Advances in the Biologics Market 2014 - Sample

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Advances in the Biologics Market 2014

May 2014

Advances in the Biologics Market 2014 © Copyright 2014 Espicom Business Intelligence

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ADVANCES IN THE BIOLOGICS MARKET 2014

© espicom BUSINESS INTELLIGENCE May 2014 i

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


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


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



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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


Moxetumomab pasudotox (CAT8015) ..................................................................................................................................... 133 Clinical trials ........................................................................................................................................................................... 133

CD38 Antibodies .......................................................................................................................................................... 134 Daratumumab (JNJ-54767414) .................................................................................................................................................. 134

Clinical trials ........................................................................................................................................................................... 134 Amyloid Beta Antibodies .......................................................................................................................................... 135 Solanezumab (LY2062430) ........................................................................................................................................................... 135


Gantenerumab (RG1450) ............................................................................................................................................................. 136 Clinical trials ........................................................................................................................................................................... 136

Antibodies Targeting the Met Pathway ............................................................................................................... 137 Onartuzumab (RG3638) ................................................................................................................................................................ 137

Clinical trials ........................................................................................................................................................................... 137 Rilotumumab (AMG 102) .............................................................................................................................................................. 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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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 AbbVie’s 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: Roche’s 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.



Biologics Pipeline by Company, 2014 (%)

Source: Company reports, clinicaltrials.gov, BMI

The Key Players

Roche Roche is the world’s 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.

Genentech/Roche 9.9%

Eli Lilly 9.5%

Sanofi/Genzyme 8.5%

MedImmune (AstraZeneca)

6.7%

GlaxoSmithKline 6.0%

Pfizer 6.0% Amgen

4.9%

Bristol-‐Myers Squibb 4.9%

Other 43.7%



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 glembatumumab vedotin Brand name n/a Lab code CDX-011 Developer Celldex Therapeutics Status Phase II Therapy area Oncology Mode of delivery IV infusion Indications 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 over-expressed 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 triple-negative 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.



Actemra/RoActemra Sales Forecast, 2014-2020 (US$ Million)

Source: Bloomberg, Espicom

Stelara (ustekinumab) INN ustekinumab Brand name Stelara Companies Janssen (J&J) Market approvals: US Sep-2009 EU Jan-2009 Therapy area Autoimmune, inflammatory disorders Mode of delivery SC injection Indications 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 & Johnson’s 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)

2010 2011 2012 2013 2014 2015 2016

J&J sales (US$ million) 393 738 1,025 1,504 1,869 2,151 2,396

% change - 87.8 38.9 46.7 24.3 15.1 11.4 Source: Company reports, Bloomberg, Espicom

1,299

1,590 1,837

2,069 2,300

2,760 2,980

0

500

1,000

1,500

2,000

2,500

3,000

3,500

2014 2015 2016 2017 2018 2019 2020

US$ M

illion



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 Alzheimer’s disease, as well as for cardiovascular and respiratory indications. mAb Pipeline by Target and Indication Name Developer Target Indications Status gantenerumab (RG1450)

Roche Abeta Alzheimer's disease Phase III

solanezumab (LY2062430)

Eli Lilly Abeta Alzheimer's disease Phase III

crenezumab (RG7412) Genentech (Roche)

Abeta Alzheimer's disease Phase II

GSK933776 GlaxoSmithKline Abeta Geographic retinal atrophy Phase II BIIB037 Biogen Idec Abeta Alzheimer's disease Phase I BAN2401 Biogen Idec; Eisai Abeta

protofibrils Alzheimer's disease Phase II

BAN2401 Eisai Abeta protofibrils

Alzheimer's disease Phase II

bimagrumab (BYM338)

Novartis ActRIIB Sporadic inclusion body myositis (sIBM)

Phase II

namilumab (MT203) Takeda AGM-CSF Rheumatoid arthritis Phase I MEDI4893 MedImmune

(AstraZeneca) alfa toxin S. aureus infection Phase I

vedolizumab (MLN0002)

Takeda alfa4-beta7 integrin

Ulcerative colitis; Crohn's disease

Filed

MEDI7183; AMG 181 Amgen; MedImmune

alfa4-beta7 Crohn's disease, ulcerative collitis

Phase II

MEDI3617 MedImmune (AstraZeneca)

Ang2 Solid tumours Phase I

SAR307746 Sanofi ANG2 Solid tumours Phase I RG7745 Genentech

(Roche) Anti-influenza A mAb

Influenza A Phase II

belimumab GlaxoSmithKline B lymphocyte Myasthenia gravis; idiopathic membranous nephropathy

Phase II

MEDI5872; AMG 557 Amgen; MedImmune

B7RP-1 Systemic lupus erythematosus Phase I

tabalumab (LY2127399)

Eli Lilly BAFF Lupus; multiple myeloma Phase III

LY2875357 Eli Lilly c-Met Cancer Phase II actoxumab+bezlotoxumab (MK-3415A)

Merck & Co C.difficile C.difficile infection Phase III

LFG316 Novartis C5 Ophthalmology Phase II SAR566658 Sanofi CA6 Solid tumours Phase I SAR3419 Sanofi CD-19 B-cell refractory/relapsed

malignancies (NHL, ALL) Phase II

XmAb5871 Xencor CD19 Rheumatoid arthritis Phase II MEDI-551 MedImmune

(AstraZeneca) CD19 Chronic lymphocytic

leukaemia (CLL); diffuse large B-cell lymphoma (DLBCL)

Phase II

XmAb5574; MOR208 MorphoSys CD19 B-cell acute lymphoblastic leukaemia (B-ALL); non-Hodgkin’s lymphoma (NHL)

Phase II

MEDI-551 MedImmune (AstraZeneca)

CD19 Multiple sclerosis (RRMS) Phase I

ocrelizumab (RG1594) Genentech CD20 Multiple sclerosis: RRMS, PPMS Phase III

Advances in the Biologics Market 2014 - Sample

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