Advances in the

Biologics Market 2014

May 2014

A Business Monitor International Company

World Leaders in Health Industry Analysis

Advances in the Biologics Market 2014

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ADVANCES IN THE BIOLOGICS MARKET 2014

Contents
Foreword ............................................................................................................................................... 1
Executive Summary .............................................................................................................................. 3
Advances in the Biologics Market ....................................................................................................... 4
Market Overview ...................................................................................................................................................................... 4
Sales Analysis...................................................................................................................................................................... 4
Key Biologic Products ........................................................................................................................................................................ 6

Pipeline Analysis ...................................................................................................................................................................... 8

The Key Players ....................................................................................................................................................................... 11
Roche ................................................................................................................................................................................... 11
Amgen ................................................................................................................................................................................ 13
Sanofi................................................................................................................................................................................... 15
AbbVie ................................................................................................................................................................................ 16
Johnson & Johnson ........................................................................................................................................................ 17
Eli Lilly.................................................................................................................................................................................. 19
Antibody-Drug Conjugates ...............................................................................................................21
The Key Players ................................................................................................................................................................ 21
ImmunoGen ....................................................................................................................................................................................... 21
Seattle Genetics................................................................................................................................................................................. 22
Genentech (Roche) .......................................................................................................................................................................... 22
Takeda .................................................................................................................................................................................................. 22

Companies to Watch ..................................................................................................................................................... 23

Mersana Therapeutics ..................................................................................................................................................................... 23
Sorrento Therapeutics .................................................................................................................................................................... 23

Approved ADCs ............................................................................................................................................................... 24

Kadcyla (trastuzumab emtansine) .............................................................................................................................................. 24
Sales forecast ............................................................................................................................................................................ 25
Adcetris (brentuximab vedotin) .................................................................................................................................................. 25
Sales forecast ............................................................................................................................................................................ 26

ADCs in Clinical Development ................................................................................................................................... 27

Inotuzumab ozogamicin ................................................................................................................................................................ 28
Sales forecast ............................................................................................................................................................................ 28
Clinical trials ............................................................................................................................................................................. 28
Glembatumumab vedotin (CDX-011) ....................................................................................................................................... 29
Clinical trials ............................................................................................................................................................................. 29
Teprotumumab ................................................................................................................................................................................. 30
Clinical trials ............................................................................................................................................................................. 30
RG7593 (DCDT2980S)...................................................................................................................................................................... 31

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Clinical trials .............................................................................................................................................................................. 31
RG7596 (DCDS4501A) ..................................................................................................................................................................... 32
Clinical trials .............................................................................................................................................................................. 32
PSMA ADC ........................................................................................................................................................................................... 33
Clinical trials .............................................................................................................................................................................. 33

Cancer Immunotherapy..................................................................................................................... 34
The Key Players ................................................................................................................................................................ 35
Bristol-Myers Squibb ....................................................................................................................................................................... 35
Merck & Co .......................................................................................................................................................................................... 35
Novartis ................................................................................................................................................................................................ 36
Roche .................................................................................................................................................................................................... 36

Companies to Watch ..................................................................................................................................................... 37

Medigene ............................................................................................................................................................................................ 37
NewLink Genetics ............................................................................................................................................................................. 37

Approved Cancer Immunotherapies .............................................................................................................................. 38

Yervoy (ipilimumab) ........................................................................................................................................................................ 38
Sales forecast ............................................................................................................................................................................ 39
Provenge (sipuleucel-T) ................................................................................................................................................................. 39
Sales forecast ............................................................................................................................................................................ 40

Cancer Immunotherapies in Clinical Development .................................................................................................. 41

Dasiprotimut-T Biovest (BiovaxID) ............................................................................................................................................. 42
Talimogene laherparepvec ........................................................................................................................................................... 43
Sales forecast ............................................................................................................................................................................ 44
Clinical trials .............................................................................................................................................................................. 44
Pembrolizumab (MK-3475) ........................................................................................................................................................... 45
Agreement With Incyte ........................................................................................................................................................... 46
Amgen Collaboration ............................................................................................................................................................. 46
Partnership With Pfizer ........................................................................................................................................................... 46
Nivolumab .......................................................................................................................................................................................... 47
Clinical trials .............................................................................................................................................................................. 47
RG7446 (MPDL3280A) .................................................................................................................................................................... 49
Clinical trials .............................................................................................................................................................................. 49
Tecemotide (L-BLP25) ..................................................................................................................................................................... 50
Clinical trials .............................................................................................................................................................................. 50
MAGE-A3 ASCI ................................................................................................................................................................................... 51
MAGRIT trial results ................................................................................................................................................................. 51
Rindopepimut (CDX-110) .............................................................................................................................................................. 52
AGS-003 ............................................................................................................................................................................................... 53
DCVax-L................................................................................................................................................................................................ 53
MVax ..................................................................................................................................................................................................... 54
Algenpantucel-L ............................................................................................................................................................................... 55
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Clinical trials ............................................................................................................................................................................. 55
Bavituximab ........................................................................................................................................................................................ 56
Clinical trials ............................................................................................................................................................................. 56
CTL019 .................................................................................................................................................................................................. 57
Clinical trials ............................................................................................................................................................................. 57

Fusion Proteins ...................................................................................................................................59

Enbrel (etanercept) .......................................................................................................................................................................... 59
Sales and forecast ................................................................................................................................................................... 60
Biosimilar Etanercept Development .......................................................................................................................................... 60
Orencia (abatacept) ......................................................................................................................................................................... 61
Sales and forecast ................................................................................................................................................................... 61
Eylea (aflibercept) ............................................................................................................................................................................. 62
Sales and forecast ................................................................................................................................................................... 63
Clinical trials ............................................................................................................................................................................. 63
Potential combination therapy ........................................................................................................................................... 64
Alprolix (coagulation factor IX [recombinant], Fc fusion protein) .................................................................................. 64
Clinical trials ............................................................................................................................................................................. 65

Fusion Proteins and Fc-optimised mAbs in Clinical Development ..................................................................... 66

Eloctate (efraloctocog alfa) ........................................................................................................................................................... 66
Clinical trials ............................................................................................................................................................................. 67
Atacicept .............................................................................................................................................................................................. 68

Interferons ..........................................................................................................................................69
IFN for Hepatitis Treatment ................................................................................................................................................ 69
Current Market Leaders ................................................................................................................................................ 69
Novel Investigational IFN ............................................................................................................................................. 71
Peginterferon lambda-1a .............................................................................................................................................................. 71
Clinical trials ............................................................................................................................................................................. 71

IFN for Multiple Sclerosis ..................................................................................................................................................... 72

Current Market Leaders ................................................................................................................................................ 72
IFN in Development for MS ......................................................................................................................................... 73
Plegridy (peginterferon beta-1a) ................................................................................................................................................ 73
Sales forecast ............................................................................................................................................................................ 73
Clinical trials ............................................................................................................................................................................. 74
Relonsiv (interferon beta-1b) ....................................................................................................................................................... 75

Interleukin Inhibitors .........................................................................................................................76

Marketed IL Inhibitors .......................................................................................................................................................... 76
Ilaris (canakinumab)......................................................................................................................................................................... 76
Sales and forecast ................................................................................................................................................................... 77
Actemra/RoActemra (tocilizumab) ............................................................................................................................................ 78
Sales and forecast ................................................................................................................................................................... 78

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Stelara (ustekinumab) ..................................................................................................................................................................... 79
Sales and forecast .................................................................................................................................................................... 79

IL Inhibitors in Clinical Development ............................................................................................................................. 81

Anti-IL-2 .............................................................................................................................................................................. 82
Daclizumab (DAC HYP) ................................................................................................................................................................... 82
Sales forecast ............................................................................................................................................................................ 82
Clinical trials .............................................................................................................................................................................. 82

Anti-IL-5 .............................................................................................................................................................................. 83
Mepolizumab ..................................................................................................................................................................................... 83
Sales forecast ............................................................................................................................................................................ 83
Clinical trials .............................................................................................................................................................................. 84
Benralizumab (MEDI-563).............................................................................................................................................................. 85
Clinical trials .............................................................................................................................................................................. 85

Anti-IL-6 .............................................................................................................................................................................. 86
Sarilumab (REGN88, SAR153191) ............................................................................................................................................... 86
Clinical trials .............................................................................................................................................................................. 86
Sirukumab (CNTO 136) ................................................................................................................................................................... 87
Clinical trials .............................................................................................................................................................................. 88

Anti-IL-13 ........................................................................................................................................................................... 88
Lebrikizumab ..................................................................................................................................................................................... 88
Clinical trials .............................................................................................................................................................................. 88

Anti-IL-17 ........................................................................................................................................................................... 89
Brodalumab (MEDI6365; AMG-827; KHK4827) ...................................................................................................................... 89
Sales forecast ............................................................................................................................................................................ 89
Clinical trials .............................................................................................................................................................................. 90
Ixekizumab (LY2439821)................................................................................................................................................................ 90
Sales forecast ............................................................................................................................................................................ 91
Clinical trials .............................................................................................................................................................................. 91
Secukinumab (AIN457) ................................................................................................................................................................... 92
Clinical trials .............................................................................................................................................................................. 93

Anti-IL-23 ........................................................................................................................................................................... 94
Guselkumab (CNTO 1959) ............................................................................................................................................................. 94
Clinical trials .............................................................................................................................................................................. 95
Tildrakizumab .................................................................................................................................................................................... 96
Clinical trials .............................................................................................................................................................................. 96

Monoclonal Antibodies ..................................................................................................................... 97

Established Key Products .................................................................................................................................................... 97
Humira (adalimumab)..................................................................................................................................................................... 97
Sales and forecast .................................................................................................................................................................... 97
Avastin (bevacizumab) ................................................................................................................................................................... 98

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Sales and forecast ................................................................................................................................................................... 98
Erbitux (cetuximab) ......................................................................................................................................................................... 99
Sales and forecast ................................................................................................................................................................. 100
Remicade (infliximab) ................................................................................................................................................................... 100
Sales and forecast ................................................................................................................................................................. 100
Lucentis (ranibizumab) ................................................................................................................................................................. 101
Sales and forecast ................................................................................................................................................................. 101
MabThera/Rituxan (rituximab) .................................................................................................................................................. 103
Sales and forecast ................................................................................................................................................................. 103
Herceptin (trastuzumab) .............................................................................................................................................................. 104
Sales and forecast ................................................................................................................................................................. 104

Biosimilar mAb Development ................................................................................................................................. 105

Adalimumab ..................................................................................................................................................................................... 105
Bevacizumab .................................................................................................................................................................................... 106
Cetuximab ......................................................................................................................................................................................... 106
Infliximab ........................................................................................................................................................................................... 106
Rituximab .......................................................................................................................................................................................... 107
Trastuzumab..................................................................................................................................................................................... 108

Recent Approvals and Potential Therapies ............................................................................................................... 109

CD20 Antibodies .......................................................................................................................................................... 115
Gazyva (obinutuzumab) ............................................................................................................................................................... 115
Sales forecast .......................................................................................................................................................................... 115
Clinical trials ........................................................................................................................................................................... 116
Ocrelizumab (RG1594) .................................................................................................................................................................. 117
Sales forecast .......................................................................................................................................................................... 117
Clinical trials ........................................................................................................................................................................... 117

EGFr Antibodies ............................................................................................................................................................ 118

Necitumumab (LY3012211)......................................................................................................................................................... 118
Sales forecast .......................................................................................................................................................................... 119
Clinical trials ........................................................................................................................................................................... 119

HER2 Antibodies........................................................................................................................................................... 120

Perjeta (pertuzumab) .................................................................................................................................................................... 120
Sales and forecast ................................................................................................................................................................. 120

VEGF Antibodies ........................................................................................................................................................... 121

Cyramza (ramucirumab) .............................................................................................................................................................. 121
Sales forecast .......................................................................................................................................................................... 121
Clinical trials ........................................................................................................................................................................... 122

PCSK9 Antibodies ........................................................................................................................................................ 122

Alirocumab (SAR236553, REGN727) ......................................................................................................................................... 122
Sales forecast .......................................................................................................................................................................... 123
Clinical trials ........................................................................................................................................................................... 124
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Evolocumab (AMG 145) ................................................................................................................................................................ 124
Sales forecast ......................................................................................................................................................................... 125
Clinical trials ........................................................................................................................................................................... 125
Bococizumab (RN316, PF-04950615) ........................................................................................................................................ 128
Clinical trials ........................................................................................................................................................................... 128

BiTE Antibodies............................................................................................................................................................. 129

Blinatumomab (AMG 103) ........................................................................................................................................................... 129
Sales forecast ......................................................................................................................................................................... 129
Clinical trials ........................................................................................................................................................................... 130

CD22 Antibodies .......................................................................................................................................................... 131

Epratuzumab .................................................................................................................................................................................... 131
Sales forecast ......................................................................................................................................................................... 131
Clinical trials ........................................................................................................................................................................... 131
Moxetumomab pasudotox (CAT8015) ..................................................................................................................................... 133
Clinical trials ........................................................................................................................................................................... 133

CD38 Antibodies .......................................................................................................................................................... 134

Daratumumab (JNJ-54767414) .................................................................................................................................................. 134
Clinical trials ........................................................................................................................................................................... 134

Amyloid Beta Antibodies .......................................................................................................................................... 135

Solanezumab (LY2062430) ........................................................................................................................................................... 135
Sales forecast ......................................................................................................................................................................... 135
Clinical trials ........................................................................................................................................................................... 135
Gantenerumab (RG1450) ............................................................................................................................................................. 136
Clinical trials ........................................................................................................................................................................... 136

Antibodies Targeting the Met Pathway............................................................................................................... 137

Onartuzumab (RG3638) ................................................................................................................................................................ 137
Clinical trials ........................................................................................................................................................................... 137
Rilotumumab (AMG 102) .............................................................................................................................................................. 138
Sales forecast ......................................................................................................................................................................... 138
Clinical trials ........................................................................................................................................................................... 138

Peptides/Peptibody ......................................................................................................................... 139

Glucagon-like Peptide Agonists ............................................................................................................................. 139
Eperzan/Tanzeum (albiglutide) ................................................................................................................................................. 139
Sales forecast ......................................................................................................................................................................... 140
Clinical trials ........................................................................................................................................................................... 140
Dulaglutide (LY2189265) ............................................................................................................................................................. 142
Sales forecast ......................................................................................................................................................................... 142
Clinical trials ........................................................................................................................................................................... 142

Ang1/Ang2 Inhibitor .................................................................................................................................................. 144

Trebananib (AMG 386) .................................................................................................................................................................. 144

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Sales forecast .......................................................................................................................................................................... 144
Clinical trials ........................................................................................................................................................................... 144

Appendix: Biologics Pipeline .......................................................................................................... 146

Sources ............................................................................................................................................. 153

List of Tables
Blockbuster Biologics by Sales, 2013 (US$ Million) ..................................................................................................... 7
Biologics Pipeline by Therapy Area, 2014 ....................................................................................................................... 8
Biologics Pipeline by Company, 2014 ............................................................................................................................ 10
Roche Key Biologic Products by Sales, 2012-2013 (US$ Million) .......................................................................... 12
Amgen Key Biologic Products by Sales, 2012-2013 (US$ Million) ........................................................................ 13
Sanofi Key Biologic Products by Sales, 2012-2013 (US$ Million) .......................................................................... 15
AbbVie Key Biologic Products by Sales, 2012-2013 (US$ Million) ........................................................................ 16
J&J Key Biologic Products by Sales, 2012-2013 (US$ Million) ................................................................................ 17
Eli Lilly Key Biologic Products by Sales, 2012-2013 (US$ Million) ......................................................................... 19
ADC Pipeline Summary........................................................................................................................................................ 27
Cancer Immunotherapy Pipeline Summary ................................................................................................................. 41
Enbrel Sales, 2009-2013 (US$ Million) ............................................................................................................................ 60
Orencia Sales, 2009-2013 (US$ Million) ......................................................................................................................... 61
Fusion Protein and Fc-Optimised mAbs Pipeline Summary .................................................................................. 66
Sales of Leading IFN Alfa Products, 2009-2013 (US$ Million) ................................................................................ 70
Leading IFN Beta Product Sales, 2009-2013 (US$ Million) ...................................................................................... 72
Ilaris Sales, 2012-2020 (US$ Million) ................................................................................................................................ 77
Actemra/RoActemra Sales, 2009-2013 (CHF & US$ Million) ................................................................................... 78
Stelara Sales, 2010-2016 (US$ Million) ........................................................................................................................... 79
IL Inhibitors Pipeline Summary ......................................................................................................................................... 81
Humira Sales, 2009-2013 (US$ Million) .......................................................................................................................... 98
Avastin Sales, 2009-2013 (CHF & US$ Million) ............................................................................................................. 99
Erbitux Sales by Company, 2009-2013 (EUR & US$ Million) ................................................................................ 100
Remicade Sales by Company, 2009-2013 (US$ Million) ........................................................................................ 101
Lucentis Sales, 2009-2013 (CHF & US$ Million) ........................................................................................................ 102
Rituxan/MabThera Sales, 2009-2013 (CHF & US$ Million) ................................................................................... 103
Herceptin Sales, 2009-2013 (CHF & US$ Million) ..................................................................................................... 105
mAb Pipeline by Target and Indication ...................................................................................................................... 109
mAb Pipeline by Therapy Area ...................................................................................................................................... 112
Biologics in Clinical Development, 2014 .................................................................................................................... 146

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List of Figures
Biologics Sales by Therapy Area, 2013 (US$ Billion) .................................................................................................... 4
Biologics Sales by Therapy Area, 2013 (%) ..................................................................................................................... 5
Biologics Sales by Company, 2013 (%) ............................................................................................................................. 5
Biologics Clinical Pipeline by Therapy Area, 2014 (%) ................................................................................................ 9
Clinical Pipeline by Development Status, 2014 (%)..................................................................................................... 9
Biologics Pipeline by Company, 2014 (%)..................................................................................................................... 11
Roche Key Biologic Products, 2013 (US$ Million)....................................................................................................... 12
Roche Key Biologic Products, 2020 (US$ Million)....................................................................................................... 13
Amgen Key Biologic Products, 2013 (US$ Million) .................................................................................................... 14
Amgen Key Biologic Products, 2020 (US$ Million) .................................................................................................... 14
Sanofi Key Biologic Products, 2013 (US$ Million)....................................................................................................... 15
Sanofi Key Biologic Products, 2020 (US$ Million)....................................................................................................... 16
AbbVie Humira Sales, 2013 & 2020 (US$ Million) ....................................................................................................... 17
J&J Key Biologic Products, 2013 (US$ Million) ............................................................................................................. 18
J&J Key Biologic Products, 2016 (US$ Million) ............................................................................................................. 18
Eli Lilly Key Biologic Products, 2013 ................................................................................................................................ 19
Eli Lilly Key Biologic Products, 2020 ................................................................................................................................ 20
Kadclya Sales Forecast, 2014-2020 (US$ Million) ....................................................................................................... 25
Adcetris Sales Forecast, 2014-2020 (US$ Million) ...................................................................................................... 26
Inotuzumab Ozogamacin Sales Forecast, 2014-2020 (US$ Million) .................................................................... 28
Yervoy Sales Forecast, 2014-2020 (US$ Million) ......................................................................................................... 39
Provenge Sales Forecast, 2014-2020 (US$ Million).................................................................................................... 40
Talimogene Lahaparepvec Sales Forecast, 2015-2020 (US$ Million) .................................................................. 44
Enbrel Sales Forecast, 2014-2020 (US$ Million) .......................................................................................................... 60
Orencia Sales Forecast, 2014-2020 (US$ Million) ....................................................................................................... 62
Eylea Sales Forecast, 2014-2020 (US$ Million) ............................................................................................................ 63
Sales Forecast for IFN Alfa Products, 2014-2020 (US$ Million) .............................................................................. 70
Leading IFN Beta Product Sales Forecast, 2014-2020 (US$ Million) .................................................................... 73
Plegridy Sales Forecast, 2014-2019 (US$ Million) ...................................................................................................... 74
Ilaris Sales Forecast, 2014-2020 (US$ Million) .............................................................................................................. 77
Actemra/RoActemra Sales Forecast, 2014-2020 (US$ Million) .............................................................................. 79
Stelara Sales Forecast, 2013-2016 (US$ Million) ......................................................................................................... 80
Daclizumab Sales Forecast, 2015-2020 (US$ Million) ............................................................................................... 82
Mepolizumab Sales Forecast, 2015-2020 (US$ Million) ........................................................................................... 84
Brodalumab Sales Forecast, 2016-2020 (US$ Million) .............................................................................................. 89
Ixekizumab Sales Forecast, 2014-2020 (US$ Million) ................................................................................................ 91
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Humira Sales Forecast, 2014-2020 (US$ Million) ........................................................................................................ 98
Avastin Sales Forecast, 2014-2020 (US$ Million) ........................................................................................................ 99
Lucentis Sales Forecast, 2014-2020 (US$ Million) ................................................................................................... 102
MabThera/Rituxan Sales Forecast, 2014-2020 (US$ Million) ............................................................................... 104
Herceptin Sales Forecast, 2014-2020 (US$ Million) ................................................................................................ 105
Gazyva Sales Forecast, 2014-2020 (US$ Million)...................................................................................................... 116
Ocrelizumab Sales Forecast, 2015-2020 (US$ Million) .......................................................................................... 117
Necitumumab Sales Forecast, 2015-2020 (US$ Million) ....................................................................................... 119
Perjeta Sales Forecast, 2014-2020 (US$ Million) ...................................................................................................... 120
Cyramza Sales Forecast, 2014-2020 (US$ Million)................................................................................................... 121
Alirocumab Sales Forecast, 2015-2020 (US$ Million)............................................................................................. 123
Evolocumab Sales Forecast, 2014-2020 (US$ Million) ........................................................................................... 125
Blinatumomab Sales Forecast, 2014-2020 (US$ Million) ...................................................................................... 129
Epratuzumab Sales Forecast, 2014-2020 (US$ Million) ......................................................................................... 131
Solanezumab Sales Forecast, 2017-2020 (US$ Million)......................................................................................... 135
Rilotumumab Sales Forecast, 2017-2020 (US$ Million) ........................................................................................ 138
Eperzan Sales Forecast, 2014-2020 (US$ Million) .................................................................................................... 140
Dulaglutide Sales Forecast, 2015-2018 (US$ Million) ............................................................................................ 142
Trebananib Sales Forecast, 2015-2018 (US$ Million) ............................................................................................. 144

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Executive Summary
The global biologics market is estimated to be worth around US$175 billion. The market is
characterised by high-value products that treat chronic and often life-threatening diseases, and is
expected to continue to grow faster than the overall pharmaceutical market.
The highest revenue generators are biological medicines used in the treatment of autoimmune and
inflammatory disorders, cancer and diabetes. In terms of total biologic revenues, the leading
companies are Roche, Amgen and Sanofi. In 2013, the top three biologics by global sales value were
AbbVies Humira, with sales of US$10,659 million; MabThera/Rituxan (rituximab), which is marketed
by both Roche and Biogen Idec and had global sales of US$8,932 million; and Enbrel (etanercept),
which is marketed by Amgen and Pfizer, with combined total sales of US$8,325 million.
More than 280 potential novel biologic therapies have been identified in the clinical pipeline, almost
half of which are being evaluated for oncology indications. These include immunotherapies,
antibody-drug conjugates (ADCs), bispecific T-cell engager (BiTE) antibodies (Abs) and monoclonal
Abs (mAbs).
Cancer immunotherapy has become a hot topic over the last few months as several promising
candidates have made progress through the clinical pipeline. Bristol-Myers Squibb, which has already
achieved success in this field with its breakthrough melanoma therapy, Yervoy (ipilimumab), believes
that immuno-oncology has the potential to transform the treatment of cancer and the company has
an extensive clinical pipeline and discovery programmes dedicated to maximising this field of
research.
Another advance in cancer care is the emergence of ADCs, the first of which have been approved:
Roches Kadcyla (trastuzumab emtansine) and Seattle Genetics Adcetris (brentuximab vedotin).
ADCs combine therapeutic Abs with small molecule drugs and the technology being developed in
oncology indications is designed to harness the targeting ability of mAbs to deliver cell-killing agents
directly to cancer cells. ADCs are intended to spare non-targeted cells, thereby reducing many of the
toxic effects of traditional chemotherapy, while potentially enhancing anti-tumour activity.
Bispecific-Abs bind to two different epitopes either on the same, or on different targets, which may
improve the Abs' specificity and efficacy in inactivating the disease targets. In particular, BiTE
antibodies, which are designed to direct the body's cytotoxic, or cell-destroying, T-cells against
tumour cells, represent a new therapeutic approach to cancer therapy.
In parallel to the development of novel therapies, biosimilar versions of a number of established,
blockbuster mAbs are in development. The market for the first wave of biosimilars has been relatively
small, but the potential for biosimilar mAbs has attracted investment from major pharmaceutical
companies. Recent advances include the approval of the first biosimilar infliximab in Europe in
September 2013, under the brand names Remsima and Inflectra. Originally developed by Celltrion in
South Korea as Remsima, Hospira has the rights to Inflectra in Europe and certain CIS countries, as
well as the US, Canada, Australia and New Zealand. Inflectra has been launched in a number of CIS
countries, where it is being marketed by Alvogen.
This report aims to provide a comprehensive overview of recent advances in the biologics market, the
key players and some highly successful, multi-billion dollar therapies. In this context, the report
examines promising novel therapies and the development of the next-generation of biosimilars.

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Biologics Pipeline by Company, 2014 (%)
Genentech/Roche
9.9%
Eli Lilly
9.5%

Other
43.7%

Sano/Genzyme
8.5%

MedImmune
(AstraZeneca)
6.7%
Bristol-Myers
Squibb
4.9%

Amgen
4.9%

Pzer
6.0%

GlaxoSmithKline
6.0%

Source: Company reports, clinicaltrials.gov, BMI

The Key Players

Roche
Roche is the worlds largest supplier of biologic medicines. In October 2013, Roche announced plans
to expand its domestic biotech product manufacturing capacity, investing CHF 800 million (US$640
million) in its Basel (Switzerland) and Penzberg (Germany) sites, initially to boost its anti-cancer
product production.
The company stated that its investment would support increasing demand for its licensed biologic
medicines, such as RoActemra (tocilizumab), Kadcyla (trastuzumab emtansine) and Perjeta
(pertuzumab), as well as providing a strong foundation for the delivery of the investigational biologic
medicines in its pipeline.
In November 2013, Roche announced that Kadcyla, the latest targeted medicine from its HER2
franchise and its first antibody-drug conjugate (ADC) had been approved by the European
Commission (EC) for people with previously treated HER2-positive advanced breast cancer. Kadcyla
was approved by the FDA in February 2013.
In October 2013, the FDA granted Roche's Perjeta accelerated approval for use before surgery in
patients with HER2-positive early-stage breast cancer.
In September 2013, Roche's new injectable formulation of Herceptin was approved by the European
Commission for HER2-positive breast cancer. The new formulation is aimed at reducing the time
patients will spend in hospital.

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Pfizer stated that it would continue evaluation of inotuzumab ozogamicin in other haematologic
malignancies. Inotuzumab ozogamicin, administered on a weekly basis, three weeks out of four,
continues to be evaluated in adult acute lymphoblastic leukaemia (ALL). The INO-VATE ALL study
(B1931022) is an open-label, randomised, Phase III study of inotuzumab ozogamicin compared with a
defined investigator's choice of chemotherapy in adult patients with relapsed or refractory CD22+
ALL.

Glembatumumab vedotin (CDX-011)

INN
Brand name
Lab code
Developer
Status
Therapy area
Mode of delivery
Indications

glembatumumab vedotin
n/a
CDX-011
Celldex Therapeutics
Phase II
Oncology
IV infusion
Locally advanced or metastatic breast cancer; metastatic melanoma

Glembatumumab vedotin (CDX-011) is a fully human mAb-drug conjugate that targets glycoprotein
NMB (GPNMB), currently being developed by Celldex Therapeutics. GPNMB is a protein overexpressed by multiple tumour types, including breast cancer and melanoma. GPNMB has been
shown to be associated with the ability of the cancer cell to invade and metastasise and to correlate
with reduced time to progression and survival in breast cancer (BC). Glembatumumab vedotin is in
development for the treatment of locally advanced or metastatic BC, with an initial focus in triplenegative disease.
The ADC technology used in glembatumumab vedotin, comprising monomethyl-auristatin E (MMAE)
and a stable linker system for attaching it to CR011, was licensed from Seattle Genetics.
Glembatumumab vedotin is designed to be stable in the bloodstream, but to release MMAE upon
internalisation into GPNMB-expressing tumour cells, resulting in a targeted cell-killing effect.
In May 2010, the FDA granted fast track designation to glembatumumab vedotin for the treatment of
advanced, refractory/resistant GPNMB-expressing BC. The compound is also in development for the
treatment of Stage III and IV melanoma.

Clinical trials
In December 2013, Celldex Therapeutics reported the launch of a randomised study (METRIC) of
glembatumumab vedotin in patients with metastatic triple-negative breast cancers (TNBCs) that
overexpress GPNMB. The trial was initiated in the US, with additional sites planned in Canada and
Australia. The study is expected to include up to 100 sites and will enrol approximately 300 patients.
METRIC is a pivotal, open-label, prospectively controlled, randomised study of glembatumumab
vedotin in patients with metastatic GPNMB-expressing TNBC. Eligible patients must have received no
more than one prior line of chemotherapy for advanced disease and therapy must have included a
taxane and anthracycline. Patients will be randomised (2:1) to receive glembatumumab vedotin or
capecitabine. Study treatment will continue until disease progression or intolerance with tumour
assessments performed at six-week intervals for six months and nine-week intervals thereafter. The
primary objective is to evaluate the anticancer activity of glembatumumab vedotin as measured by
the objective response rate (ORR) and duration of progression-free survival (PFS). The study is
designed to enable Celldex to apply for registration with positive results for either endpoint.
Secondary endpoints include duration of response, overall survival (OS), safety and tolerability. The
company will also assess improvements in quality of life and/or cancer-related pain as exploratory
endpoints.

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ADVANCES IN THE BIOLOGICS MARKET 2014

Actemra/RoActemra Sales Forecast, 2014-2020 (US$ Million)
3,500
2,980

3,000

2,760

US$ Million

2,500

2,300
2,069
1,837

2,000
1,590
1,500

1,299

1,000
500
0
2014

2015

2016

2017

2018

2019

2020

Source: Bloomberg, Espicom

Stelara (ustekinumab)
INN
Brand name
Companies
Market approvals:
US
EU
Therapy area
Mode of delivery
Indications

ustekinumab
Stelara
Janssen (J&J)
Sep-2009
Jan-2009
Autoimmune, inflammatory disorders
SC injection
Moderate-to-severe plaque psoriasis; active psoriatic arthritis

Stelara (ustekinumab) is a human IgG1 mAb that binds with specificity to the p40 protein subunit
used by both the IL-12 and IL-23 cytokines. IL-12 and IL-23 are naturally occurring cytokines that are
involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell
differentiation and activation. Stelara is indicated for the treatment of plaque psoriasis and active
psoriatic arthritis.

Sales and forecast

Sales of Stelara have grown strongly since its launch and it has become a key contributor to Johnson
& Johnsons immunology portfolio. In 2013, J&J reported global sales amounting to US$1,504 million,
an increase of 46.7% over the previous year. Consensus forecasts suggest that sales will continue to
increase year-on-year, rising to US$2,396 million by 2016.

Stelara Sales, 2010-2016 (US$ Million)

J&J sales (US$ million)

% change

2010

2011

2012

2013

2014

2015

2016

393

738

1,025

1,504

1,869

2,151

2,396

87.8

38.9

46.7

24.3

15.1

11.4

Source: Company reports, Bloomberg, Espicom

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ADVANCES IN THE BIOLOGICS MARKET 2014

Recent Approvals and Potential Therapies

Espicom has identified more than 100 mAbs in clinical development. While cancer and
autoimmune/inflammatory disorders remain key therapy areas for mAbs, there are also novel mAbs
being developed to treat Alzheimers disease, as well as for cardiovascular and respiratory indications.

mAb Pipeline by Target and Indication

Name
gantenerumab
(RG1450)
solanezumab
(LY2062430)
crenezumab (RG7412)

Developer
Roche

Target
Abeta

Indications
Alzheimer's disease

Status
Phase III

Eli Lilly

Abeta

Alzheimer's disease

Phase III

Abeta

Alzheimer's disease

Phase II

GSK933776
BIIB037
BAN2401

Genentech
(Roche)
GlaxoSmithKline
Biogen Idec
Biogen Idec; Eisai

Geographic retinal atrophy

Alzheimer's disease
Alzheimer's disease

Phase II
Phase I
Phase II

BAN2401

Eisai

Alzheimer's disease

Phase II

bimagrumab
(BYM338)
namilumab (MT203)
MEDI4893

Novartis

Abeta
Abeta
Abeta
protofibrils
Abeta
protofibrils
ActRIIB

Sporadic inclusion body

myositis (sIBM)
Rheumatoid arthritis
S. aureus infection

Phase II

Ulcerative colitis; Crohn's

disease
Crohn's disease, ulcerative
collitis
Solid tumours

Filed

Solid tumours
Influenza A

Phase I
Phase II
Phase II

vedolizumab
(MLN0002)
MEDI7183; AMG 181
MEDI3617
SAR307746
RG7745
belimumab

Takeda
MedImmune
(AstraZeneca)
Takeda
Amgen;
MedImmune
MedImmune
(AstraZeneca)
Sanofi
Genentech
(Roche)
GlaxoSmithKline

AGM-CSF
alfa toxin
alfa4-beta7
integrin
alfa4-beta7
Ang2
ANG2
Anti-influenza A
mAb
B lymphocyte

Phase I
Phase I

Phase II
Phase I

Amgen;
MedImmune
Eli Lilly

B7RP-1

Myasthenia gravis; idiopathic

membranous nephropathy
Systemic lupus erythematosus

BAFF

Lupus; multiple myeloma

Phase III

Eli Lilly
Merck & Co

c-Met
C.difficile

Cancer
C.difficile infection

Phase II
Phase III

Novartis
Sanofi
Sanofi

C5
CA6
CD-19

Phase II
Phase I
Phase II

XmAb5871
MEDI-551

Xencor
MedImmune
(AstraZeneca)

CD19
CD19

XmAb5574; MOR208

MorphoSys

CD19

MEDI-551

MedImmune
(AstraZeneca)
Genentech

CD19

Ophthalmology
Solid tumours
B-cell refractory/relapsed
malignancies (NHL, ALL)
Rheumatoid arthritis
Chronic lymphocytic
leukaemia (CLL); diffuse large
B-cell lymphoma (DLBCL)
B-cell acute lymphoblastic
leukaemia (B-ALL); nonHodgkins lymphoma (NHL)
Multiple sclerosis (RRMS)

CD20

Multiple sclerosis: RRMS, PPMS

Phase III

MEDI5872; AMG 557

tabalumab
(LY2127399)
LY2875357
actoxumab+bezlotoxu
mab (MK-3415A)
LFG316
SAR566658
SAR3419

ocrelizumab (RG1594)

Phase I

Phase II
Phase II

Phase II

Phase I

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