Biosimilars Overview 18012007 v2

Home
Previous
Next
Last
Biogenerics – Overview and Outlook
www.stratycon.com
© Stratycon Business Solutions Pvt.. Ltd. 2005-07
Contents
Home • Global Biomedicines Industry
– Background
Previous
Previous
– Geographic highlights
– Leading classes and products

Next
Next
– Biologics under development
Last
Last • Biogenerics/ bio-similars/ follow-on biologics
– Background (what products come under this? )
– Accessing regulated markets (Regulatory Status US, EU, Japan)
– Foreseeing Competitive Intensity
– Business Options
– Hurdles & Opportunities
• Concluding Comments
2
Biologics - Background
Home • Global biologics market is estimated to be ~$ 53 billion (excluding

vaccines) constituting ~9% of global pharmaceutical market1
Previous
Previous
• ~125 biologics currently marketed3
Next
Next • The innovation gap for big pharma is filled by biologics (# of NME
approvals for biotech products have exceeded that of big pharma2 )
Last
Last
• >400 biologics in development constituting ~19% of all developments
• By 2010, biologics are expected constitute >15% of global

pharmaceutical market1
Ref:: 1IMS Global Insights 2005; ET Dec 30 2006; 2E&Y Biotech Industry Report 2006; 3
PhRMA Report 2006, IMS-New Markets & Products in 2005; Stratycon Estimates © Stratycon Business Solutions Pvt.. Ltd. 2005-07
Biologics constituted ~9.4% of the total
biopharmaceutical market
Sales Estimates – 2005

Home
Previous
Previous
US, $32.80
Next
Next
Last
Last
EU, $12.18
Global pharma, $549 Other, 52.84

Japan, $3.43
ROW, $4.43
• US is the largest market for biologics with >60% of global biotherapeutic sales, ROW constitutes ~8%
Notes: ROW- Rest of the world; Estimation for 2005
Ref:: Stratycon Estimates; ET Dec 30 2006; IMS Midas 2006; 4

Geographical Highlights
Home
• Current market for biologics ~$ 33 bio.
• Growing at >17% YoY
Previous
Previous • EPO constitute major proportion of sales
Next
Next
• Estimated market size of biologics ~$12 bio

Last
Last
• Biologics growing faster than US at around 20%
• Germany constitutes 1/3rd of 5EU market
• Human insulin, EPO constitute ~19%, 18%
• Estimated biologics market is ~$3.93 bio

• The biologics market has been growing at 7.3%
• EPO constitutes ~23%, followed by mAb (12%)
Ref:: IMS Industry in Figures 2005; JETRO, Japanese Patent Office Survey, Stratycon 5
Estimates © Stratycon Business Solutions Pvt.. Ltd. 2005-07
But the growth of biotech has continuously
outpaced that of pharmaceuticals
Home
30%
Previous
Previous
25%
YoY Growth in %
Next
Next 20%
15%
Last
Last
10%
5%
0%
2000 2001 2002 2003 2004 2005
Pharmaceuticals Biologics
• 23% of total industry growth in 2004 came from biotech products
Ref:: IMS Industry in Figures 2005; Stratycon Estimates 6

# of block buster biologics have significantly
increased over the last 5 years
Home
30
# of Biotech Products with >$1bio sales
Previous
Previous
25 24
Next
Next 20
20
Last
Last
15
11
10
7
6
5
3 3
0
2000 2001 2002 2003 2004 2005 2006
Ref:: IMS Outlook 2005 & Beyond; Product & Company Research by Stratycon 7
..also the number of NBEs approved by FDA till
2005
Home
25
Previous
Previous 21
# of NBEs approved by US FDA
20
20
Next
Next
15
15
13
12
Last
Last
10
5 4
2
0
2001 2002 2003 2004 2005 2006 2007 till Nov
30
Ref:: Ronald A. Rader; Record Number of Biopharmaceuticals Approved: 2005 Was a 8

Record-Setting Year; BioPlan Associates 2006, FDA Approval History (Accessed Dec 07) © Stratycon Business Solutions Pvt.. Ltd. 2005-07
Projected biologics market by geography
(2010)
Projected Biologics Sales
Home
70 66.45
Previous
Previous
60
Biologics Market in $bio.
Next
Next
50
Last
Last 40
30
24.92
20
11.08
9.55
10
0
US EU Japan ROW
Ref:: Stratycon Estimates 9

Home
Leading Classes &

Previous
Previous
Next
Next
Products
Last
Last
Erythropoietin, TNF, insulin analogs and cancer antibodies are
leading biologic categories (excluding vaccines)
Neulasta/Neupogen G-CSF from Amgen is the leading biologic with
2005 global sales of $3.5 bio.
Top 10 biologics constitute 49.5% of total biologics market
10
Erythropoietin is the leading class of biologic
constituting ~22% of biologic market (excl. vaccines)
Home
12.0 Erythropoietins
10.9
Previous
Previous TNF
10.0
Insulin & analogs
2005 Global Sales $ bio.
Next
Cancer Antibodies
Next
8.0 7.6
7.2 Interferon Beta
6.8
G-CSF
Last
Last
6.0
Human Growth Hormone
Rec. Coagulation Factors

3.8 3.8
4.0
Interferon Alpha
2.3 2.2 2.1
Enzyme Replacement
2.0
1.3 1.1
1.0 Antiviral Antibody
Follicle Stimulating Hormones

0.0
11
7 of top 10 products have annual global sales of > $ 2
bio. (2005)
Home
4.0
Neulasta/NEUPOGEN
3.5
Previous
Previous 3.5 3.33 3.32 3.27 MabThera/Rituxan
3.0 Procrit/Eprex
2005 Global Sales $ bio.
Next
Next 2.57 2.54 2.46 Aranesp
2.5
Enbrel
Last
Last 2.0 1.81
1.72
Remicade
1.54
1.5
Epogen
1.0 NeoRecormon,Epogin
Herceptin
0.5
Avonex
0.0
12
Leading Biotech Products
2005 ww Sales
Product Compound Company Growth (Y0Y) %
Home ($ bio.)*
NEULASTA /NEUPOGEN Peg/filgrastim Amgen 3.50 31.5%

Previous
Previous
MABTHERA/ RITUXAN rituximab Roche/Genentech 3.33 22.0%
PROCRIT/ EPREX epoetin alfa J&J 3.32 -7.0%

Next
Next
ARANESP darbepoietin alfa Amgen 3.27 32.0%
ENBREL etanercept Amgen 2.57 42.0%

Last
Last
REMICADE infliximab J&J 2.54 18.0%
EPOGEN epoetin Alfa Amgen 2.46 -6.0%
NEORECORMON,
epoetin beta Roche 1.81 8.0%
EPOGIN
HERCEPTIN trastuzumab Roche 1.72 48.0%
AVONEX interferon beta-1a Biogen Idec 1.54 8.90%
Total of Top 10 26.07
Notes: *World Wide Sales in US $ billion

13
4 of $2 + bio. biologics are growing at more than 20%
Y0Y
Top 10 biologics - 2005

Home 4.0
Neulasta/Neupogen
3.5 MabThera/Rituxan
Procrit/Eprex Aranesp
Previous
Previous
2005 Global Sales in $ bio.
3.0
Epogen Remicade Enbrel

2.5
Next
Next
2.0
NeoRecormon,Epogin
Last
Last Herceptin
1.5 Avonex
1.0
0.5
0.0
-10% 0% 10% 20% 30% 40% 50% 60%
YoY Growth
• The Strongest growth was observed for Avastin - bevacizumab (+141%), Humira (+64%) and Herceptin (+48%)
Note: Avastin & Humira doesn’t feature in top 10 biologics
14
Home
Previous
Previous
Next
Next
Pipeline of Biologics
Last
Last
~19% of all drugs under development are biologics, with mAbs

accounting for ~34% of all biologics being developed.
~46% of biologics in clinical stages are being developed for cancer.
In 2010, ~50% of all new approved pharmaceuticals will be biologics.
15
Monoclonal antibodies, gene therapy are constitute
major proportion of biologic pipeline apart from
vaccines
# of Biologic in Development by Category
Home
62
Others
Previous
Previous 8
Interleukins
9
Immune based therapy
Growth Factors 16
Next
Next
Interferons 18
Antisense 20
Last
Last Cellular therapy 21
Recombinant Hormones/Proteins 43
Gene Therapy 46
Vaccines 62
mAbs
160
0 50 100 150 200
• ~19% of all pipelines are biotech products
Notes: Could include pre-clinical molecules hence total is more than
Ref:: PhRMA Report 2006; 16

Biologic pipeline has major focus on
cancer, infectious diseases, HIV/AIDS
# of Biologic in Development by Disease Segment
Home
18
Other
4
Previous
Previous Transplantation
4
Growth Disorders
6
Eye Conditions
Skin Disorders
7
Next
Next
Blood Disorders 10
Respiratory Disorders 13
Digestive 14
Last
Last
Diabetes/Related 15
Neurologic Disorders 17
Cardiovascular 22
AIDS/HIV Related 22
Autoimmune 44
Infectious Diseases
50
Cancer/Related
210
0 50 100 150 200 250
Ref:: PhRMA Report 2006 17

Home
Previous
Previous
Next
Next
Biosimilars
Last
Last
Current global market of biosimilars is estimated to be less than

$100 mio. Regulated markets are taking the next step for
biosimilars. ROW countries could act as a launch pad taking
products subsequently to regulated markets.
18
Biosimilars - Background
Home • The current global biosimilars market is estimated to be ~ $100

mio.
Previous
Previous
• With the advent of EMEA’s progress in drafting guidelines, the
scenarios is expected to be bright
Next
Next
• By 2011, biologics worth $18 bio. annual sales are expected to
lose patent protection in developed pharmaceutical markets
Last
Last
• The global biogenerics market opportunity is estimated to be
worth >$2 bio by 2008, (but it could be to the tune of >$5 bio.
considering possible market expansion)
– EPO, CSFs and hGHs are expected to account for the majority of the
biosimilar sales
• US still lags behind entangled with a number of debates and
influencing stake holders
Ref:: The Future of Biogenerics- PharmaVoice – May 2005; Chemical & Engineering News - 19
June 6, 2005; F&S Articles, Stratycon Analysis © Stratycon Business Solutions Pvt.. Ltd. 2005-07
Selected biologics with expired patent
Product Compound Company Expired

Home
Neupogen G-CSF Amgen 2006

Previous
Previous
Novolin Human Insulin NovoNordisk 2005
Next
Next
Protropin Growth hormone Genetech 2005
Activase t-PA Genentech/BI 2005
Last
Last
Epogen, Procrit EPO-α Amgen/J&J/Sankyo 2004
Nutropin Growth Hormone Genentech 2003
Humatrope Growth Hormone Eli Lilly 2003
Avonex Interferon b1a Biogen 2003
Intron A Interferon a2b Schering Plough 2002
Humulin Human Insulin Eli Lilly 2001
20
Home
Previous
Previous
Next
Next
Biosimilars - Regulatory
Last
Last
EU has guidelines in place for approval of biosimilars, US and Japan

lag behind in the process.
21
EU has defined regulatory requirements
for biosimilars
Home • EMEA has developed guidelines for approval of biosimilars

– Draft guidelines, including specific clinical and non-clinical data requirements for four
product types:
Previous
Previous • Recombinant insulin, human growth factor, erythropoietin and CSFs
• The Committee for Medicinal Products for Human Use (CHMP) issues specific
Next
Next guidelines on case by case
– Comparability studies are required to substantiate evidence for safety, efficacy and quality
– Advised to approach EMEA for detailed case by case basis guidance on studies required to
Last
Last
be conducted
– Product-class specific guidance documents on pre-clinical and clinical studies to be
conducted for the development of biosimilars will be progressively available
– The authority for marketing approval of a biosimilar lies with EC
• Omnitrope is the first biosimilar to be approved in EU, which was earlier approved
in Australia by TGA. Biopartner’s Valtropin is approved and α interferon is under
review
• Note: EU has constituted 10 year data exclusivity period for all pharmaceutical innovators.
(this prevents a patent challenger to use innovators safety & efficacy data)
Ref: EMEA (Accessed Jan 07)

22
US is still in the process of developing
guidelines for biosimilars
Home • Currently there is no clear guidelines and authority for approval of

biosimilars
Previous
Previous • Drugs generally covered by Federal Drug & Cosmetic Act, and biologics
approved under Public Health and Safety Act
Next
Next
– Most of the Biologics are approved through BLA
– Some early biologics, such as human growth hormone (hGH), insulin, and
conjugated estrogens, were approved as drugs by FDA under the FD&C Act
Last
Last
– ANDAs could be applicable for these products, subject to FDA resolution of the
scientific and other issues involved.
• Guidelines for approval of biosimilars currently not defined
– No equivalent of ANDA under PH&S act for approval of follow on biologics
(biosimilars)
– The congress and the FDA are considering various scientific and legal issues
surrounding follow-on biologics, to define a regulatory process for follow on
biologics
• Biosimilar Omnitrope is approved in US
Ref: FDA
23
US - Some products under NDA may be approved
without new ‘follow on biologics’ legislation!
Home Approved Through NDA Approved Through BLA
Previous
Previous
Insulin Interferons
Growth Hormone, FSH, LH,

Next
Next tPA
hCG, TSH
Calcitonin EPO
Last
Last
PTH mAb
Imigucerase Enzymes
Aprotinin
Hyaluronidase
Ref: FDA
24
Japan – PDMA – Office of biologics
evaluates generic biologics
Home • Currently there is no guidelines for approval of biosimilars

• CPAC & MHFW are authorities for pharmaceuticals
Previous
Previous
– Central Pharmaceutical Affairs Council evaluates and makes the
recommendation & the Ministry of Health and Family Welfare makes the
decision on approval of drugs, biologics
Next
Next
• PMDA (Pharmaceutical & Medical Devices Agency) – Office of Biologics

Last
Last – Provides consultations concerning the clinical trials of new drugs and medical
devices
– Has ‘Office of biologics’ for handling biotech medicines including generic
biologicals
• Use of foreign clinical data is very limited while approval of new
medicines, and less likely that glycosolated proteins will be recognised as
generics
Ref: MHW, JPMA Report 2006

25
Home
Previous
Previous
Next
Next
Last
Last Biosimilars –
Competitive Intensity
26
Foreseeing Competitive Intensity
Home • How big is the market?
Previous
Previous
Next
Next
• How complex is the manufacturing process?
Last
Last
• Will the regulatory approval be through a relatively abbreviated

process?
27
Biosimilars – Evaluating Probable
Competitive Intensity
Size of bubble: Innovator Brand Sales -2005 ($ bio.)
7
Home
Neupogen
Previous
Previous 6
Retuxan
Next
Next 5
Procrit/Eprex
Ease of Mnf. Score
Last
Last Enbrel
4
Humulin
3
Avastin
2
Genotropin
1
1 2 3 4 5 6 7
Reg. Simplicity
Portfolio Development Path (considering market size)
Ref: Stratycon Analysis – Draft

28
Leading Generic Companies & their
biosimilar portfolio
Interfero
Company EPO CSF Insulin HGH tPA mAb Total
Home n
Teva/Sicor/BTG D M M M 4
Previous
Previous
Sandoz M 1
Pliva (+Mayne) M D M 3
Stada D D D 3
Next
Next
BioPartners/LG
M M M M M 5
LS
BioGeneriX D D 2
Last
Last
GeneMedix D M D D 4
Dragon M 1
Biocon D M M D D D D 7
Scino Pharma D D D D D 5
SciGen M M M D D 5
Wockhardt M D M D 4
DRL D M D 3
Shanta Biotech M D M M D 5
Total 11 9 6 7 9 3 6 52
Total (M) 5 5 5 4 4 1 0 24
Note: List is not complete, M: Marketed, D: Developing
Ref: News releases, company research 29

Biogenerics – Probable Competitive Outcomes
under regulatory uncertainty
Biosimilars Regulatory
Process in Question
Home
Doesn’t Require large Requires large

Previous
Previous Clinical Tests Clinical Trials
Next
Next Less More
Time to Time to
Market Market
Last
Last Higher
Higher Price Lower Price Lower Competitive
Competitive
Differential Differential Intensity
Intensity
Authorized Bio- Limited Change in

similar well in Expanded Demand Next Gen
Demand
advance Biologics
Price & Competitive

Equilibrium Incremental product
Next Gen
Focus on Next Innovations
Biologics
Focus on Next Potential Potential Biologic
Biologic going off patent – going off patent?
Process Innovations
!get it first to the market
for cost cutting
Likely Strategies by Innovator

30
Constraints & Drivers
Home
CONSTRAINTS DRIVERS
Previous
Previous
• Regulatory • Biologics segment size & growth
– No clear cut regulatory mechanism in – Biologics performance exceeds that
US, Japan of overall market
Next
Next
• Technological – Biologics worth $18 bio. Will go off
patent by 2011
– Manufacturing complexity
• Increasing pressure to reduce
Last
Last – High setup & manufacturing costs
healthcare expenditure
– Higher cost to prove comparability
– Evolving regulatory mechanisms to
• Market Factors recognise biosimilars (EU, Australia)
– Next generation biologics • Semi/unregulated markets as launch
– Limited discounting ability pad
(discounting in the range 25% to
30%) • Generic majors like Teva, Maine,
Pliva developing biosimilar
– Authorised generics/price cuts
capabilities through partnerships as
– Gaining acceptance by clinicians well
(brand based competition)
31
Business Options – Step by step
approach?
Home
Japan!
Previous
Previous
Next
Next US
Last
Last
EU
Unregulated Markets
32
Analyzing business options
Home
Market yourself?
Authorized
Previous
Previous Generics?
Selective partnering?
Next
Next
Have/ Can build
Complete partnering?
Last
Last
Marketing & Regulatory

Market in Question competency?
Doesn’t have/can’t build Out-license?
33
Comments
Home • Biologics approved through NDA and easy to manufacture could be the
first targets for generic manufacturers
Previous
Previous • Semi/unregulated markets could act as launch pad for biosimilars and
could be beneficial in accelerated approvals in regulated markets (once
the guidelines are in place)
Next
Next
• Big generic companies like Teva, Sandoz, Pliva have significant focus
on biosimilars and have access to market and marketing resources
Last
Last
• Medium size/ biotechs from developing world are increasingly following
collaborative models to accelerate commercialization of their biologics
• Biologic innovators will move forward with the next-generation
biologics trying to make up for revenue loss due to biosimilars
– This is facilitated by biotech innovators bridging the innovation gap of big
pharmaceuticals
34
Home
Previous
Previous
Next
Next
Back-up
Last
Last
35
Global Pharmaceutical Market Sales
Global Pharmaceuticals Sales 2005
Home
Previous
Previous
Next
Next
2005
$265.70 169.5 60.3 46.4 24
Last
Last
$0.00 $100.00 $200.00 $300.00 $400.00 $500.00 $600.00
North America Europe Japan Asia, Africa and Australia Latin America
Ref:: 1IMS Industry in Figures - 2005 36

Biopharmaceuticals’ share of global
prescription sales
Home
Previous
Previous
Next
Next
Last
Last
Ref:: IMS - 2004 37

Generic Pharmaceutical Sales in US
Home
25 54%
53.3%
Previous
Previous
52%
20
Generic Sales in US - $ bio
Next
Next 50.5%
50%
% Generic Rx
15
Last
Last 48.1% 48%
47.4%
10 46.6%
46.5%
46%
5
44%
11 13 14.3 16 18 22
0 42%
2000 2001 2002 2003 2004 2005
Ref:: GPhA 38
Leading products Next 10 (rank 10 to 20)
Next 10 biologics - 2005

Home 1.5
1.4 Humira
Avastin
Previous
Previous
1.3
Rebif
Neupogen
2005 Global Sales in $ bio.
Lantus
1.2 Humalog
Next
Next
Pegasys
1.1 Synagis
Last
Last
1.0 Betaferon
Humulin
0.9
0.8
0.7
0.6
-20% 0% 20% 40% 60% 80% 100% 120% 140% 160%
YoY Growth
39
Analysis of approval pattern of biologics
by expression system & source (US)
Products by Expression System
Home
45
40 0 Natural Extract
35
# of Biologics
1
Mammalian cell
Previous
Previous 30 8 26 culture
25 4 Yeast
20
10
15 2 Bacteria
Next
Next
10
13
5 11
None (Synthetic)
0 0
Last
Last NDA BLA
Products by Source
45
40
native DNA
35 2
# of Biologics
30
rDNA
25
21 41
20
Synthetic
15
10
5 11
0
NDA BLA
Ref: Biopharm Intl;

40
Evaluating ease of manufacturing
Home
Expression System
Previous
Previous
Next
Next
Last
Last
Source (Natural DNA/

Chemical Modification
rDNA/ synthetic)
41

Biosimilars Overview 18012007 v2

Diunggah oleh

Informasi Dokumen

Hak Cipta

Format Tersedia

Bagikan dokumen Ini

Bagikan atau Tanam Dokumen

Opsi Berbagi

Apakah menurut Anda dokumen ini bermanfaat?

Apakah konten ini tidak pantas?

Hak Cipta:

Format Tersedia

Biosimilars Overview 18012007 v2

Diunggah oleh

Hak Cipta:

Format Tersedia

Home

Biogenerics – Overview and Outlook

Home • Global Biomedicines Industry

– Leading classes and products

– Biologics under development

– Background (what products come under this? )

– Accessing regulated markets (Regulatory Status US, EU, Japan)

– Foreseeing Competitive Intensity

– Hurdles & Opportunities

Home • Global biologics market is estimated to be ~$ 53 billion (excluding

• By 2010, biologics are expected constitute >15% of global

Sales Estimates – 2005

Global pharma, $549 Other, 52.84

Notes: ROW- Rest of the world; Estimation for 2005

Ref:: Stratycon Estimates; ET Dec 30 2006; IMS Midas 2006; 4

• Estimated market size of biologics ~$12 bio

• Estimated biologics market is ~$3.93 bio

• 23% of total industry growth in 2004 came from biotech products

Ref:: IMS Industry in Figures 2005; Stratycon Estimates 6

Ref:: Ronald A. Rader; Record Number of Biopharmaceuticals Approved: 2005 Was a 8

Ref:: Stratycon Estimates 9

Leading Classes &

Rec. Coagulation Factors

Follicle Stimulating Hormones

NEULASTA /NEUPOGEN Peg/filgrastim Amgen 3.50 31.5%

PROCRIT/ EPREX epoetin alfa J&J 3.32 -7.0%

ENBREL etanercept Amgen 2.57 42.0%

REMICADE infliximab J&J 2.54 18.0%

EPOGEN epoetin Alfa Amgen 2.46 -6.0%

HERCEPTIN trastuzumab Roche 1.72 48.0%

AVONEX interferon beta-1a Biogen Idec 1.54 8.90%

Total of Top 10 26.07

Notes: *World Wide Sales in US $ billion

Top 10 biologics - 2005

Epogen Remicade Enbrel

Note: Avastin & Humira doesn’t feature in top 10 biologics

~19% of all drugs under development are biologics, with mAbs

0 50 100 150 200

• ~19% of all pipelines are biotech products

Notes: Could include pre-clinical molecules hence total is more than

Ref:: PhRMA Report 2006; 16

0 50 100 150 200 250

Ref:: PhRMA Report 2006 17

Current global market of biosimilars is estimated to be less than

Home • The current global biosimilars market is estimated to be ~ $100

Product Compound Company Expired

Neupogen G-CSF Amgen 2006

Activase t-PA Genentech/BI 2005

Nutropin Growth Hormone Genentech 2003

Humatrope Growth Hormone Eli Lilly 2003

Avonex Interferon b1a Biogen 2003

Intron A Interferon a2b Schering Plough 2002

Humulin Human Insulin Eli Lilly 2001

EU has guidelines in place for approval of biosimilars, US and Japan

Home • EMEA has developed guidelines for approval of biosimilars

– The authority for marketing approval of a biosimilar lies with EC

Ref: EMEA (Accessed Jan 07)

Home • Currently there is no clear guidelines and authority for approval of

Home Approved Through NDA Approved Through BLA

Growth Hormone, FSH, LH,

Home • Currently there is no guidelines for approval of biosimilars

• PMDA (Pharmaceutical & Medical Devices Agency) – Office of Biologics

Ref: MHW, JPMA Report 2006

Home • How big is the market?