setting. Generally, TKIs have

more side effects, with little efficacy benefit,

compared with antibodies. Therefore, GlobalData

believes that the adjuvant and neoadjuvant

settings will remain an exclusive market for anti-

HER2 mAbs, hence constituting the most lucrative

opportunity for biosimilar developments. In 2023,

GlobalData expects the biosimilar market for

trastuzumab to be worth $962m in 8MM, with 65%

of sales being in the neoadjuvant and adjuvant

settings.



Executive Summary

Better Treatment for Brain Metastases Remains the Most Pressing Unmet Need

Although the efficacy of HER2-targeted therapies

substantially improves the life expectancy of

patients with HER2-positive disease, by nature,

HER2-positive breast cancer is still a more

aggressive form of the disease, with a poorer

prognosis and worse outcomes than for patients

with HER2-negative (and hormone receptor [HR]-

positive) disease. Two unmet needs are of high

importance to increase survival in HER2-positive

disease:

The effective treatment of central nervous

system (CNS) metastases

The treatment of disease that has become

resistant to HER2-targeting therapies

HER2-targeting mAbs have failed to deliver

benefits to patients with brain metastases, because

they cannot pass the blood-brain barrier. TKIs,

such as Tykerb or neratinib, may be effective here;

however, resistance to kinase inhibitors is

common, so innovative therapies to treat TKI-

resistant HER2-positive disease will also be

required. The agents in early-stage development

that target phosphoinositide 3-kinase (PI3K), such

as NVP-BYL719 and the cyclin-dependent kinase

4/6 (CDK 4/6) inhibitor, palbociclib, have both been

suggested for use in the treatment of anti-HER2-

resistant breast cancer. With impressive results in

the HER2-negative setting, as well as some

evidence of blood-brain barrier penetration, these

agents also have the possibility of addressing the

unmet needs that plague the HER2-positive

market.

Future Breast Cancer Therapies Will Unite the HER2-Positive and HER2- Negative Markets

The agents in the most advanced stages of

development for HER2-positive breast cancer are

the TKIs — namely, Boehringer Ingelheim’s (BIs)

Gilotrif (afatinib) and Puma’s neratinib. However,

recent study results show that TKIs may not

demonstrate a great benefit over the existing

therapies. GlobalData foresees that TKIs will be

used in these scenarios: almost exclusively in later

lines of therapy; after the failure of anti-HER2

therapies in the earlier stages of metastatic

disease; or for patients with known brain

metastases. Puma is positioning neratinib for use

as a later line of therapy, and in this setting

(second-line metastatic and beyond), GlobalData

forecasts neratinib to generate $128m in sales by

2023.

A very limited number of agents are being

developed specifically for HER2-positive breast

cancer. For example, Array’s ARRY-380 (ONT-

380) is another TKI that is currently in Phase I/II for

HER2-positive disease, while Galena is developing

NeuVax (nelipepimut-S), a vaccine that is also

being investigated in HER2-negative disease. In

fact, GlobalData believes that the most promising

agents for HER2-positive disease are being

developed primarily for HER2-negative disease. In

particular, KOLs have expressed interest in PI3K



Executive Summary

inhibitors, such as Novartis’s BYL-719, as well as

in CDK 4/6 inhibitors, such as Pfizer’s palbociclib

and Novartis’s LEE011, in the treatment of HER2-

positive disease. Other drugs in the early phases

of development include Daiichi Sankyo’s

patritumab (U3-1287), which is an anti-HER3 mAb,

and Syntha’s ganetespib (STA-9090), which is a

heat shock protein 90 (HSP90) inhibitor. However,

the clinical relevance of these agents still remains

to be established.

The HER2-positive market has become very

mature since the launch of anti-HER2 antibodies.

For agents to be successful, the strategy may not

be to target HER2 specifically, but rather, to target

a separate pathway that is applicable to both

HER2-positive and -negative disease, thus unifying

the breast cancer market.

“For HER2-negative disease, [there] is much

easier uptake [of drugs], so that is why they went

there [first]. But obviously, those kinds of drugs

could be of high interest in HER2-positive disease,

too.”

OUS Key Opinion Leader, April 2014

“…drugs like palbociclib will be very interesting in

HER2-positive disease, and some of them do

cross the blood-brain barrier, so…those might be

interesting approaches.”

US Key Opinion Leader, January 2014

The figure shown below provides a competitive

assessment of the most promising agents for

HER2-positive breast cancer during the forecast

period.

Competitive Assessment of Most Promising Agents for HER2-Positive Breast Cancer, 2013–2023

Source: GlobalData

Clinical AttributesLow

Hig

hLo

wC

omm

erci

al A

ttrib

utes

High

Puma’sneratinib

HER2-targeting agent

Other mechanisms of action

Galena’sNeuVax

Array’sARRY-380

Syntha’sganetespib

Daiichi Sankyo’spatritumab

Novartis’NVP-BYL719

Novartis’LEE011

Pfizer’spalbociclib



Executive Summary

What Do Physicians Think?

KOLs praised the efficacy of Kadcyla for metastatic

disease, and are already anticipating its use in

earlier settings.

“The effectiveness with the lack of toxicity is one of

the big attractions of T-DM1 [Kadcyla].”


“I am a big believer in TDM-1. I did lots of those

first trials with TDM-1, and I think it’s a great drug.

And so, we are very hopeful that it’s going to have

positive results in the different adjuvant trials that

are underway.”


“We are hopeful that HER2-positive disease will be

essentially cured in the next decade, or shorter, by

the new agents that we have, that all clearly

showed a dramatic benefit in patients who had

received prior trastuzumab in the case of Kadcyla,

and in those who hadn’t [been treated with prior

trastuzumab] in the case of Perjeta. I mean, there

was clearly an improved survival. So, that suggests

that by adding those agents in some form in the

early-stage setting, that we will cure more patients

with HER2-positive disease.”


“If [Kadcyla] turned out to be an active agent in the

early-stage setting, that’s where it will get used. I

mean, ultimately, there is not going to be a desire

to hold back on drugs — [that is,] to use better

drugs later. We are going to want to use our best

drugs up front. If T-DM1 is better, and we can use

T-DM1 up front and have a better result in terms of

efficacy, and have a lower toxicity, then that’s what

will be used.”

US Key Opinion Leader, December 2013

KOLs still believe there is room for TKIs, especially

after disease progression following the use of anti-

HER2 mAbs. Neratinib, in particular, is a TKI under

development that they are looking forward to using

in the metastatic setting.

“What I tell people is, at some point, you should be

using a lapatinib combination, either with Herceptin

or with Xeloda [(capecitabine)], and then you

should be using whatever other chemotherapies

with Herceptin that you have still left — eribulin,

navelbine, gemcitabine — and I don’t think the

order matters.”




Executive Summary

“In my opinion, it [Tykerb] has always been a very

promising drug, but the promise…has never been

held in the clinic, probably because of scheduling,

which doesn’t allow the full potential of anti-tumor

activity because you have to stop at a certain point

because of unacceptable toxicity. The same is for

neratinib or afatinib; probably playing with the

schedule and ensuring optimal exposure of the

tumor to optimal saturation of receptors may really

reveal additional properties of these drugs in the

treatment of trastuzumab-, or antibody-, in general,

refractory HER2-positive tumors.”


“[Neratinib is] such a potent oral tyrosine kinase

inhibitor [that], maybe instead of pitching

themselves against Herceptin, they could look at

how they are going to work in patients who don’t

respond, or who have higher-risk disease, or

afterwards, etcetera.”


“[Neratinib is a] drug that has a very impressive

anti-tumor activity, very impressive. I remember the

Phase II study in patients [who were] never treated

before with anti-tumor agents, that, as a single

agent it, gave a 50% response rate, which is quite

remarkable.”


“The real difficulty is that the market has moved on

so much from when the trials [for neratinib and

Gilotrif] have been done, and one assumes these

drugs are going to be expensive, with a lot of

toxicity, and without a clear data set to support

them, because everyone has moved on to giving

totally different treatment. I think it’s going to be

much harder to get those in.”


Effective therapies for the treatment of brain

metastases remain the biggest unmet need, and

KOLs are interested to see how cyclin-dependant

kinase inhibitors, which are currently in

development for HER2-negative disease, can

deliver in this setting.

“…HER2-positive patients very frequently get brain

metastases….Radiation is a good treatment, but it

doesn’t last forever, so progression in the brain

after radiation is a real problem. We do not have

any good treatments for that; that’s an unmet

medical need.”




Executive Summary

“Another class of drugs which has activity in HER2-

positive disease, but is being pursued in ER

[estrogen-receptor]-positive disease, of course, are

CDK 4/6 inhibitors, and those are quite

interesting….They have the potential of crossing

the blood-brain barrier, and are highly effective in

ER-positive disease, and I’m hopeful [that we] are

going to really change the course of patients who

have ER-positive breast cancer.”



Table of Contents


1 Table of Contents

1 Table of Contents ..................................................................................................................... 11

1.1 List of Tables .................................................................................................................... 18

1.2 List of Figures ................................................................................................................... 23

2 Introduction ............................................................................................................................... 26

2.1 Catalyst ............................................................................................................................. 26

2.2 Related Reports ................................................................................................................ 26

2.3 Upcoming Related Reports ............................................................................................... 27

3 Disease Overview ..................................................................................................................... 28

3.1 Etiology and Pathophysiology ........................................................................................... 28

3.1.1 Etiology ......................................................................................................................... 28

3.1.2 Pathophysiology ............................................................................................................ 28

3.2 Basic Breast Anatomy ....................................................................................................... 30

3.3 Breast Cancer Staging ...................................................................................................... 31

3.4 Prognosis .......................................................................................................................... 32

3.5 Quality of Life .................................................................................................................... 33

3.6 Symptoms ......................................................................................................................... 35

4 Epidemiology ............................................................................................................................ 36

4.1 Disease Background ......................................................................................................... 36

4.2 Risk Factors and Comorbidities ........................................................................................ 37

4.2.1 A family history of breast cancer and BRCA1/2 gene mutations significantly increase the breast cancer risk ......................................................................................................... 38

4.2.2 Reproductive hormonal factors influence the risk of breast cancer ................................ 39

4.2.3 Modifiable lifestyle-related factors increase the risk of mortality in breast cancer patients ..................................................................................................................................... 41

4.2.4 Screening programs have been shown to reduce breast cancer mortality, although the benefits need to be carefully weighed against the risks ................................................ 43

4.3 Global Trends ................................................................................................................... 45


Table of Contents


4.3.1 Incidence ....................................................................................................................... 45

4.3.2 Prevalence and Survival ................................................................................................ 51

4.4 Forecast Methodology ....................................................................................................... 55

4.4.1 Sources Used................................................................................................................ 56

4.4.2 Sources Not Used ......................................................................................................... 61

4.4.3 Forecast Assumptions and Methods ............................................................................. 61

4.5 Epidemiological Forecast for Breast Cancer (2013–2023) – Diagnosed Incident Cases ... 65

4.5.1 Diagnosed Incident Cases of Breast Cancer ................................................................. 65

4.5.2 Diagnosed Incident Cases of Breast Cancer by Age ..................................................... 67

4.5.3 Diagnosed Incident Cases of Breast Cancer by Menopausal Status ............................. 69

4.5.4 Diagnosed Incident Cases of Breast Cancer Segmented by Stage at Diagnosis ........... 71

4.5.5 Age-Standardized Diagnosed Incidence Rate of Breast Cancer .................................... 72

4.6 Epidemiological Forecast for Breast Cancer (2013–2023) — Diagnosed Prevalent Cases73

4.6.1 Five-Year Diagnosed Prevalent Cases of Breast Cancer .............................................. 73

4.6.2 Five-Year Diagnosed Prevalent Cases by Menopausal Status ...................................... 75

4.6.3 Five-Year Diagnosed Prevalent Cases by Hormone Receptor Subtypes ....................... 76

4.7 Discussion ........................................................................................................................ 78

4.7.1 Epidemiological Forecast Insight ................................................................................... 78

4.7.2 Limitations of the Analysis ............................................................................................. 80

4.7.3 Strengths of the Analysis ............................................................................................... 81

5 Disease Management ............................................................................................................... 83

5.1 Treatment Overview .......................................................................................................... 83

5.1.1 Treatment of Early-Stage Breast Cancer (Stage 0 to Stage IB) ..................................... 83

5.1.2 Treatment of Locally-Advanced and Regional Breast Cancer (Stage IB to IIIA) ............. 84

5.1.3 Treatment of Metastatic HER2-Positive Breast Cancer (Stage IV) ................................ 87

5.2 US..................................................................................................................................... 90

5.2.1 Diagnosis ...................................................................................................................... 90


Table of Contents


5.2.2 Clinical Practice ............................................................................................................. 90

5.3 France .............................................................................................................................. 93

5.3.1 Diagnosis ...................................................................................................................... 93


5.4 Germany ........................................................................................................................... 96

5.4.1 Diagnosis ...................................................................................................................... 96


5.5 Italy ................................................................................................................................... 99

5.5.1 Diagnosis ...................................................................................................................... 99


5.6 Spain .............................................................................................................................. 102

5.6.1 Diagnosis .................................................................................................................... 102

5.6.2 Clinical Practice ........................................................................................................... 103

5.7 UK................................................................................................................................... 104

5.7.1 Diagnosis .................................................................................................................... 104


5.8 Japan .............................................................................................................................. 108

5.8.1 Diagnosis .................................................................................................................... 108


5.9 China .............................................................................................................................. 109

5.9.1 Diagnosis .................................................................................................................... 109


6 Competitive Assessment ........................................................................................................ 112

6.1 Overview ......................................................................................................................... 112

6.2 Product Profiles – HER2-Targeted Therapies ................................................................. 113

6.2.1 Herceptin (trastuzumab) .............................................................................................. 113

6.2.2 Tykerb (lapatinib) ........................................................................................................ 120


Table of Contents


6.2.3 Perjeta (pertuzumab) ................................................................................................... 125

6.2.4 Kadcyla (ado-trastuzumab emtansine, T-DM1) ........................................................... 130

6.3 Product Profiles – General Targeted Therapies .............................................................. 134

6.3.1 Afinitor (everolimus) .................................................................................................... 134

6.3.2 Xeloda (capecitabine) .................................................................................................. 138

6.3.3 Avastin (bevacizumab) ................................................................................................ 141

6.3.4 Halaven (eribulin mesylate) ......................................................................................... 144

6.3.5 Abraxane (nab-paclitaxel)............................................................................................ 148

6.3.6 Ixempra (ixabepilone) .................................................................................................. 151

6.4 Hormonal Agents ............................................................................................................ 155

6.4.1 Tamoxifen ................................................................................................................... 155

6.4.2 Faslodex (fulvestrant) .................................................................................................. 155

6.4.3 Aromatase Inhibitors ................................................................................................... 156

7 Unmet Need and Opportunity ................................................................................................. 158

7.1 Overview ......................................................................................................................... 158

7.2 Brain Metastases ............................................................................................................ 159

7.2.1 Unmet Need ................................................................................................................ 159

7.2.2 Gap Analysis ............................................................................................................... 159

7.2.3 Opportunity ................................................................................................................. 161

7.3 Resistance to HER2-Targeting Therapies ....................................................................... 161

7.3.1 Unmet Need ................................................................................................................ 161

7.3.2 Gap Analysis ............................................................................................................... 162

7.3.3 Opportunity ................................................................................................................. 163

8 Pipeline Assessment............................................................................................................... 165

8.1 Overview ......................................................................................................................... 165

8.2 Promising Drugs in Clinical Development ........................................................................ 166

8.2.1 Gilotrif (afatinib) ........................................................................................................... 166


Table of Contents


8.2.2 Neratinib ...................................................................................................................... 171

8.3 Promising Drugs in Early-Stage Development................................................................. 175

8.3.1 Palbociclib ................................................................................................................... 177

8.3.2 NeuVax (nelipepimut-S) .............................................................................................. 181

8.3.3 Patritumab ................................................................................................................... 185

8.3.4 Ganetespib .................................................................................................................. 188

8.3.5 ARRY-380 (ONT-380) ................................................................................................. 191

8.3.6 NVP-BYL719 ............................................................................................................... 194

8.4 Biosimilars ...................................................................................................................... 196

9 Current and Future Players ..................................................................................................... 198

9.1 Overview ......................................................................................................................... 198

9.2 Trends in Corporate Strategy .......................................................................................... 201

9.3 Company Profiles ............................................................................................................ 203

9.3.1 Roche/Genentech ....................................................................................................... 203

9.3.2 GlaxoSmithKline .......................................................................................................... 205

9.3.3 Boehringer Ingelheim .................................................................................................. 207

9.3.4 Novartis ....................................................................................................................... 208

9.3.5 Pfizer ........................................................................................................................... 211

10 Market Outlook ....................................................................................................................... 214

10.1 Global Markets ................................................................................................................ 214

10.1.1 Forecast ...................................................................................................................... 214

10.1.2 Drivers and Barriers – Global Issues ........................................................................... 219

10.2 United States .................................................................................................................. 222

10.2.1 Forecast ...................................................................................................................... 222

10.2.2 Key Events .................................................................................................................. 225

10.2.3 Drivers and Barriers .................................................................................................... 225

10.3 France ............................................................................................................................ 228


Table of Contents


10.3.1 Forecast ...................................................................................................................... 228

10.3.2 Key Events .................................................................................................................. 231


10.4 Germany ......................................................................................................................... 233

10.4.1 Forecast ...................................................................................................................... 233

10.4.2 Key Events .................................................................................................................. 236


10.5 Italy ................................................................................................................................. 238

10.5.1 Forecast ...................................................................................................................... 238

10.5.2 Key Events .................................................................................................................. 241


10.6 Spain .............................................................................................................................. 243

10.6.1 Forecast ...................................................................................................................... 243

10.6.2 Key Events .................................................................................................................. 246


10.7 United Kingdom .............................................................................................................. 248

10.7.1 Forecast ...................................................................................................................... 248

10.7.2 Key Events .................................................................................................................. 251


10.8 Japan .............................................................................................................................. 254

10.8.1 Forecast ...................................................................................................................... 254

10.8.2 Key Events .................................................................................................................. 257


10.9 China .............................................................................................................................. 259

10.9.1 Forecast ...................................................................................................................... 259

10.9.2 Key Events .................................................................................................................. 262



Table of Contents


11 Appendix................................................................................................................................. 265

11.1 Bibliography .................................................................................................................... 265

11.2 Abbreviations .................................................................................................................. 295

11.3 Methodology ................................................................................................................... 303

11.4 Forecasting Methodology ................................................................................................ 303

11.4.1 Diagnosed HER2-Positive Breast Cancer Patients ...................................................... 303

11.4.2 Percent Drug-Treated Patients .................................................................................... 304

11.4.3 Drugs Included in Each Therapeutic Class .................................................................. 304

11.4.4 Launch and Patent Expiry Dates ................................................................................. 305

11.4.5 General Pricing Assumptions ...................................................................................... 306

11.4.6 Individual Drug Assumptions ....................................................................................... 307

11.4.7 Generic Erosion .......................................................................................................... 316

11.4.8 Pricing of Pipeline Agents............................................................................................ 316

11.5 Primary Research – KOLs Interviewed for this Report .................................................... 318

11.6 Primary Research – Prescriber Survey ........................................................................... 320

11.7 About the Authors ........................................................................................................... 321

11.7.1 Analyst ........................................................................................................................ 321

11.7.2 Therapy Area Director ................................................................................................. 321

11.7.3 Epidemiologist ............................................................................................................. 322

11.7.4 Acting Director of Epidemiology................................................................................... 322

11.7.5 Global Head of Healthcare .......................................................................................... 323

11.8 About GlobalData ............................................................................................................ 324

11.9 Disclaimer ....................................................................................................................... 324


Table of Contents


1.1 List of Tables

Table 1: AJCC Stage Definitions for Breast Cancer ................................................................................... 32

Table 2: Prognosis for Breast Cancer in the US ........................................................................................ 33

Table 3: Selected Major Risk Factors and Comorbidities for Breast Cancer ............................................... 38

Table 4: Breast Cancer Mortality Attributable to Lifestyle-Related Risk Factors.......................................... 42

Table 5: 8MM, Current Status and Plans of Large-Scale Breast Cancer Screening Programs.................... 44

Table 6: 8MM, Relative Survival Rate for Breast Cancer, All Ages*, Women, %, 1991–2004** .................. 51

Table 7: Conversion of Common Staging Systems for Breast Cancer Used in the Forecast ....................... 55

Table 8: 8MM, Sources of the Breast Cancer Diagnosed Incidence Data Used in the Epidemiological

Forecast ...................................................................................................................................... 56

Table 9: 8MM, Diagnosed Incident Cases of Breast Cancer, Ages ≥20 Years, Women, N, 2013–2023 ...... 66

Table 10: 8MM, Diagnosed Incident Cases of Breast Cancer by Age, Women, N (Row %), 2013 ................ 68

Table 11: 8MM, Diagnosed Incident Cases of Breast Cancer by Menopausal Status, Ages ≥20 Years,

Women, N (Row %), 2013 ........................................................................................................... 70

Table 12: 8MM, Diagnosed Incident Cases of Breast Cancer by Stage at Diagnosis, Ages ≥20 Years,

Women, N, 2013 ......................................................................................................................... 71

Table 13: 8MM, Five-Year Diagnosed Prevalent Cases of Breast Cancer, Ages ≥20 Years, Women, N,

2013–2023 .................................................................................................................................. 74

Table 14: 8MM, Five-Year Diagnosed Prevalent Cases of Breast Cancer by Hormone Receptor Subtypes,

Ages ≥20 Years, Women, N, 2013 ............................................................................................... 77

Table 15: Treatment Guidelines for HER2-Positive Breast Cancer .............................................................. 89

Table 16: Product Profile – Herceptin ........................................................................................................ 115

Table 17: Clinical Studies for Herceptin in the Adjuvant Setting ................................................................. 117

Table 18: Herceptin SWOT Analysis, 2013................................................................................................ 119

Table 19: Global Sales Forecast ($m) for Herceptin, 2013–2023 ............................................................... 120

Table 20: Product Profile – Tykerb ............................................................................................................ 122


Table of Contents


Table 21: Tykerb SWOT Analysis, 2013 .................................................................................................... 124

Table 22: Global Sales Forecast ($m) for Tykerb, 2013–2023 ................................................................... 125

Table 23: Product Profile – Perjeta ............................................................................................................ 127

Table 24: Perjeta SWOT Analysis, 2013 ................................................................................................... 129

Table 25: Global Sales Forecast ($m) for Perjeta, 2013–2023 ................................................................... 129

Table 26: Product Profile – Kadcyla .......................................................................................................... 131

Table 27: Kadcyla SWOT Analysis, 2013 .................................................................................................. 133

Table 28: Global Sales Forecast ($m) for Kadcyla, 2013–2023 ................................................................. 134

Table 29: Product Profile – Afinitor ............................................................................................................ 136

Table 30: Afinitor SWOT Analysis, 2013.................................................................................................... 137

Table 31: Product Profile – Xeloda ............................................................................................................ 139

Table 32: Xeloda SWOT Analysis, 2013.................................................................................................... 141

Table 33: Product Profile – Avastin ........................................................................................................... 142

Table 34: Summary of Avastin Phase III Clinical Trials in Metastatic Breast Cancer .................................. 143

Table 35: Avastin SWOT Analysis, 2013 ................................................................................................... 144

Table 36: Product Profile – Halaven .......................................................................................................... 145

Table 37: Halaven SWOT Analysis, 2013 .................................................................................................. 147

Table 38: Global Sales Forecast ($m) for Halaven, 2013–2023 ................................................................. 148

Table 39: Product Profile – Abraxane ........................................................................................................ 149

Table 40: Abraxane SWOT Analysis, 2013................................................................................................ 150

Table 41: Global Sales Forecast ($m) for Abraxane, 2013–2023 ............................................................... 151

Table 42: Product Profile – Ixempra .......................................................................................................... 152

Table 43: Ixempra SWOT Analysis, 2013 .................................................................................................. 154

Table 44: Global Sales Forecast ($m) for Ixempra, 2013–2023 ................................................................. 154


Table of Contents


Table 45: Summary of Minor Therapeutic Classes Used to Treat HER-2 positive breast cancer, 2013....... 157

Table 46: Unmet Need and Opportunity in HER2-Positive Breast Cancer .................................................. 158

Table 47: Product Profile – Gilotrif ............................................................................................................. 168

Table 48: Gilotrif SWOT Analysis, 2014 .................................................................................................... 170

Table 49: Product Profile – Neratinib ......................................................................................................... 172

Table 50: Neratinib SWOT Analysis, 2013 ................................................................................................ 175

Table 51: Global Sales Forecast ($m) for Neratinib, 2013–2023 ................................................................ 175

Table 52: Comparison of Therapeutic Classes in Development for HER2-Positive/HER2-Negative Breast

Cancer, 2014 ............................................................................................................................ 176

Table 53: HER2-Positive Breast Cancer – Early-Phase Pipeline, 2014 ...................................................... 177

Table 54: Product Profile – Palbociclib ...................................................................................................... 179

Table 55: Palbociclib SWOT Analysis, 2014 .............................................................................................. 181

Table 56: Product Profile – NeuVax .......................................................................................................... 183

Table 57: NeuVax SWOT Analysis, 2014 .................................................................................................. 185

Table 58: Product Profile – Patritumab ...................................................................................................... 186

Table 59: Patritumab SWOT Analysis, 2014.............................................................................................. 188

Table 60: Product Profile – Ganetespib ..................................................................................................... 189

Table 61: Ganetespib SWOT Analysis, 2014 ............................................................................................. 191

Table 62: Product Profile – ARRY-380 ...................................................................................................... 192

Table 63: ARRY-380 SWOT Analysis, 2014 .............................................................................................. 193

Table 64: Product Profile – NVP-BYL719 .................................................................................................. 194

Table 65: NVP-BYL719 SWOT Analysis, 2014 .......................................................................................... 195

Table 66: Trastuzumab Biosimilars, 2014 .................................................................................................. 197

Table 67: Key Companies in the HER2-Positive Breast Cancer Market in the 8MM, 2013–2023 ................ 199

Table 68: Roche’s HER2-Positive Breast Cancer Portfolio Assessment, 2014 ........................................... 204


Table of Contents


Table 69: Roche SWOT Analysis, 2014 .................................................................................................... 205

Table 70: GSK’s HER2-Positive Breast Cancer Portfolio Assessment, 2014.............................................. 206

Table 71: GSK SWOT Analysis, 2014 ....................................................................................................... 207

Table 72: BI’s HER2-Positive Breast Cancer Portfolio Assessment, 2014 .................................................. 208

Table 73: BI SWOT Analysis, 2014 ........................................................................................................... 208

Table 74: Novartis’ HER2-Positive Breast Cancer Portfolio Assessment, 2014 .......................................... 210

Table 75: Novartis SWOT Analysis, 2014 .................................................................................................. 210

Table 76: Pfizer’s HER2-Positive Breast Cancer Portfolio Assessment, 2014 ............................................ 212

Table 77: Pfizer SWOT Analysis, 2014 ..................................................................................................... 213

Table 78: Global Sales Forecast ($m) for HER2-Positive Breast Cancer, 2013–2023 ................................ 216

Table 79: Global HER2-Positive Breast Cancer Market – Drivers and Barriers, 2013–2023 ....................... 219

Table 80: Sales Forecast ($m) for HER2-Positive Breast Cancer in the US, 2013–2023 ............................ 223

Table 81: Key Events Impacting Sales for HER2-Positive Breast Cancer in the US, 2013–2023 ................ 225

Table 82: US HER2-Positive Breast Cancer Market – Drivers and Barriers, 2013–2023 ............................ 225

Table 83: Sales Forecast ($m) for HER2-Positive Breast Cancer in France, 2013–2023 ............................ 229

Table 84: Key Events Impacting Sales for HER2-Positive Breast Cancer in France, 2013–2023 ................ 231

Table 85: French HER2-Positive Breast Cancer Market – Drivers and Barriers, 2013–2023 ...................... 231

Table 86: Sales Forecast ($m) for HER2-Positive Breast Cancer in Germany, 2013–2023 ........................ 234

Table 87: Key Events Impacting Sales for HER2-Positive Breast Cancer in Germany, 2013–2023 ............ 236

Table 88: German HER2-Positive Breast Cancer Market – Drivers and Barriers, 2013–2023 .................... 236

Table 89: Sales Forecast ($m) for HER2-Positive Breast Cancer in Italy, 2013–2023 ................................ 239

Table 90: Key Events Impacting Sales for HER2-Positive Breast Cancer in Italy, 2013–2023 .................... 241

Table 91: Italian HER2-Positive Breast Cancer Market – Drivers and Barriers, 2013–2023 ........................ 241

Table 92: Sales Forecast ($m) for HER2-Positive Breast Cancer in Spain, 2013–2023.............................. 244


Table of Contents


Table 93: Key Events Impacting Sales for HER2-Positive Breast Cancer in Spain, 2013–2023.................. 246

Table 94: Spanish HER2-Positive Breast Cancer Market – Drivers and Barriers, 2013–2023 .................... 246

Table 95: Sales Forecast ($m) for HER2-Positive Breast Cancer in the UK, 2013–2023 ............................ 249

Table 96: Key Events Impacting Sales for HER2-Positive Breast Cancer in the UK, 2013–2023 ................ 251

Table 97: UK HER2-Positive Breast Cancer Market – Drivers and Barriers, 2013–2023 ............................ 251

Table 98: Sales Forecast ($m) for HER2-Positive Breast Cancer in Japan, 2013–2023 ............................. 255

Table 99: Key Events Impacting Sales for HER2-Positive Breast Cancer in Japan, 2013–2023 ................. 257

Table 100: Japanese HER2-Positive Breast Cancer Market – Drivers and Barriers, 2013–2023 .................. 257

Table 101: Sales Forecast ($m) for HER2-Positive Breast Cancer in China, 2013–2023 ............................. 260

Table 102: Key Events Impacting Sales for HER2-Positive Breast Cancer in China, 2013–2023 ................. 262

Table 103: Chinese HER2-Positive Breast Cancer Market – Drivers and Barriers, 2013–2023 .................... 262

Table 104: HER2-Positive Breast Cancer Incidence, 2013–2023 ................................................................ 304

Table 105: HER2-Positive Breast Cancer Drugs, Key Launch Dates ........................................................... 305

Table 106: HER2-Positive Breast Cancer Drugs, Key Patent Expiries ......................................................... 306

Table 107: Average Body Weight and Surface Area Across the 8MM .......................................................... 307

Table 108: Average Annual Cost of Therapy ($) – Herceptin, Adjuvant........................................................ 309

Table 109: Average Annual Cost of Therapy ($) – Subcutaneous Herceptin, Adjuvant ................................ 310

Table 110: Average Annual Cost of Therapy ($) – Perjeta, First Line ........................................................... 311

Table 111: Average Annual Cost of Therapy ($) – Tykerb, First Line ........................................................... 312

Table 112: Average Annual Cost of Therapy ($) – Kadcyla, Second Line .................................................... 313

Table 113: Average Annual Cost of Therapy ($)– Halaven, Fourth Line....................................................... 313

Table 114: Average Annual Cost of Therapy ($) – Abraxane, Fourth Line ................................................... 314

Table 115: Average Annual Cost of therapy ($) – Ixempra, Fourth Line ....................................................... 315

Table 116: Average Annual Cost of Therapy ($) – Neratinib, Third Line....................................................... 317


Table of Contents


Table 117: Physicians Surveyed by Country ............................................................................................... 320

1.2 List of Figures

Figure 1: Basic Breast Anatomy, Including Key Lymph Nodes .................................................................... 30

Figure 2: 8MM, Age-Standardized Incidence Rate of Breast Cancer, Ages ≥15 Years, Women, Cases per

100,000 Population, 2008 ............................................................................................................ 45

Figure 3: 8MM, Incidence Rate of Breast Cancer, Ages ≥15 Years, Women, Rate per 100,000 Population,

2008............................................................................................................................................ 46

Figure 4: US, Incidence Rate of Breast Cancer, All Ages, Women, Cases per 100,000 Population, 1975–

2009............................................................................................................................................ 47

Figure 5: 5EU, Incidence Rate of Breast Cancer, Ages ≥15 Years, Women, Cases per 100,000 Population,

1975–2010 .................................................................................................................................. 49

Figure 6: Japan, Incidence Rate of Breast Cancer, All Ages, Women, Cases per 100,000 Population, 2003–

2008............................................................................................................................................ 50

Figure 7: 8MM, Relative Survival Rate for Breast Cancer, All Ages*, Women, %, 1991–2004** .................. 52

Figure 8: 8MM, Diagnosed Incident Cases of Breast Cancer, Ages ≥20 Years, Women, N, 2013–2023 ...... 66

Figure 9: 8MM, Diagnosed Incident Cases of Breast Cancer, by Age, Women, N, 2013 ............................. 69

Figure 10: 8MM, Diagnosed Incident Cases of Breast Cancer by Menopausal Status, Ages ≥20 Years,

Women, N, 2013 ......................................................................................................................... 70

Figure 11: 8MM, Diagnosed Incident Cases of Breast Cancer by Stage at Diagnosis, Ages ≥20 Years,

Women, N, 2013 ......................................................................................................................... 72

Figure 12: 8MM, Age-Standardized Diagnosed Incidence Rate of Breast Cancer, Ages ≥20 Years, Women,

Cases per 100,000 Population, 2013 ........................................................................................... 73

Figure 13: 8MM, Five-Year Diagnosed Prevalent Cases of Breast Cancer, Ages ≥20 Years, Women, N,

2013–2023 .................................................................................................................................. 75

Figure 14: 8MM, Five-Year Diagnosed Prevalent Cases of Breast Cancer by Menopausal Status, Ages ≥20

Years, Women, N, 2013 .............................................................................................................. 76


Table of Contents


Figure 15: 8MM, Five-Year Diagnosed Prevalent Cases of Breast Cancer by Hormone Receptor Subtypes,

Ages ≥20 Years, Women, N, 2013 ............................................................................................... 78

Figure 16: Primary Completion Dates of Active Phase III Clinical Trials for Tykerb ...................................... 121

Figure 17: Active Late-Stage Clinical Trials for Perjeta ............................................................................... 126

Figure 18: Active Phase III Clinical Trials for Kadcyla ................................................................................. 131

Figure 19: Active Phase III Clinical Trials for Afinitor ................................................................................... 135

Figure 20: Clinical Trials for Halaven .......................................................................................................... 145

Figure 21: HER2-Positive Breast Cancer – Phase II–III Pipeline, 2013 ....................................................... 166

Figure 22: Gilotrif’s Clinical Development in Breast Cancer ........................................................................ 167

Figure 23: Clinical and Commercial Positioning of Gilotrif ........................................................................... 170

Figure 24: Neratinib’s Clinical Development ............................................................................................... 172

Figure 25: Clinical and Commercial Positioning of neratinib. ....................................................................... 174

Figure 26: Global Sales ($m) of Branded Products for HER2-Positive Breast Cancer by Company, 2013–2023

................................................................................................................................................. 200

Figure 27: Company Portfolio Gap Analysis in HER2-Positive Breast Cancer, 2013–2023 .......................... 201

Figure 28: Global Sales for HER2-Positive Breast Cancer by Region, 2013–2023 ...................................... 217

Figure 29: Global Sales for HER2-Positive Breast Cancer by Drug Class, 2013–2023 ................................ 218

Figure 30: Sales for HER2-Positive Breast Cancer in the US by Drug Class, 2013–2023............................ 224

Figure 31: Sales for HER2-Positive Breast Cancer in France by Drug Class, 2013–2023 ........................... 230

Figure 32: Sales for HER2-Positive Breast Cancer in Germany by Drug Class, 2013–2023 ........................ 235

Figure 33: Sales for HER2-Positive Breast Cancer in Italy by Drug Class, 2013–2023 ................................ 240

Figure 34: Sales for HER2-Positive Breast Cancer in Spain by Drug Class, 2013–2023 ............................. 245


Table of Contents


Figure 35: Sales for HER2-Positive Breast Cancer in the UK by Drug Class, 2013–2023............................ 250

Figure 36: Sales for HER2-Positive Breast Cancer in Japan by Drug Class, 2013–2023 ............................. 256

Figure 37: Sales for HER2-Positive Breast Cancer in China by Drug Class, 2013–2023 ............................. 261



Introduction

2 Introduction

2.1 Catalyst

HER2-positive breast cancer is the second most common cancer in the world and the most

common cancer in women worldwide. When diagnosed at a very early stage, the prognosis is

positive, with a five-year survival rate of nearly 100%. However, in the later stages of the disease,

survival rapidly decreases. HER2-positive breast cancer is aggressive, and historically, has had a

worse overall survival (OS) compared with HER2-negative disease, which is considered to be less

aggressive. In 1998, the launch of the first HER2-targeted therapy, Herceptin (trastuzumab),

revolutionized the treatment of the disease, bringing the OS close to that of HER2-negative breast

cancer. The realization that introducing HER2-targeted therapies earlier into the disease

management strategy could improve disease-free survival (DFS) has created a large market for

HER2-directed therapies. Today, HER2-positive breast cancer patients are living longer with their

disease, thanks to established disease management strategies using numerous combinations of

chemotherapy with Herceptin and the tyrosine kinase inhibitor (TKI), Tykerb (lapatinib). During the

forecast period from 2013–2023, GlobalData expects that the HER2-positive market will grow due

to the aging populations in the US, 5EU, Japan, and China.

Furthermore, with the new premium-priced agents, such as Perjeta (pertuzumab) and Kadcyla

(ado-trastuzumab emtansine) becoming established in the early lines of metastatic disease,

physicians will have additional treatment options for patients. More therapies will be used in the

neoadjuvant and adjuvant settings, and several pipeline agents are also being investigated in the

non-metastatic market in this disease. A number of these agents are looking to address the

greatest unmet need for HER2-positive breast cancer patients — brain metastases — which

typically occur in the later lines of metastatic therapy and are caused by increasingly resistant

disease.

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

The realization that introducing HER2-targeted therapies earlier into the disease management strategy could improve disease-free survival (DFS) has created a large market for HER2-directed therapies.



Introduction

GlobalData (2013). Bladder Cancer – Opportunity Analysis and Forecasts to 2017, December

2013, GDHC014POA

2.3 Upcoming Related Reports

GlobalData (Q3 2014). HER2-Negative Breast Cancer – Global Drug Forecast and Market

Analysis to 2023

GlobalData (Q3 2014). Renal Cell Carcinoma – Global Drug Forecast and Market Analysis to

2023


Appendix


11.8 About GlobalData

GlobalData is a leading global provider of business intelligence in the healthcare industry.

GlobalData provides its clients with up-to-date information and analysis on the latest developments

in drug research, disease analysis, and clinical research and development. Our integrated business

intelligence solutions include a range of interactive online databases, analytical tools, reports, and

forecasts. Our analysis is supported by a 24/7 client support and analyst team.

GlobalData has offices in New York, San Francisco, Boston, London, India, Korea, Japan,

Singapore, and Australia.

11.9 Disclaimer

All Rights Reserved.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any

form by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior

permission of the publisher, GlobalData.

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