View
219
Download
1
Category
Tags:
Preview:
Citation preview
© Datamonitor
the home of Business Intelligence
innovative deliveryexpert analysisquality data
© Datamonitor
Biosimilars: Pipeline TrendsMonoclonal antibodies dominate biosimilar pipelines
December 2011 (HC00149-002)
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
2
About the presentation and report
This executive presentation is a summary of the key analysis in the accompanying written report, which provides more in-depth analysis of the information presented here. The written report is organized into the following chapters:
An executive summary which provides key biosimilar/copy-biologic development metrics
An explanation of the methodology used by Datamonitor in this report
An overview of key biosimilar/copy-biologic molecules in development and launched
The bibliography.
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
3
Key findings (1/3)
• Datamonitor has identified a total of 397 biosimilars/copy-biologics across 125 companies as being in development/marked. Products and pipeline candidates were identified using publically available information (where available). For each candidate, the stage of development was determined using company reported information as well as secondary sources such as clinical trial databases.
• Marketed products – Biosimilar and copy-biologic markets are dominated by versions of simple biologic molecules such as erythropoietin, somatropin, filgrastim and insulin products.
• Pipeline candidates – There is an increasing trend towards the development of high value biologics such as monoclonal antibodies (MAbs), fusion proteins, and second-generation biologics, with 57 MAb biosimilar candidates currently in development, versus only 46 therapeutic protein candidates. Rituximab is the most targeted molecule, with 14 pipeline biosimilar candidates currently in development.
• Target therapy areas/indications – Reflecting the focus on MAbs and therapeutic proteins such as erythropoietin and filgrastim, oncology, neutropenia and anemia as well as various cancer and immunological and inflammatory indications are the most frequently targeted by developers.
• Geography – The EU leads in terms of the number of marketed and pipeline biosimilar candidates followed by South Korea, while India continues to lead the way in the copy-biologics market, followed by China.
• Company – Based on company reported information, Sandoz was highlighted as the leading company in terms of marketed and pipeline biosimilars, while Zydus Cadilla leads in terms of copy-biologic development.
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
4
Key findings (2/3)
Top 5 Biosimilars Number of biosimilars
Copy-biologics Number of copy-biologics
Marketed
1 erythropoietin 7 filgrastim 35
2 somatropin 5 erythropoietin 30
3 filgrastim 4 insulin 23
4 insulin 1 interferon alfa-2b 17
5 follicle-stimulating hormone 1 interleukin-2 8
Pipeline
1 rituximab 14 rituximab 3
2 filgrastim 9 teriparatide 3
3 trastuzumab 8 erythropoietin 2
4 erythropoetin 8 pegfilgrastim 2
5 etanercept 7 darbepoetin alfa 2
Company (marketed and pipeline)
1 Sandoz 13 (4 + 9) Zydus Cadila 15 (5 + 10)
2 Gene Techno Sciences 10 (0 + 10) Cipla 12 (0 + 12)
3 Celltrion 8 (0 + 8) Dr. Reddy's 12 (5 + 7)
4 Harvest Moon 8 (2 + 6) Laboratorios Beta 10 (10 + 0)
5 Teva 6 (1 + 5) Biocad 9 (2 + 7)
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
5
Key findings (3/3)
Top 5 Biosimilars Number of biosimilars
Copy-biologics Number of copy-biologics
Therapy area (marketed and pipeline)
1 Oncology 71 (11 + 60) Oncology 106 (89 + 17)
2 Immunology & Inflammation 35 (0 + 35) Hematology 40 (35 + 5)
3 Hematology 21 (7 + 14) Infectious Diseases 28 (27 + 1)
4 Growth Disorders 9 (5 + 4) Metabolic Disorders 27 (23 + 4)
5 Central Nervous System 4 (1 + 3) Gender Specific Health 22 (19 + 3)
Indication (marketed and pipeline)
1 Neutrapenia 19 (4 + 15) Neutrapenia 46 (43 + 3)
2 Anemia 15 (7 + 8) Anemia 30 (33 + 0)
3 Non-Hodgkin's lymphoma / rheumatoid arthritis 12 (0 + 12)
Diabetes28 (23 + 4)
4 Growth disorders 9 (5 + 4) Hepatitis C 22 (21 + 1)
5 Her-2 positive breast cancer 8 (0 + 8) Infertility 19 (19 + 0)
Geography (marketed and pipeline)
1 EU 66 (9 + 57 India 102 (59 + 43)
2 South Korea 35 (6 + 29) China 50 (39 + 11)
3 US 28 (0 + 28) Argentina 25 (25 + 0)
4 Japan 17 (2 + 15) Russia 15 (8 + 7)
5 Canada 8 (0 + 8) Mexico 14 (13 + 1)
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
6
Definitions and methodology (1/4)
Biologic definitions
Below is a list of definitions used by Datamonitor to classify different types of biologic drug:
Innovative biologic – A novel biologic that has been patented.
Biobetter (biosuperior/second-generation biologic) – An innovative biologic drug that has been structurally and/or functionally altered to achieve an improved or different clinical performance (Biosimilar Medicinal Products Working Party, 2011).
Biosimilar – A copy version of an already authorized biological innovative (biologic/biobetter/biosuperior) drug with demonstrated similarity in physicochemical characteristics, efficacy, and safety, based on a comprehensive comparability exercise, and approved through an official biosimilars pathway (Biosimilar Medicinal Products Working Party, 2011).
Copy-biologic – A copy of an innovative biologic that has been approved in a country where no official biosimilar pathway exists.
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
7
Definitions and methodology (2/4)
Methodology
Source: Datamonitor; company-reported information, 2011
A total of 397 biosimilars/copy-biologics across 125 companies are currently in development/marketed (Table 2). Products and pipeline candidates were identified using the MedTRACK Disease Hub database, company websites, and company annual reports (where available).
For the purpose of this analysis, only drugs in development and at market were included, with drugs that have been discontinued, withdrawn, or refused excluded for the analysis.
Biologic type Development Approved/launched Discontinued, withdrawn, refused, and unknown
Biosimilar 126 20 3
Copy-biologic 60 189 1
Copy-biologic/biologic/biosimilar 2 0 1
Total 188 209 5
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
8
Definitions and methodology (3/4)
Stages of development
For each candidate, the stage of development was determined using company-reported information as well as secondary sources such as clinical trial databases (e.g. ClinicalTrials.gov, Citeline):
Planned – Refers to candidates which companies have explicitly stated they plan to develop, but for which no product development as yet begun.
Development – Refers to candidates in undefined stages of development, and which have yet to be approved/launched.
Preclinical – Refers to products in preclinical development.
Clinical trials/pre-approval – Refers to candidates in Phase I, II, and III clinical trials, as well as those awaiting application for regulatory approval and those awaiting approval by regulatory authorities.
Approved/launched – Refers to products which have received approval from regulatory authorities and may have launched.
Discontinued/withdrawn/refused – Refers to candidates which have been discontinued, withdrawn from the market, withdrawn from development, or have been refused marketing authorization.
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
9
Definitions and methodology (4/4)
Disease indications
For each candidate the target indication was determined as follows:
Where available, Datamonitor has reported the indications for the biosimilar/copy-biologic listed by the company.
Where no information regarding indications was available, Datamonitor has listed all the indications of the reference biologic product.
Geographical regions
For each candidate the target geographical market was determined as follows:
Where available, Datamonitor has reported the geographical region for the biosimilar/copy-biologic listed by the company.
Where no information regarding geographical region was available, Datamonitor listed the geography where the company is headquartered.
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
10
Leading countries in terms of pipeline and marketed biosimilars and copy-biologics
Leading countries for biosimilars and copy-biologics, by stage of development, 2011
Source: Datamonitor; company-reported information, 2011
In terms of pipeline and marketed copy-biologics, India leads the way with 102 products (encompassing 27 molecules), closely followed by China with 50 products (25 molecules), largely driven by the development of cheap simple biologics approved by regulatory authorities in these markets as new drugs.
The EU is the market with the greatest number of pipeline and marketed biosimilar products, totaling 66 (32 molecules) as of December 2011, reflecting the fact that the European Medicines Agency (EMA) was the first developed market to introduce a biosimilars approval pathway in 2005.
South Korea and the US also have sizable biosimilar pipelines.
0
20
40
60
80
100
120
India EU
Chin
a
South
Kor
ea US
Argen
tina
Japan
Russia
Mexic
o
Brazil
Oth
er
Nu
mb
er
of
can
did
ate
s
Planned Development Pre-clinicalClinical trials/ Pre-approval Approved / Launched biosimilars Approved / Launched copy biologics
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
11
Biosimilars by molecule type
Biosimilars development, by stage of development and molecule type, 2011
Source: Datamonitor; company-reported information, 2011
Biosimilar markets are dominated by versions of simple biologic molecules – namely erythropoietin, filgrastim, and somatropin – which are relatively cheap and easy to produce and which have consequently become something of a proof of principle for biosimilars producers, used to test biosimilar pathways.
However, there is an increasing trend towards the development of high value biologics such as MAbs, fusion proteins, and second-generation biologics.
Global monoclonal MAb sales are forecast to reach $63bn in 2015, making this market an attractive target for biosimilar developers, with interest in biosimilar MAbs having intensified since the drafting of the EU MAb guidelines in November 2010. Reflecting this there are currently 57 MAb biosimilar candidates in development, versus only 46 therapeutic protein candidates.
0
10
20
30
40
50
60
70
Therapeuticprotein
Monoclonalantibody
Hormone therapy Insulin Blood factor Unknown atpresent
Nu
mb
er
of
can
did
ate
s
Planned Development Pre-clinical Clinical trials / Pre-approval Approved / Launched
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
12
Copy-biologics by molecule type
Copy-biologics development, by stage of development and molecule type, 2011
Source: Datamonitor; company-reported information, 2011
Copy-biologic markets have historically been dominated by simple biologics such as therapeutic proteins, which are cheap and relatively simple to manufacture.
Only a handful of pharmaceutical companies including Dr. Reddy’s, Zydus Cadila, BioCad, Shanghai CP Guojian Pharmaceutical, and Probiomed have the technology, expertise, and finances to develop copy-biologic MAbs, with Dr. Reddy's Reditux (rituximab) is the world’s first and only copy-biologic MAb.
0
20
40
60
80
100
120
140
160
180
Therapeuticprotein
Insulin Monoclonalantibody
Hormonetherapy
Blood factor Unknown atpresent
Num
ber
of c
andi
date
s
Planned Development Pre-clinical Clinical trials / Pre-approval Approved / Launched
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
13
Rituximab is the biologic most targeted by biosimilar developers
Leading molecules targeted by biosimilar developers
Source: Datamonitor; company-reported information, 2011
Rituximab has received significant attention from biosimilar developers, with 14 candidates at various stages of development (from planned to Phase III clinical trials).
Herceptin (trastuzumab; Roche) is the only MAb used in the treatment of HER2-positive metastatic breast cancer. It has also been a major target for biosimilar developers, with eight candidates currently in development.
Biosimilar developers are also looking to develop other more complex products such as biosimilar versions of second-generation biologics such as pegfilgrastim, darbepoetin alfa, and pegylated interferon alfa. These drugs have improved half-lives and dosing regimens over their first-generation counterparts.
0
2
4
6
8
10
12
14
16
eryth
ropo
ietin
ritux
imab
filgra
stim
som
atro
pin
trast
uzum
ab
etan
erce
pt
pegf
ilgra
stim
inflix
imab
adali
mum
ab
darb
epoe
tin a
lfa
insu
lin
Num
ber
of c
andi
date
s
Planned Development Pre-clinical Clinical trials / Pre-approval Approved / Launched
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
14
Simple biologics dominate the copy-biologic market
Leading molecules targeted by copy-biologic manufacturers, 2011
Source: Datamonitor; company-reported information, 2011
There are currently 36 copy-biologic versions of filgrastim, 31 copy-biologic versions of erythropoietin, and 25 copy-biologic insulins at market, with these products accounting for 49% of all copy-biologics currently available.
Due to the rising prevalence of diabetes in emerging markets, together with the high cost of advanced insulin products such as insulin glargine and lispro, lower cost human insulin and bovine/porcine insulins will continue to prove popular among copy-biologic manufacturers and patients.
Interferon alfa-2a and -2b products have proved to be popular molecules. Hepatitis C virus infection is particularly prevalent in many emerging markets, and as a result companies have tapped into this lucrative market.
0
5
10
15
20
25
30
35
40
filgra
stim
eryt
hrop
oietin
insulin
interfe
ron a
lfa-2
b
inter
leukin
-2
som
atro
pin
inte
rleuk
in-11
pegf
ilgra
stim
inte
rfero
n alfa
-2a
interfe
ron b
eta-
1a
Nu
mb
er
of
can
did
ate
s
Planned Development Pre-clinical Clinical trials / Pre-approval Approved / Launched
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
15
Oncology is the therapy area most targeted by biosimilar developersLeading therapy areas targeted by biosimilar developers, 2011
Source: Datamonitor; company-reported information, 2011
Oncology is currently the focal therapy area for biosimilar developers, with 60 candidates in development and 12 biosimilars already launched. This group represents 11 different molecules across a variety of oncology and associated indications, from simple biologics such as filgrastim to more complex high value targeted therapies such as trastuzumab.
Diseases within the immunology and inflammation field have also received significant attention from biosimilar developers, with 35 candidates currently in development across a number of distinct indications. The molecules for which there is active clinical development within this group include infliximab, etanercept, adalimumab, and rituximab.
0
10
20
30
40
50
60
70
80
Onco
logy
Imm
unology &
Infla
mm
ation
Hemato
logy
Gro
wth D
isord
ers
Cen
tral N
ervous
Sys
tem
Infe
ctious
Dise
ases
Gende
r Spec
ific H
ealth
Meta
bolic
Oth
er Dise
ases
Cardiova
scula
r
Geria
trics
Res
pirato
ry
Unk
nown
Nu
mb
er
of
pro
du
cts
Single therapy area Oncology/Hematology Oncology/Immunology & Inflammation
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
16
Oncology is the therapy area most targeted by copy-biologic manufacturersLeading therapy areas targeted by copy-biologic developers, 2011
Source: Datamonitor; company-reported information, 2011
As with biosimilar developers, oncology is the focal therapy area for copy-biologic manufacturers, with 17 candidates in development and 86 products already launched. This group is primarily made up of copy-biologic versions of molecules. The majority of these products are filgrastim, which are low cost and easy to produce by manufacturers, and affordable to patients.
The infectious disease group consists exclusively of interferon alfa and peginterferon alfa copy-biologics for the treatment of hepatitis C virus infection, which is particularly prevalent in many emerging markets.
0
20
40
60
80
100
120
Oncolog
y
Hemato
logy
Infe
ctiou
s Dise
ases
Met
abolic
Gende
r Spe
cific
Hea
lth
Imm
unolo
gy &
Infla
mm
atio
n
Centra
l Ner
vous
Sys
tem
Cardiov
ascu
lar
Growth
Dis
orders
Oncolog
y/Im
muno
logy &
Infla
mm
ation
Unknown
Nu
mb
er
of
pro
du
cts
Single therapy area Oncology/Hematology Oncology/Immunology & Inflammation
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
17
India dominates the market in terms of approved products
Leading countries for biosimilars and copy-biologics development, 2011
Source: Datamonitor; company-reported information, 2011
In terms of launched copy-biologics, India leads the way with 59 products (encompassing 22 molecules), followed by China with 39 products (16 molecules), followed by the Latin American markets of Argentina, Mexico, and Brazil.
Argentina's ANMAT published biologics and biosimilar approval guidance in September 2009.
In Mexico, despite the creation of biosimilar guidelines in 2009, the pathway remains impossible to navigate. However, copy-biologics have existed in the country for a number of years, are accepted by patients and physicians alike, and are often considered to be interchangeable with branded products.
Brazil has traditionally been a small market for biologic products given the low rates of reimbursement. However, legislation relating to biosimilars was introduced in 2005.
0
10
20
30
40
50
60
70
Indi
a
China
Argen
tina
Mex
ico EUBra
zil
Egypt
Russia
South
Kor
ea
Bangl
ades
hO
ther
Num
ber
of c
andi
date
s
Approved / Launched biosimilars Approved / Launched copy biologics
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
18
The EU dominates in terms of biosimilar development the EU dominates in terms of product developmentLeading leading markets for biosimilar development
Source: Datamonitor; company-reported information, 2011
The EU leads the field in terms of biosimilar development with 57 candidates (encompassing 32 molecules) – although 20 of which are only in the “planned” stage – reflecting the significant commercial opportunity for biosimilars in this region.
India is the leading country in terms of copy-biologic development, with 40 candidates (eight molecules) undergoing active development, and a further three candidates planned. However, given the limited availability of company-reported development information, the size of the Indian pipeline may be under-represented here.
While only having launched six products to date, South Korea is ranked third in terms of biosimilar development with 29 candidates (13 molecules) currently in development.
0
10
20
30
40
50
60
EUIn
dia
South
Korea US
Japa
n
China
Canad
a
Russia
Taiwan
Brazil
Mex
ico
Latin
Am
erica
unsp
ecifie
d
Nu
mb
er
of
can
did
ate
s
Planned Development Pre-clinical Clinical trials / Pre-approval
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
19
Biosimilar/copy-biologic company analysis (1/4)
The leading companies for biosimilar research and development, 2011
Source: Datamonitor; company-reported information, 2011
The largest copy-biologic producer is India-based Zydus Cadila, reported to have 10 candidates in preclinical development, with a further five at market.
Sandoz is the leading biosimilar developer, with nine candidates in development and four at market. Omnitrope (somatropin; Sandoz) was the first biosimilar to be marketed in the EU, Japan, Australia, and Canada.
0
2
4
6
8
10
12
14
16
Zydus
Cadila
Sandoz
Cipla
Dr R
eddy's
Gen
e Tec
hno Scie
nce
Labor
ator
ios Beta
Bioca
d
Probio
med
Celltrion
Harves
t Moon
Pha
rmace
utica
ls
USV Lim
ited
Bioco
n
Inta
s Biop
harm
aceutic
als
Don
g-A
LG Life
Scie
nces
Relianc
e Life
Scie
nces
Sedico
Shangha
i CP G
uojian P
harm
aceut
ical
Teva
Varifarm
a
Nu
mb
er
of
ca
nd
idat
es
Development Biosimilars Launched Biosimilars Development Copy-biologics Launched Copy-biologics
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
20
Biosimilar/copy-biologic company analysis (2/4)
The leading producers with products launched, 2011
Source: Datamonitor; company-reported information, 2011
All of the top 10 companies in terms of marketed products are copy-biologic manufacturers, reflecting the more relaxed regulatory requirements for the approval of such products in the emerging markets.
The leading companies in terms of launched copy-biologics are Laboratorios Beta and Probiomed, both of which are Latin America-based companies along with Varifarma, Landsteiner Scientific, and Sidus, which also rank among the top 10 companies based on number of marketed copy-biologics. The remaining companies are all India-based, with the exception of Sedico, based in Egypt.
0
2
4
6
8
10
12
Nu
mb
er o
f ca
nd
idat
es
Therapeutic protein Insulin Hormone therapy Blood factor Monoclonal antibody Unknown at present
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
21
Biosimilar/copy-biologic company analysis (3/4)
The leading producers with products in development
Source: Datamonitor; company-reported information, 2011
India-based Cipla is the leading developer with 12 copy-biologics in development (although the nature of these products has not been disclosed), followed by Zydus Cadila – also based in India – which has a range of therapeutic protein and monoclonal antibody (MAb) candidates in development.
In terms of biosimilar development, Japan-based Gene Techno Science leads with 10 biosimilars (MAbs and therapeutic proteins) in development, followed by Sandoz with nine candidates (of which only one – rituximab – has been disclosed).
0
2
4
6
8
10
12
14
Nu
mb
er
of
ca
nd
idat
es
Therapeutic protein Monoclonal antibody Unknown at present Insulin Blood factor
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
22
Biosimilar/copy-biologic company analysis (4/4)
Biosimilar and copy-biologic MAb development activities, 2011
Overall, 30 companies have biosimilar/copy-biologic MAbs in their portfolios, with Reditux (rituximab; Dr. Reddy’s) currently being the only copy-biologic MAb on the market.
BioXpress leads in terms of the number of MAb candidates. However, all 16 are "planned," with no reference to any clinical development having been initiated (BioXpress, 2011).
Celltrion currently has eight MAb candidates, two of which are in clinical development, with five in preclinical development and a further one at the “planned” stage. These eight biosimilars are due to appear in the US, Europe, Australia, Canada, and New Zealand through a marketing agreement between Hospira and Celltrion signed in October 2009 (Berkrot, 2009).
Biosimilar originator company
Total MAb candidates
Lead molecule Stage of lead molecule
BioXpress 16 Various Planned
Celltrion 8 infliximab, trastuzumab Clinical trials/pre-approval
Gene Techno Science 7 Unknown at present Development
Dr. Reddy’s 6 Reditux (rituximab) Approved/launched
Zydus Cadila Total 5 Unknown at present Preclinical
Mabion 4 Unknown at present Development
Biocad 3 bevacizumab, rituximab, trastuzumab
Development
PharmaPraxis 3 Unknown at present Development
Shanghai CP Guojian Pharmaceutical
3 efalizumab, rituximab, trastuzumab
Clinical trials/pre-approval
Aprogen 2 infliximab Clinical trials/pre-approval
Dong-A 2 trastuzumab Preclinical
LG Life Sciences Total 2 adalimumab, infliximab Preclinical
Samsung Biologics 2 rituximab Clinical trials/pre-approval
Others 16 Various Various
the home of Business IntelligenceBiosimilars: Pipeline Trends, HC00149-002, December 2011© Datamonitor
23
Appendix
Ask the analyst• The Strategic Analysis (Healthcare) Knowledge Center Writing team
• Alistair Sinclair asinclair@datamonitor.com
Disclaimer• All Rights Reserved.
• No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher, Datamonitor.
• The facts of this report are believed to be correct at the time of publication but cannot be guaranteed. Please note that the findings, conclusions and recommendations that Datamonitor delivers will be based on information gathered in good faith from both primary and secondary sources, whose accuracy we are not always in a position to guarantee. As such, Datamonitor can accept no liability whatever for actions taken based on any information that may subsequently prove to be incorrect.
Recommended