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World Preview 2016 Beyond the Patent Cliff

June 2011

Welcome to the EvaluatePharma World Preview 2016


The fourth edition of EvaluatePharmas World Preview brings together many of our analyses to provide a top level insight, from the worlds financial markets, into the expected performance of the industry between now and 2016. Based on EvaluatePharmas coverage of the worlds leading 3,000 pharmaceutical and biotech companies, the World Preview highlights trends in prescription drug sales, patent risk, R&D spend, global brand sales and market performance by therapy area. Also included in the report is a brief review of 2010 performance. In this years edition of the World Preview we have updated the analysis of the market to 2016 and focused on how the forecast to 2016 has changed compared to the last edition in May 2010.

About EvaluatePharma
Since 1998 EvaluatePharma has been providing senior decision makers within the pharmaceutical industry with an essential service that models the sector from the viewpoint of the worlds financial markets. EvaluatePharmas forward looking view of the market is hugely influential as it displays the consensus of expectations, which influence company stock market valuations. The forecasts of equity analysts reveal their perspectives on individual company performance, industry trends and the macro economic environment. EvaluatePharma has captured the consensus forecasts of equity analysts and seamlessly integrated them with the historic results, as reported by companies. From this comprehensive view of the industry, its past and expected future performance emerges and can be analysed using EvaluatePharma. Analyses range from total market trends and therapeutic overviews to individual company performance and product progress. Whatever your view on the future of the industry, EvaluatePharma can help you find value in the pharma and biotech sector. To find out more about this report and EvaluatePharma services contact us: North America: Debbie Paul Tel: 1-617-573-9453 Email: debbiep@evaluatepharma.com Rest of the World: Will Hau Tel: +44 (0)20 7377 0800 Email: willh@evaluatepharma.com

General Enquiries: pharmainfo@evaluatepharma.com


Disclaimer This report may not be relent, resold, hired out or otherwise disposed of by way of trade in any form of binding or cover other than that in which it is published, without the prior consent of EvaluatePharma Ltd. While all reasonable steps have been taken to ensure that the data presented are accurate, EvaluatePharma Ltd cannot accept responsibility for errors or omissions. Neither does EvaluatePharma Ltd warrant the accuracy, merchantability or fitness of use for a particular purpose of the data.

World Preview to 2016

June 2011

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

EvaluatePharma Foreword:
Last years edition of the World Preview highlighted that prescription drug sales were forecast to increase by 2.9% per year between 2010 and 2016. In this edition, we can report an upward revision in growth to 4.0% per year between 2010 and 2016. The uplift can be attributed to an upward revision in consensus product forecasts (see page 19) due to favourable news events (page 26), the continuing weakness in the dollar vs. major currencies and a general improvement in sentiment over the last 12 months. Does this signal anything of substance? Despite the upward revision, prescription sales growth is still forecast to lag world economic growth, predicted by the IMF to be 4.4% per year over 2011 and 2012. Underlying this is a two speed world, with developed economies growing at 2.4% and emerging economies growing at 6.5% per year over the period. In a business world increasingly obsessed with emerging markets, it is often overlooked that the ultimate prize for global majors is to sell innovative patented products to the wealthy sub-populations in emerging markets who can afford private healthcare and to convince governments to pay for patented products, rather than selling generic drugs listed on reimbursement lists. Struggling global majors may talk-up the Chinese market, but it cannot be viewed as a substitute for innovation. The shift in the pharmaceutical industrys focus from the dominant US market towards emerging markets is a symptom of patent expirations coupled with poor R&D productivity, rather than any fundamental economic weakness in the US market. GlaxoSmithKlines decline, to be outside of the worlds Top 5 biggest sellers of prescription medicines in 2010 (page 22), is a prime example. Its failure to replace ageing blockbusters has seen its US pharmaceutical sales decline from $19.1bn in 2006 to $11.8bn in 2010, despite spending more than $30bn on R&D over the same period. On R&D productivity, 2010 did register a bumper year for new drug approvals in the US in terms of quality. Despite the number of new drugs approved declining 24% in 2010 to 26, the quality of the approved products (based on US sales 5 years post-launch) more than doubled to $13.3bn (page 12), easily the best year since 2004 (when Avastin was approved). This years increase in quality, coupled with flat (declining in real terms) industry R&D investment over the last 3 years, is a positive step towards rebalancing R&D output to investment. The imbalance remains huge with the average Net Present Value (NPV) of new products averaging $70bn per year between 2008-10, versus R&D investment at $127bn per year. The Industry as a whole is not yet generating a return on R&D investment. Even if all R&D was successful it is unlikely governments would be capable of reimbursing all new products. It is telling that when Pfizer announced the removal of $1.5bn from its 2012 R&D spend, its stock price rose 5%. In an age of austerity who will be next to wield the axe to their R&D budget? In terms of patent expiries 2011 and 2012 are forecast to be the worst years, with $54bn of sales set to be lost. With small molecule patent expiries relatively priced-in and given a more balanced R&D output to investment, the financial markets may start to re-evaluate global majors as having a more positive long term growth prospect beyond the patent cliff. The analysis we present here is a snapshot of an evolving picture so please view it as such. But whatever the outlook, EvaluatePharma is there to help you find value in the pharma and biotech sector. Anthony Raeside, Head of Research
World Preview to 2016 June 2011

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

EvaluatePharma World Preview 2016 Analysis Highlights

2016 forecasts for the top 50 products have increased by $21.7bn (+13% upgrade) since April 2010; Worldwide prescription drug sales total $853bn in 2016; Since April 2010 growth revised up from 2.9% to 4.0% (CAGR) over 2010 2016; Over $255bn of sales at risk from patent expirations in 2011-16; Humira world's largest selling product in 2016; Pfizer, Novartis and Sanofi competing for top spot in 2016; Biotech products fail to overtake small molecule sales within top 100 drugs by 2016; Global pharmaceutical R&D spend returns to growth in 2010 following unprecedented decline in 2009; still over investment; Pfizers 2016 R&D spend revised down by $1.2bn since April 2010; Anti-coagulants set to record highest growth of major therapy categories to 2016; Best year for NME approvals since 2004 as sales potential doubles; number of new drugs approved down 24%; GSK falls out of top 5 in 2010; first time since late 1980s; Teva continues to dominate generic drug market in 2010; Roches company value slumps in 2010 due to setbacks to Avastin and taspoglutide; Novo Nordisks share price soars in 2010 following series of positive events within anti-diabetic business

World Preview to 2016

June 2011

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

Table of Contents

Worldwide Prescription Drug Sales (2002-16) Worldwide Prescription Drug Sales in 2016: Top 20 Companies Worldwide Prescription & OTC Sales by Technology (2002-16) Top 20 Most Valuable R&D Projects (Ranked by Net Present Value) Worldwide R&D Spend by Pharma & Biotech Companies (2002-2016) Pharmaceutical R&D Spend in 2016: Top 20 Companies FDA New Drug Approval Analysis (NMEs & Biologicals): 1997 to 2010 Worldwide Rx & OTC Sales by Therapy Area in 2016 Oncology Market to 2016 Anti-Diabetic Market to 2016 Anti-Rheumatics Market to 2016 Vaccine Market to 2016 Anti-Virals Market to 2016 2016: Top 50 Selling Products in the World 2016: Top 50 Selling Products in the USA Worldwide Rx & OTC Sales by Therapy Area in 2010 Worldwide Prescription Drug Sales in 2010 Worldwide Generic Drug Sales in 2010 M&A Analysis: 2006 to 2010 Venture Financing Analysis: 2006 to 2010
New Analysis New Analysis New Analysis

6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33

Key Product Events Positively Impacting Shareholder Value in 2010

Key Product Events Negatively Impacting Shareholder Value in 2010 Enterprise Value Analysis: 2009 to 2010 Net Income in 2010: Top 20 Companies Net Income Margin in 2010: Top 20 Companies 2010: Top 50 Selling Products in the World 2010: Top 50 Selling Products in the USA About EvaluatePharma

World Preview to 2016

June 2011

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

Worldwide Prescription Drug Sales (2002-16)


Worldwide Prescription Drug Sales Forecast to Grow by 4.0% (CAGR) to $853bn by 2016 EvaluatePharma finds that the market for prescription drugs, based on the consensus forecast for the leading 500 pharmaceutical and biotechnology companies, will grow by 4.0% per year (CAGR) between 2010 and 2016 to $853bn. This represents an upward revision on industry growth, given the comparable 2.9% growth per year predicted in last year's edition of the World Preview. This upward revision can be attributed to a number of positive event outcomes (see page 26), which led to product forecasts adding $39bn in 2016 (page 19), and the continuing weakness in the dollar, which raised the currency translated value of sales outside of the USA. The key dynamic limiting future growth from returning to the high single digit level experienced prior to 2009 is the sharp increase in sales at risk from patent expirations, which sees $255bn of sales at risk between 2011 and 2016 ($139bn predicted to be lost). Worldwide Total Prescription Drug Sales 2002-16 Source: EvaluatePharma (25 MAY 2011)
WW Prescription Sales ($bn) 900 800 700 600 500 400

+15% +12% +10% +8% 454 406 354 +3% +3% 493 +10% +9% 539 +8% 592 640 656 675

+16.0%
+4.0% CAGR 2010-16

711

730

757

791

820

853

+14.0% +12.0% +10.0% +8.0%

+5% +4% +3%

300 200 100 0

+5% +4%

+6.0%

+4%
+4.0% +2.0% +0.0%

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

Worldwide Sales At Risk from Patent Expiration 2002-16


WW Sales ($bn)
70
Total Sales at Risk

2016

10%
Expected Sales Lost % of Rx Market At Risk

60 50 40 30 20 10 0 2002 13 9 4%

9% 63 6% 41 4% 33 32 21 24 19 22 5% 41 47 6% 4%

9% 8% 7% 6% 5% 31 4% 3% 20 2% 1% 0%

5% 4% 3% 2% 18 7 2003 8 13 12 2004 11 2005 19 13 2006 2007 4% 4% 3% 4% 26 21 20 21 13 2008 10 2009 13 2010 33

2011

2012

2013

2014

2015

Patent Analysis: 'Total Sales at Risk' represent the worldwide product sales in the year prior to patent expiry but allocated to the year of expiry. E.g. Lipitor had sales of $10.7bn in 2010, this is shown above as 'At Risk' in 2011. Worldwide Prescription Drug Sales (2002-16)
Swine Flu Contribution* 1.0 8.4 5.8 2.0 1.9 2.0 2.0 2.0 2.0

WW Prescription Sales ($bn) Year 2002 2003 2004 2005 Prescription (Rx) Growth per Year Change vs. April 2010**
354 +9.6% 406 454 493 +8.4% +14.8% +11.8%

2006
539 +9.4%

2007
592 +10.0%

2008
640 +8.0%

2009
656 +2.5% +12

2010
675 +2.9% +13

2011
711 +5.3% +28

2012
730 +2.7% +31

2013
757 +3.7% +34

2014
791 +4.5% +45

2016

2015
820 +3.7% +54

+4.0% +68

Source: EvaluatePharma (25 MAY 2011) CAGR 10-16 +4.0% Note: Industry sales based on Top 500 pharmaceutical and biotech companies. Sales to 2010 based on company reported sales data. Sales forecasts to 2016 based on a consensus of leading equity analysts' estimates for company product sales and segmental sales. *Swine Flu products include vaccines and influenza treatments Tamiflu and Relenza **EvaluatePharma expanded company coverage added $12bn to 2009 vs. April 2010.

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

% At Risk
2016
853

Expected Key Patent Expiries in 2012: Plavix (SNY/ BMS) Seroquel (AZN), Diovan (NVS), Singulair (MRK), Actos (TAK), Lexapro (FRX) & Viagra (PFE).

WW Sales Growth %

Worldwide Prescription Drug Sales in 2016: Top 20 Companies


Pfizer, Sanofi and Novartis Contesting Top Spot in 2016 EvaluatePharma finds that Pfizer, Sanofi and Novartis will be competing for the position of largest pharma company in the world in 2016 (based on prescription drug sales); all predicted to have prescription sales in the region of $50bn in 2016. Novo Nordisk is set to climb 5 ranking positions to 12th with sales growing 9% per year to $18.4bn in 2016, due to strong insulin franchise sales (including the potential new longer-acting insulin product, Degludec) and growth of its new GLP-1 agonist, Victoza. Teva is forecast to climb 4 ranking positions to number 9 in the world, partly aided by the acquisition of German generic company ratiopharm in 2010. Eli Lilly is set to plunge 6 ranking positions to 14th in 2016 following patent expiration of Zyprexa in 2011 and Cymbalta in 2013, which leads to a 4% decline per year in prescription sales between 2010 and 2016. WW Prescription Drug Sales in 2016: Top 10 Companies Source: EvaluatePharma (25 MAY 2011)
WW Prescription Sales ($bn) 60 50 40 30 20 10
Sales ($bn) CAGR 2010-16 (%) Ranking Chg. 2010-16

51.2
-1%

50.2
+5%

49.7
+3%

45.0
+4%

43.6
+3%

42.3
+1%

27.0
-3%

24.4
+3%

23.9
+9%

21.9
+1%

(-)
0 Pfizer

+2
Sanofi

-1
Novartis

+2
GlaxoSmithKline

(-)
Roche

-3
Merck & Co

(-)
AstraZeneca

+2
Abbott Laboratories

+4
Teva Pharmaceutical

-1
Johnson & Johnson

WW Prescription Drug Sales (2010/16): Top 20 Companies & Total Market


Company Pfizer Sanofi Novartis GlaxoSmithKline Roche Merck & Co AstraZeneca Abbott Laboratories Teva Pharmaceutical Johnson & Johnson Bayer Novo Nordisk Bristol-Myers Squibb Eli Lilly Amgen Takeda Boehringer Ingelheim Daiichi Sankyo Astellas Pharma Baxter International Total Top 20 Other Total WW Prescription Sales ($bn) 2010 2016 % CAGR 10-16
54.1 36.6 41.4 35.6 35.6 40.4 32.1 19.9 14.5 20.7 14.2 10.8 15.5 20.8 14.7 12.6 12.6 10.8 10.3 8.1 461.1 213.7 674.8 51.2 50.2 49.7 45.0 43.6 42.3 27.0 24.4 23.9 21.9 18.8 18.4 17.5 16.8 15.3 15.0 13.7 12.8 11.9 11.0 530.3 322.5 852.8 -1% +5% +3% +4% +3% +1% -3% +3% +9% +1% +5% +9% +2% -4% +1% +3% +1% +3% +2% +5% +2% +6% +3%

2016 Change vs. Apr-2010


+4.0 +11.2 +2.6 +6.3 -0.3 -4.0 +4.9 -1.7 +3.1 -2.9 +1.3 +3.6 +1.8 -0.3 -3.3 +2.9 -0.8 +1.6 +1.3 -1.1 +30.4 +37.8 +68.2

2010
8.0% 5.4% 6.1% 5.3% 5.3% 6.0% 4.7% 2.9% 2.1% 3.1% 2.1% 1.6% 2.3% 3.1% 2.2% 1.9% 1.9% 1.6% 1.5% 1.2%

WW Market Share 2016 Chg. (+/-)


6.0% 5.9% 5.8% 5.3% 5.1% 5.0% 3.2% 2.9% 2.8% 2.6% 2.2% 2.2% 2.0% 2.0% 1.8% 1.8% 1.6% 1.5% 1.4% 1.3% 62.2% 37.8% 100.0% -2.0% +0.5% -0.3% +0.0% -0.2% -1.0% -1.6% -0.1% +0.7% -0.5% +0.1% +0.5% -0.3% -1.1% -0.4% -0.1% -0.3% -0.1% -0.1% +0.1% -6.2%

Rank Chg. (+/-)


+2 -1 +2 -3 +2 +4 -1 +3 +5 -2 -6 -3 -2 -1 -1

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

68.3% 31.7% 100.0%

Source: EvaluatePharma (25 MAY 2011) Note: Prescription drug sales include generic drug sales. Excludes alliance revenue and royalties where possible.

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

Worldwide Prescription & OTC Sales by Technology (2002-16)


Biotech Products Fail to Overtake Small Molecule Sales within Top 100 Drugs by 2016 EvaluatePharma finds that the percentage of sales from biotechnology products (bioengineered vaccines + biologics), within the world's top 100 drugs, is set to increase from 33% in 2010 to 45% by 2016. This is a downward revision on the 48% contribution forecast in April 2010. In the broader market, sales from biotechnology products are set to capture 21% of the world pharmaceutical market by 2016, versus its current share of 18% in 2010. The total value of biotechnology sales is set to grow 48% between 2010 and 2016 from $130bn to $192bn. Percentage of Worldwide Rx & OTC Pharmaceutical Sales from Biotech vs. Conventional Technology Source: EvaluatePharma (25 MAY 2011)
Technology % of Rx & OTC Sales 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
85 % 15 % Biotech Within Top 100 Products Biotechnology's rapid increase in share within Top 100 products: 2002 (15%), 2010 (33%) & 2016 (45%) 33 % Biotechnology Conventional/ Unclassified

90%

89%

88%

87%

86%

85%

84%

83%

82%

81%

80%

79%

79%

79%

79%

67 %

55 %

45 %

10%

11%

12%

13%

14%

15%

16%

17%

18%

19%

20%

21%

21%

21%

21%

2016 Split: Biotech: n=41 (avg. $2.78bn) Conv.: n=59 (avg. $2.35bn)

2013

2014

2015

Worldwide Prescription & OTC Sales by Technology (2002-2016)


2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Technology Biotechnology 10% 11% 12% 13% 14% 15% 16% 17% 18% 19% 20% 21% 21% 21% 21% Conventional/ Unclassified 90% 89% 88% 87% 86% 85% 84% 83% 82% 81% 80% 79% 79% 79% 79% Total Rx & OTC Sales 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% WW Sales ($bn) 2004
56 331 91 478

2002 2003 Technology Biotechnology 38 46 Conventional 261 301 Other Unclassified Sales 75 82 Total Rx & OTC Sales 374 429 Source: EvaluatePharma (25 MAY 2011)

2005
66 347 105 518

2006
79 371 115 565

2007
96 396 128 620

2008
110 418 142 670

2009
119 429 140 688

2010
130 431 146 707

2011
140 444 162 745

2012
151 437 178 765

2013
163 440 191 794

2014
175 450 205 829

2015
184 454 221 860

2016 2016
192 465 237 894

WW Prescription Drug Sales from Biotechnology in 2016: Top 10 Companies


Company Roche Novo Nordisk Sanofi Amgen Pfizer GlaxoSmithKline Abbott Laboratories Merck & Co Eli Lilly Johnson & Johnson WW Sales ($bn) WW Market Share 2010 2016 % CAGR 10-16 2010 2016
23.7 9.9 9.8 13.9 9.3 5.5 6.7 7.0 4.7 5.6 30.6 17.6 15.5 14.6 12.3 9.3 9.2 9.1 6.1 5.7 +4% +10% +8% +1% +5% +9% +6% +4% +5% +0% 18.3% 15.9% 7.7% 7.6% 10.7% 7.2% 4.3% 5.2% 5.4% 3.6% 4.3% 9.2% 8.1% 7.6% 6.4% 4.8% 4.8% 4.8% 3.2% 3.0%

Chg. (+/-)
-2.3% +1.5% +0.5% -3.1% -0.7% +0.6% -0.3% -0.7% -0.4% -1.4%

Rank Chg.
+1 +1 -2 +3 -2 +1 -2

1 2 3 4 5 6 7 8 9 10

Note: Company drug sales from undisclosed products are presumed to be from conventional (small molecule) technology.

Note: Sanofi results for 2010 are not pro-forma for the acquisition of Genzyme. Copyright 2011 EvaluatePharma Ltd. All rights reserved. 8

Top 20 Most Valuable R&D Projects (Ranked by Net Present Value)


Value of Industry Pipeline Declines only 8% Despite Approvals; Degludec Most Valuable Product EvaluatePharma NPV Analyzer finds that the value of the Industry's pipeline declined 8% to $250bn, vs. $272bn as calculated in April 2010. The decrease is a negative indicator for the Industry but masks the positive fact that since April 2010, 8 of last year's top 20 R&D products (by NPV value) have been approved, thus partly crystallizing shareholder value as the risk of failure is reduced and cash flows start to be realised. Approvals include the 4 most valuable products: Prolia/Xgeva (Amgen), Provenge (Dendreon), Benlysta (HGS/GSK) and Incivek (Vertex), which currently have a combined NPV of $30.2bn. Novo Nordisk's Degludec is the most valuable R&D product in the industry based on NPV, with a value of $5.8bn. Top 20 Most Valuable R&D Projects (Ranked by Net Present Value)
WW Product Sales ($m) Rank Product 1 Degludec 2 Tofacitinib (CP-690550) 3 BG-12 4 Incivek 5 Relovair 6 DR Cysteamine 7 AMR101 8 Eliquis 9 Eliquis 10 Bexsero 11 12 13 14 15 16 17 18 19 Company Novo Nordisk Pfizer Biogen Idec Johnson & Johnson Theravance Undisclosed Partner Undisclosed Partner Bristol-Myers Squibb Pfizer Novartis Gilead Sciences Undisclosed Partner Incyte Novo Nordisk Regeneron Johnson & Johnson Anthera Vertex Pfizer Roche Phase (Current) Phase III Phase III Phase III Filed Phase III Phase III Phase III Filed Filed Filed Phase III Phase III Phase III Phase III Filed Filed Phase III Phase III Phase III Phase III Pharmacological Class Insulin JAK-3 inhibitor Fumarate Hep C protease inhibitor Beta 2 adrenoreceptor agonist & corticosteroid Lysosomal transport modulator Omega-3 fatty acid Factor Xa inhibitor Factor Xa inhibitor Meningococcal B vaccine NRTI, HIV integrase inhibitor & CYP3A inhibitor Oncolytic virus JAK-1/2 inhibitor Insulin VEGFr kinase inhibitor Factor Xa inhibitor sPLA2 inhibitor CFTR potentiator c-Met & ALK inhibitor Anti-HER2 MAb-DM1 conjugate 2016 1,389 1,651 1,224 2,243 3,231 2,289 2,150 1,085 879 1,358 758 629 663 1,215 724 541 554 423 23,005 59,093 82,098 new entry new entry new entry new entry new entry new entry new entry new entry new entry new entry new entry new entry new entry Today's NPV ($m) 5,807 4,953 4,666 4,332 4,241 4,155 4,052 3,836 3,592 3,250 3,210 2,618 2,468 2,334 2,310 2,257 2,196 2,142 2,123 1,974 66,517 182,948 249,466 -8% 271,836

Elvitegravir + GS 9350 + Truvada Reolysin Ruxolitinib (INC424) DegludecPlus VEGF Trap-Eye Xarelto Varespladib (A-002) Ivacaftor (VX-770) Crizotinib (PF-02341066)

20 Trastuzumab-DM1

Top 20 Other Total

Source: EvaluatePharma (25 MAY 2011)

NPV of R&D Pipeline APR 2010:

Most Valuable R&D Projects (Ranked by NPV) in April 2010 Which Have Since Been Approved or Suffered Setbacks
Change vs. APR 10 Approved Product Status Change April 2010 NPV ($m) 17,892 5,990 5,884 5,558 3,071 2,623 2,590 2,458 Sub-Total Setback 46,066 5,135 4,342 2,988 2,298 Sub-Total 14,763 60,829 Today's 12,265 5,873 4,645 7,434 3,692 2,947 3,942 930 41,728 504 1,150 1,654 43,382 Change vs. -31% -2% -21% 34% 20% 12% 52% -62% -9% -100% -88% -62% -100% -89% -29%

Prolia/Xgeva Provenge Benlysta Incivek Benlysta Brilinta* Esbriet* Viibryd Numax Vorapaxar (SCH 530348) Bydureon Taspoglutide (RG1583) Total

Company Amgen Dendreon HGS Vertex GlaxoSmithKline AstraZeneca InterMune Forest AstraZeneca Merck & Co Amylin Roche

Status (April 2010) Filed Filed Phase III Phase III Phase III Filed Filed Filed Filed Phase III Filed Phase III

Since April10 Approved Approved Approved Approved Approved Approved Approved Approved Setback Setback Setback Setback

NPV ($m) Apr-10 (%)

Source: EvaluatePharma (25 MAY 2011) Note: Theravance to receive royalty payments from GSK on Relovair. DR Cysteamine, AMR101 and Reolysin NPVs based on assumption of future out-licensing, currently being developed by Raptor Pharmaceutical, Amarin and Oncolytics Biotech, respectively. Analysts assume Pfizer to receive co-promotion revenues on Eliquis (apixaban) from BMS. *Brilinta and Esbriet have been approved in the EU but suffered setbacks in the US.

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

Worldwide R&D Spend by Pharma & Biotech Companies (2002-2016)


Global Pharmaceutical R&D Spend Set to Grow by 2.5% (CAGR) to $147bn by 2016; Industry Reinvestment Rate Declining EvaluatePharma estimates that worldwide pharmaceutical R&D totalled $127bn in 2010, a 1.5% increase on 2009. Despite this representing a return to nominal growth compared to the unprecedented 3.0% decline in 2009, the rate of growth has not returned to the double-digit increases seen in R&D spend between 2002 and 2008 and R&D budgets are now forecast to grow at 2.5% per year, to reach $147bn by 2016. Industry reinvestment, measured by R&D spend as a percentage of prescription sales is set to decline from 18.8% in 2010 to 17.3% in 2016. The decline can be attributed to the fact that R&D spend is growing by less than prescription drug sales as global majors streamline and downsize R&D operations after major patent expiries and historically poor R&D investment returns. The other factor is the change in product mix of the prescription drug industry towards generics, which requires a fraction of the R&D spend. Worldwide Total Pharmaceutical R&D Spend in 2002-16 Source: EvaluatePharma (25 MAY 2011)
WW Pharma R&D Spend ($bn) 160 140 120 100 80

+13.7% +11.4% +9.4% 119 107 96 88 79 69


+8.9% CAGR 2002-09

16%
+2.5% CAGR 2010-16

+12.1% +10.4% 129 +8.9% 125 127 133 134 137 141

144

147

14% 12% 10% 8%

+4.5% +1.5% +1.0%

6%

60 40

+2.2% +2.7% +2.2% +2.4% 4%


2% 0%

20 0 2002 2003 2004 2005 2006 2007 2008

-3.0%

-2% -4% 2010 2011 2012 2013 2014 2015 2016

Worldwide R&D Spend by Pharma & Biotech Companies (2002-2016)


WW Prescription Sales ($bn) Year 2002 2003 2004 2005 Pharma R&D Spend Growth per Year WW Prescription Sales R&D as a % of WW Rx Sales
69.2 354 19.6% 78.7 406 19.4% 87.7 454 19.3% 95.9 493 19.5%

2006
107.5 539 19.9%

2007
118.7 592 20.0%

2009

2008
129.2 640 20.2%

2009
125.3 -3.0% 656 19.1%

2010
127.1 +1.5% 675 18.8%

2011
132.9 +4.5% 711 18.7%

2012
134.1 +1.0% 730 18.4%

2013
137.1 +2.2% 757 18.1%

2014
140.8 +2.7% 791 17.8%

2015
143.9 +2.2% 820 17.6%

+13.7% +11.4% +9.4% +12.1% +10.4% +8.9%

+2.4% 853 17.3%

CAGR 10-16 on Pharma R&D Spend +2.5% Cumulative R&D Spend (2002-10) $939 bn Note: Industry sales based on Top 500 pharmaceutical and biotech companies. Forecast pharmaceutical research and development spend based on a consensus of leading equity analysts' estimates for company level R&D spend, extrapolated to pharmaceutical R&D when a company has non-pharmaceutical R&D activity.

Source: EvaluatePharma (25 MAY 2011)

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

R&D Spend Growth %


2016
147.4

10

Pharmaceutical R&D Spend in 2016: Top 20 Companies


Novartis Tops Pharmaceutical R&D Spend in 2016 EvaluatePharma's consensus forecast finds Novartis spending the most on pharmaceutical research and development by 2016, with a spend of $9.9bn. In 2010 Pfizer had the largest pharmaceutical R&D budget but falls to the 6th biggest spender by 2016. It is the only global major forecast to cut R&D spend between 2010 and 2016. Since April 2010 consensus analyst forecasts for Pfizer's R&D spend have been revised down by $1.2bn in 2016. Pharmaceutical R&D in 2016: Top 10 Companies Source: EvaluatePharma (25 MAY 2011)
9.9 8 6 4 2 0 Pfizer GlaxoSmithKline AstraZeneca Merck & Co Johnson & Johnson Novartis Takeda
Chg. (+/-)
+0.9% -0.0% -2.7% +1.0% -1.3% -2.7% +1.9% +6.7% +3.3% -1.6% +2.8% -1.6% +0.2% +1.8% +0.0% -0.3% -0.9% -5.7% +10.8% -0.1% -0.5% +4% R&D Spend ($bn) CAGR 2010-16 (%)

R&D Spend ($bn)

10

8.5
+1%

8.4
+1%

7.6
+5%

7.4
+4%

7.2
-4%

5.2
+2%

5.0
+1%

4.4
+1%

3.8
+2%

Roche

Pharmaceutical R&D Spend (2010/16): Top 20 Companies & Total Market


Pharma R&D ($bn) 2016 2010
7.9 8.1 7.8 5.7 5.8 9.1 4.5 4.7 4.2 3.4 2.3 3.3 3.1 2.8 1.7 2.3 2.3 2.5 1.8 1.6 85.0 42.2 127.1 9.9 8.5 8.4 7.6 7.4 7.2 5.2 5.0 4.4 3.8 3.6 3.4 3.4 3.2 2.9 2.7 2.6 2.3 1.9 1.9 95.2 52.2 147.4

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Company Novartis Merck & Co Roche GlaxoSmithKline Sanofi Pfizer Johnson & Johnson Eli Lilly AstraZeneca Takeda Bayer Bristol-Myers Squibb Boehringer Ingelheim Amgen Novo Nordisk Abbott Laboratories Daiichi Sankyo Astellas Pharma Otsuka Holdings Merck KGaA Total Top 20 Other Total

CAGR 10-16
+4% +1% +1% +5% +4% -4% +2% +1% +1% +2% +8% +1% +2% +2% +9% +3% +2% -2% +1% +3% +1.9% +3.6% +2.5%

2016 Change vs Apr-10


-0.1 -0.3 -1.0 +0.2 +1.4 -1.2 -0.9 -0.5 -0.1 +0.1 +1.0 +0.1 +0.1 -0.0 +0.4 -0.1 +0.3 +0.3 +0.9 -0.1 +0.6 +1.3 +1.9

R&D As a % of Rx Sales 2010 2016


19.0% 20.1% 22.0% 16.0% 15.9% 16.8% 21.7% 22.8% 13.2% 26.9% 16.3% 21.3% 24.3% 19.3% 15.8% 11.4% 21.1% 24.7% 25.2% 22.0% 18.4% 19.9% 20.1% 19.3% 17.0% 14.7% 14.0% 23.6% 29.6% 16.4% 25.3% 19.1% 19.7% 24.5% 21.1% 15.8% 11.1% 20.3% 19.0% 36.0% 21.9% 18.0%

Source: EvaluatePharma (25 MAY 2011) Note: Forecast pharmaceutical R&D spend based on a consensus of leading equity analysts' estimates for company level R&D spend.

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

Eli Lilly

Sanofi

11

FDA New Drug Approval Analysis (NMEs & Biologicals): 1997 to 2010
Best Year for Approvals since 2004 as Sales Potential Doubles; Number of New Drugs Approved Down 24% EvaluatePharma found that the FDA approved 26 new drugs in 2010, a decrease of 24% from the 2009 figure of 34. The 2010 approvals included 15 new molecular entities (down 4) and 11 biologicals (down 4 on 2009). Despite this decrease in new drug approvals, the quality of the approvals improved significantly over 2009 thanks to the approval of several potential blockbusters: Prevnar 13 (Pfizer), Prolia/Xgeva (Amgen), Provenge (Dendreon), Victoza (Novo Nordisk) and Gilenya (Novartis). Indeed, the quality of the NMEs in 2010 is the highest since 2004, with anticipated USA sales 5 years post launch of $13.3bn, a 119% increase over 2009.
FDA Approval Count vs. Total USA Product Sales 5 Years After Launch Source: EvaluatePharma (25 MAY 2011)
USA Sales 5 Yrs after Launch ($bn) 25
1998 Remicade (JNJ) Singulair (MRK) Celebrex (PFE) Enbrel (AMGN/ WYE) Viagra (PFE) Celexa (FRX) 2002 Neulasta (AGMN) Abilify (BMY/ Otsuka) Zetia (SGP/ MRK) Humira (ABT) Eloxatin (SNY) Product name (company ticker) of products in good years (>$1bn) sales) 2010 Prevnar 13 (PFE) Prolia/Xgeva (AMGN) Provenge (DNDN) Victoza (Novo N) Gilenya (NVS)

20

49 39 40

2004 Avastin (Roche) Cymbalta (LLY) Lyrica (PFE) Spiriva (BI/ PFE)

50

15

33
$14bn 10

35 32
$13bn

38 34
$14bn

40

26
Average 5th Year USA Sales Potential: $8.8bn

28
$8bn $7bn

29 26
$8bn $5bn

31

$13bn

30

26
20 $6bn $5bn

$8bn $7bn 5 $7bn $7bn

10

0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

USA Sales 5yrs Post Launch $bn

No. of NMEs Approved

FDA Approval Count (NMEs & Biologicals) vs. 5th Year after Launch USA Product Sales
Year No. of NMEs Approved No. of Biologicals Approved Total NMEs + Biologicals % Chg. USA Sales 5yrs Post Launch $bn % Chg. 1997
39 10 49 7.4

1998
30 9 39 -20% 13.5 +82%

1999
35 5 40 +3% 7.1 -48%

2000
27 6 33 -18% 7.4 +4%

2001
24 8 32 -3% 8.5 +14%

2002
17 9 26 -19% 12.7 +50%

2003
21 14 35 +35% 8.3 -34%

2004
31 7 38 +9% 14.1 +69%

2005
18 10 28 -26% 6.5 -54%

2006
18 11 29 +4% 8.1 +25%

2007
16 10 26 -10% 5.1 -37%

2008
21 10 31 +19% 5.0 -2%

2009
19 15 34 +10% 6.1

2010
15 11 26 -24% 13.3

+20% +119%

Top 10 New Molecular Entities in 2010: Ranked on USA Consensus Sales in 2015
US Sales 2010 2015
1,761 34 48 207 15 109 56 26 170 2,329 1,864 1,818 1,165 1,077 883 657 631 560 423 1,898

Product Company Pfizer 1 Prevnar 13 Amgen 2 Prolia/Xgeva Dendreon 3 Provenge Novo Nordisk 4 Victoza Novartis 5 Gilenya Boehringer Ingelheim 6 Pradaxa Sanofi 7 Jevtana Dainippon Sumitomo Pharma 8 Latuda Roche 9 Actemra Eisai 10 Halaven Other Total Source: EvaluatePharma (25 MAY 2011)

Approved
Feb 2010 Jun 2010 Apr 2010 Jan 2010 Sep 2010 Oct 2010 Jun 2010 Oct 2010 Jan 2010 Nov 2010

Note: Sales forecasts based on a consensus of leading equity analysts' estimates. 5th year USA sales for products approved before 2005 are based on actual company reported sales. E.g. Erbitux (BMS), approved in FEB 2004 has company reported US sales in 2009 (5th year post US launch) of $671m.

2,425 13,306

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

No. of New Drugs

60

12

Worldwide Rx & OTC Sales by Therapy Area in 2016


Oncology Remains Largest Segment; Anti-coagulants Set to Record Highest Growth to 2016 Oncology remains the largest segment to 2016, with strong growth from in-line products and new products, off-setting a number of major patent expiries over the period. Over the period 2010 to 2016, EvaluatePharma finds that sales from anti-coagulants are set to grow at an annual rate of 13.5%. This strong growth is being driven by new oral treatments for the prevention of stroke, MI and thrombosis.

Analysis on Source: EvaluatePharma (25in 2012, Market Share & Sales Growth (2007-12) Top 10 Therapy Sales MAY 2011)
WW Market Share % 14% 12% 10% 8% 6% 4% 2%
Key Patent Expiry Lipitor (PFE) in 2011 Key Patent Expiries Angiotensin II antagonists segment Diovan (NVS) in 2012, Avapro (BMY/ SAN) in 2012, Micardis (BI) in 2014. Key Drivers Avastin (Roche), Rituxan (Roche) Tasigna (NVS), Afinitor (NVS) Provenge (DNDN), Revlimid (CELG) Key Patent Expiries Taxotere (SAN), Arimidex (AZN) Gleevec (NVS), Gemzar (LLY) Femara (NVS)

Analysis on Top 10 Therapy Areas in 2016, Market Share & Sales Growth (2010-16)

Oncology*

Anti-rheumatics Bronchodilators Anti-hypertensives Vaccines

Anti-diabetics
Key Drivers: New oral treatments Xarelto (BAY/ J&J) Eliquis (BMS / PFE) Pradaxa (BI)

Anti-virals Anti-hyperlipidaemics Dermatologicals

Anti-coagulants

0% -10.0%

-5.0%

+0.0%

+5.0%

+10.0%

+15.0%

+20.0%

% Sales Growth: CAGR 2010-16

Note: Bubble = WW Sales in 2016 WW Rx & OTC Sales by EvaluatePharma Therapy Area (2010/16): Top 15 Categories & Total Market WW Sales ($bn) Therapy Area
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Oncology* Anti-diabetics Anti-rheumatics Vaccines Anti-virals Anti-hypertensives Bronchodilators Anti-hyperlipidaemics Dermatologicals Anti-coagulants Sensory organs MS therapies Anti-bacterials Anti-fibrinolytics Bone calcium regulators Top 15 Other Total WW Rx & OTC Sales 2010
60.0 30.6 32.7 25.3 22.1 40.9 32.8 29.8 12.4 7.4 13.8 11.1 15.4 9.1 9.9 353 354 707

CAGR
% Growth
+7.1% +7.5% +4.6% +6.3% +6.6% -4.0% -1.1% -2.8% +4.6% +13.5% +2.0% +4.5% -1.4% +4.9% +2.2% +3% +4% +4%

2016
90.5 47.3 42.8 36.5 32.5 32.1 30.7 25.2 16.2 15.8 15.5 14.5 14.1 12.1 11.3 437 457 894

2016 Change vs. Apr-2010


+17.7 +2.8 +0.0 -0.5 +0.2 +4.6 +5.6 +4.9 +4.4 +1.7 -0.9 +2.3 +1.9 -0.3 -2.7 +41.6

WW Market Share 2010 2016


8.5% 4.3% 4.6% 3.6% 3.1% 5.8% 4.6% 4.2% 1.7% 1.0% 2.0% 1.6% 2.2% 1.3% 1.4% 50.0% 50.0% 100.0% 10.1% 5.3% 4.8% 4.1% 3.6% 3.6% 3.4% 2.8% 1.8% 1.8% 1.7% 1.6% 1.6% 1.4% 1.3% 48.9% 51.1% 100.0%

Chg. (+/-)
+1.6% +1.0% +0.2% +0.5% +0.5% -2.2% -1.2% -1.4% +0.1% +0.7% -0.2% +0.0% -0.6% +0.1% -0.1% -1.1% +1.1%

Rank Chg. (+/-)


+3 +1 +3 +3 -4 -4 -2 +2 +5 -1 -4 -2

Total 'Rx & OTC Sales' includes:


WW Unbranded Generic Sales OTC Pharmaceuticals Source: EvaluatePharma (25 MAY 2011)
61.2 31.9 96.2 41.4 +8% +4% 8.7% 4.5% 10.8% 4.6% +2.1% +0.1%

Note: Industry sales based on Top 500 pharmaceutical and biotech companies. Sales in 2010 based on company reported data. Sales forecasts to 2016 based on a consensus of leading equity analysts' estimates for product sales and segmental sales. *Compared to April 2010, EvaluatePharma now classifies Revlimid (Celgene, 2016 Sales: $5,550m) and Afinitor (Novartis, 2016 Sales: 2,058) as oncology products (previously classified as immunostimulants).

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

13

Oncology Market to 2016


Roche Set to Continue Domination of Oncology Market EvaluatePharma found that Roche commanded an impressive 33.8% market share of the worldwide oncology market in 2010. Roche's dominance is set to continue with consensus forecasts predicting a 28.5% share of the $90.5bn oncology market in 2016. Dendreon is set to enter the top 10 by 2016 owing to the 2010 launch of its cancer vaccine (Provenge), which is forecast to achieve sales of $2.6bn in 2016. Bristol-Myers Squibb's oncology sales are forecast to grow by 18% between 2010 and 2016, moving the company to 4th spot in the company rankings, due to strong performances from Sprycel (dasatinib), Yervoy (ipilimumab) and Ixempra (ixabepilone). Patent expiries on Arimidex and Casodex are set to hit AstraZeneca which drops 5 ranking positions to 8th spot in 2016.

Analysis on Worldwide Sales, Market Share & Sales Growth (2010-16)


Source: EvaluatePharma (25 MAY 2011)
WW Market Share % 40% 35% 30% 25% 20% 15% 10% Novartis* 5% 0% -5% Pfizer Celgene* Bristol-Myers Squibb
NVS: Tasigna set to replace lost Gleevec sales by 2016 (Gleevec patent expiry JUL 2015). Femara patent expiry JUN 2011. Roche: Set to control world's top 3 leading oncology products by 2016 with Avastin, Rituxan and Herceptin. Few patent concerns.

Roche

BMS: Strong growth from Sprycel, Yervoy and Ixempra.

+0%

+5%

+10%

+15%

+20%

+25%

% Sales Growth: CAGR 2010-16

Note: Bubble = WW Sales in 2016

Top 10 Companies & Total Worldwide Oncology Sales 2010-16


WW Sales ($m) Rank Company 1 Roche 2 Novartis* 3 Celgene* 4 Bristol-Myers Squibb 5 Pfizer 6 Eli Lilly 7 Sanofi 8 AstraZeneca 9 GlaxoSmithKline 10 Dendreon Top 10 Other Total Industry 2010 20,256 6,321 3,480 1,800 2,682 3,338 3,740 4,045 1,064 48 46,775 13,188 59,963 2016 25,803 7,463 7,354 4,899 4,225 4,046 3,696 3,171 2,993 2,617 66,269 24,217 90,486 +17660 2016 Change vs. Apr-2010 +1466 +2218 +6455 +1038 +21 -362 +1224 +138 +432 +954 +13584 CAGR 2010-16 +4% +3% +13% +18% +8% +3% -0% -4% +19% +95% +5% +9% +6% WW Market Share 2010 33.8% 10.5% 5.8% 3.0% 4.5% 5.6% 6.2% 6.7% 1.8% 0.1% 78.0% 22.0% 100.0% 2016 28.5% 8.2% 8.1% 5.4% 4.7% 4.5% 4.1% 3.5% 3.3% 2.9% 73.2% 26.8% 100.0% Rank Chg. 2010-16 +2 +4 +2 -3 -5 +5 +31

Source: EvaluatePharma (25 MAY 2011); Consensus sales from equity analysts' reports

Top 5 Oncology Products Worldwide in 2016


WW Sales ($m) Rank Product 1 Avastin 2 Rituxan 3 Herceptin 4 Revlimid 5 Alimta Generic Name bevacizumab rituximab trastuzumab lenalidomide pemetrexed disodium Company Roche Roche + Biogen Idec Roche Celgene Eli Lilly Pharma Class Anti-VEGF MAb Anti-CD20 MAb Anti-HER2 (ErbB-2) MAb Immunomodulator Thymidylate synthase inhibitor 2010 6,214 6,113 5,221 2,469 2,209 2016 7,831 7,684 6,466 5,550 2,891 CAGR 2010-16 +3% +3% +3% +12% +4% WW Market Share 2010 10.4% 10.2% 8.7% 4.1% 3.7% 2016 8.7% 8.5% 7.1% 6.1% 3.2% Current Status Marketed Marketed Marketed Marketed Marketed

Note: Oncology Includes: Alkaloids, Alkylating agents, Anti-metabolites, Anti-neoplastic MAbs, Cancer vaccines, Cytotoxic antibiotics, Hormone therapies, Platinum compounds and other anti-cancer. Excludes anti-emetics and anti-anaemics used in chemotherapy-induced anaemia. Also excludes: Interferons, immunostimulants & immunosuppressants. *Compared to April 2010, EvaluatePharma now classifies Revlimid (Celgene, 2016 Sales: $5,550m) and Afinitor (Novartis, 2016 Sales: $2,058m) as oncology products (previously classified as immunostimulants).

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

14

Anti-Diabetic Market to 2016


Novo Nordisk to Extend Dominance in Anti-Diabetic Market EvaluatePharma finds Novo Nordisk will continue as the market leader in anti-diabetic products, increasing market share from 26.6% to 30.8% between 2010 and 2016 due to strong growth from its insulin franchise (including the potential new longer-acting insulin product, Degludec) and Victoza (GLP-1). Indeed, positive news flow on Victoza and Degludec helped increase 2016 forecasts for the company's anti-diabetic sales by $3.0bn compared to April 2010. Bristol-Myers Squibb and AstraZeneca are set to become significant players in the diabetes market with strong growth forecast from their new DPP-IV inhibitor, Onglyza, over the period.

Analysis on Worldwide Sales, Market Share & Sales Growth (2010-16)


Source: EvaluatePharma (25 MAY 2011) WW Market Share % 40% 35% 30% 25% 20% 15% 10% Takeda 5% 0% -10% Eli Lilly
MRK: Strong growth in DPP-IV inhibitor franchise Januvia/Janumet. Takeda: Actos generic competition expected 2012. New DPP-IV inhibitor Nesina set to cushion the blow. Novo: Solid growth in its core insulin franchise (including Degludec) and GLP-1 Victoza.

Novo Nordisk

Sanofi Merck & Co

-5%

+0%

+5%

+10%

+15%

+20%

Note: Bubble = WW Sales in 2016

% Sales Growth: CAGR 2010-16

Top 10 Companies & Total Worldwide Anti-Diabetic Sales 2010-16


WW Sales ($m) Rank Company 1 Novo Nordisk 2 Sanofi 3 Merck & Co 4 Takeda 5 Eli Lilly 6 Bristol-Myers Squibb 7 Amylin Pharmaceuticals 8 Novartis 9 Servier 10 Bayer Top 10 Other Total Industry 2010 8,144 5,704 3,369 4,975 3,294 264 651 500 610 463 27,975 2,644 30,619 2016 14,575 7,595 6,691 3,801 3,774 2,470 1,139 1,079 645 522 42,291 4,989 47,280 +2797 2016 Change vs. Apr-2010 +3008 +1030 +630 +355 -427 +326 -1376 +419 +16 +91 +4072 CAGR 2010-16 +10% +5% +12% -4% +2% +45% +10% +14% +1% +2% +6% +9% +6% WW Market Share 2010 26.6% 18.6% 11.0% 16.2% 10.8% 0.9% 2.1% 1.6% 2.0% 1.5% 91.4% 8.6% 100.0% 2016 30.8% 16.1% 14.2% 8.0% 8.0% 5.2% 2.4% 2.3% 1.4% 1.1% 89.4% 10.6% 100.0% Rank Chg. 2010-16 +1 -1 +7 +1 -2 -1

Source: EvaluatePharma (25 MAY 2011); Consensus sales from equity analysts' reports

Top 5 Anti-Diabetic Products Worldwide in 2016


WW Sales ($m) Rank Product 1 Januvia/Janumet 2 Lantus 3 NovoRapid 4 Human insulin & devices 5 Humalog Generic Name sitagliptin insulin glargine insulin aspart Company Merck + Ono + Almirall Sanofi Novo Nordisk Pharma Class DPP-IV inhibitor Insulin Insulin Insulin Insulin 2010 3,503 4,658 2,120 2,502 2,054 2016 6,800 5,585 3,672 2,507 2,223 CAGR 2010-16 +12% +3% +10% +0% +1% WW Market Share 2010 11.4% 15.2% 6.9% 8.2% 6.7% 2016 14.4% 11.8% 7.8% 5.3% 4.7% Current Status Marketed Marketed Marketed Marketed Marketed

insulin recombinant Novo Nordisk human insulin lispro Eli Lilly

Note: Bristol-Myers Squibb to book worldwide end-user sales on Onglyza, co-promoted worldwide (ex Japan) with AstraZeneca.

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

15

Anti-Rheumatics Market to 2016


Abbott Laboratories Set to be Clear No. 1 in 2016 EvaluatePharma's consensus forecast predicts Abbott Laboratories will remain the world's number 1 player in anti-rheumatic sales in 2016. Abbott Laboratories' strong performance is driven by strong growth from Humira (adalimumab), which is set to achieve global sales of $9.7bn in 2016. This makes the product the leading Anti-TNF product in 2016, ahead of Merck/J&J's Remicade/Simponi franchise which is forecast to reach $8.0bn by 2016 and Pfizer/Amgen's Enbrel which is forecast to sell $7.2bn in 2016. Strong forecast growth from Cimzia and Actemra is set to propel UCB and Roche, respectively, to positions 8 and 9 in the company rankings.

Analysis on Worldwide Sales, Market Share & Sales Growth (2010-16)


Source: EvaluatePharma (25 MAY 2011)
WW Market Share % 30%
ABT: Continued growth for Humira (adalimumab) in the TNF inhibitor market to 2016.

25%

Abbott Laboratories 20%


AMGN: Enbrel sales forecast to decline owing to increased competition in both RA and psoriasis.

Pfizer*

15%

10% Johnson & Johnson Amgen 5%

Merck & Co

0% -6% -4% -2% +0% +2% +4% +6% +8%

Note: Bubble = WW Sales in 2016

% Sales Growth: CAGR 2010-16

Top 10 Companies & Total Worldwide Anti-rheumatic Sales 2010-16


WW Sales ($m) Rank Company 1 Abbott Laboratories 2 Pfizer* 3 Merck & Co 4 Johnson & Johnson 5 Amgen 6 Bristol-Myers Squibb 7 Bayer 8 UCB 9 Roche 10 Mitsubishi Tanabe Top 10 Other Total Industry 2010 6,548 6,496 3,209 3,491 3,534 733 917 263 221 707 26,119 6,541 32,660 2016 8,959 7,125 4,096 3,591 2,977 1,709 1,381 1,354 1,181 1,111 33,484 9,324 42,807 +4 2016 Change vs. Apr-2010 -679 +1885 +70 -854 -311 -89 +343 -105 -618 +171 -186 CAGR 2010-16 +5% +2% +4% +0% -3% +15% +7% +31% +32% +8% +4% +5% +4% WW Market Share 2010 20.0% 19.9% 9.8% 10.7% 10.8% 2.2% 2.8% 0.8% 0.7% 2.2% 80.0% 20.0% 100.0% 2016 20.9% 16.6% 9.6% 8.4% 7.0% 4.0% 3.2% 3.2% 2.8% 2.6% 78.2% 21.8% 100.0% Rank Chg. 2010-16 +2 -2 +3 +1 +7 +8 +2

Source: EvaluatePharma (25 MAY 2011); Consensus sales from equity analysts' reports

Top 5 Anti-rheumatic Products Worldwide in 2016


WW Sales ($m) Rank Product 1 Humira 2 Enbrel 3 Remicade** 4 Simponi** 5 CP-690550 Generic Name adalimumab etanercept infliximab golimumab tofacitinib citrate Company Abbott + Eisai Amgen + Pfizer + Takeda Pharma Class Anti-TNFa MAb TNFa inhibitor 2010 6,742 7,257 6,520 324 2016 9,696 7,190 6,107 1,942 1,651 CAGR 2010-16 +5% -0% -1% +29% n/m WW Market Share 2010 20.6% 22.2% 20.0% 1.0% 2016 22.6% 16.8% 14.3% 4.5% 3.9% Current Status Marketed Marketed Marketed Marketed Phase III

J&J + Merck + Anti-TNFa MAb Mitsubishi Tanabe Merck + J&J Pfizer Anti-TNFa MAb Janus kinase-3 (JAK-3) inhibitor

Note: Anti-rheumatic sales include TNF inhibitors, COX-2 inhibitors, NSAIDs and new treatments in development. TNF inhibitor sales include RA, Crohn's and Psoriasis. Pfizer books US co-promotion revenues on Enbrel. *Compared to April 2010, EvaluatePharma now classifies CP-690550 (Pfizer, 2016 Sales: $1,651m) as an Other Anti-rheumatic (previously classified as an immunosuppressant). **Combined Remicade and Simponi sales $8.0bn. Simponi (golimumab) is Merck and J&J's next generation product to Remicade (infliximab). Copyright 2011 EvaluatePharma Ltd. All rights reserved. 16

Vaccine Market to 2016


GlaxoSmithKline Retains Number 1 Spot in 2016 EvaluatePharma finds that GSK retains the number 1 spot in vaccines in 2016, despite seeing its market share drop from 26.4% in 2010 to 22.0% in 2016. Pfizer is set to have the fastest growing vaccines division within global majors between 2010 and 2016, with predicted average annual growth of 9%, driven by its pneumococcal vaccines, including the switch from Prevnar to Prevnar 13, the company's new vaccine which protects against an additional 6 strains of pneumococcal bacteria. .

Analysis on Worldwide Sales, Market Share & Sales Growth (2010-16)


Source: EvaluatePharma (25 MAY 2011)
WW Market Share % 30%
Pfizer Strong growth from newly acquired pneumococcal vaccines (Prevnar & Prevnar 13).

25% GlaxoSmithKline 20% Sanofi + 50% Sanofi Pasteur MSD

Pfizer

15% Merck & Co + 50% Sanofi Pasteur MSD

10%

Novartis

5%

Novartis Strong contribution expected from new meningococcal vaccines. Bexsero (2016 sales: $1.0bn) and Menveo sales (2016 sales: $643m).

0% +0% +2% +4% +6% +8% +10% +12%

Note: Bubble = WW Sales in 2016

% Sales Growth: CAGR 2010-16

Top 10 Companies & Total Worldwide Vaccine Sales 2010-16


WW Sales ($m) Rank Company 1 GlaxoSmithKline 2 Sanofi + 50% Sanofi Pasteur MSD 2010 6,689 5,662 3,669 4,093 2,101 504 296 231 234 346 23,825 1,521 25,346 2016 8,034 7,984 6,217 5,472 3,395 934 440 407 404 351 33,638 2,861 36,498 -464 2016 Change vs. Apr-2010 -139 +1439 +38 +389 -59 +190 -76 -16 n/m +77 +1844 CAGR 2010-16 +3% +5% +9% +4% +8% +11% +7% +10% +10% +0% +5% +9% +5% WW Market Share 2010 26.4% 19.9% 14.5% 13.7% 8.3% 2.0% 1.2% 0.9% 0.9% 1.4% 89.2% 10.8% 100.0% 2016 22.0% 19.1% 17.0% 12.2% 9.3% 2.6% 1.2% 1.1% 1.1% 1.0% 86.5% 13.5% 100.0% Rank Chg. 2010-16 +1 -1 +1 +3 +1 -3

3 Pfizer Merck & Co + 50% Sanofi 4 Pasteur MSD 5 Novartis 6 CSL 7 Baxter International 8 Abbott Laboratories 9 Takeda 10 Mitsubishi Tanabe Top 10 Other Total Industry

Source: EvaluatePharma (25 MAY 2011); Consensus sales from equity analysts' reports

Top 5 Vaccine Products Worldwide in 2016


WW Sales ($m) Rank Product 1 Prevnar 13 2 PENTAct-HIB 3 Fluzone Hepatitis Vaccine 4 Franchise 5 Pediarix Generic Name pneumococcal vaccine DTPw, Hib & polio vaccine influenza vaccine hepatitis A & B vaccine DTP, hepatitis B & polio vaccine Company Pfizer Sanofi Sanofi + Sanofi Pasteur MSD GlaxoSmithKline GlaxoSmithKline 2010 2,416 1,306 1,341 1,113 1,082 2016 5,805 1,922 1,806 1,318 1,310 CAGR 2010-16 +13% +6% +4% +2% +3% WW Market Share 2010 9.5% 5.2% 5.3% 4.4% 4.3% 2016 15.9% 5.3% 4.9% 3.6% 3.6% Current Status Marketed Marketed Marketed Marketed Marketed

Note: Sanofi Pasteur MSD is a European joint venture between Merck & Co and Sanofi. Copyright 2011 EvaluatePharma Ltd. All rights reserved. 17

Anti-Virals Market to 2016


Gilead Sciences to Dominate Anti-Virals to 2016 EvaluatePharma finds Gilead Sciences commands a 29.9% market share of the anti-virals area by 2016, with sales set to increase 7% annually between 2010 and 2016. Conversely, GSK is set to fall from 2nd to 5th spot over the same period, due to continued sales decline of its once marketleading herpes treatment, Valtrex, and the expected poor performance from its previously market-dominating HIV franchise. Merck, Vertex and Johnson & Johnson are expected to benefit from the introduction of new treatments for hepatitis C over the period.

Analysis on Worldwide Sales, Market Share & Sales Growth (2010-16)


Source: EvaluatePharma (25 MAY 2011) WW Market Share % 40% 35% 30% 25% 20% 15% 10% GlaxoSmithKline 5% 0% -20%
J&J: Growth driven by new hep C protease inhibitor Incivek (telaprevir). GSK: Hit by patent expiries (Valtrex - DEC 2009). Weak performance predicted from HIV franchise. Gilead: Set to continue dominance in innovative HIV combinational therapy.

Gilead Sciences

MRK: Strong growth from HIV integrase inhibitor Isentress (raltegravir) and new hep C protease inhibitor Victrelis (boceprevir).

Johnson & Johnson Bristol-Myers Squibb Merck & Co

-10%

+0%

+10%

+20%

+30%

+40%

Note: Bubble = WW Sales in 2016

% Sales Growth: CAGR 2010-16

Top 10 Companies & Total Worldwide Anti-virals Sales 2010-16


WW Sales ($m) Rank Company 1 Gilead Sciences 2 Johnson & Johnson 3 Merck & Co 4 Bristol-Myers Squibb 5 GlaxoSmithKline 6 Vertex Pharmaceuticals 7 Abbott Laboratories 8 Roche 9 SIGA Technologies 10 AstraZeneca Top 10 Other Total Industry 2010 6,537 1,133 1,517 2,748 4,897 1,619 1,607 646 20,704 1,404 22,107 2016 9,694 4,514 3,430 3,217 2,687 1,730 1,068 938 612 563 28,453 3,999 32,452 +195 2016 Change vs. Apr-2010 -1072 -762 +449 +128 +309 +848 -722 -61 +432 -898 -1350 CAGR 2010-16 +7% +26% +15% +3% -10% n/m -7% -9% n/m -2% +5% +16% +6% WW Market Share 2010 29.6% 5.1% 6.9% 12.4% 22.2% 0.0% 7.3% 7.3% 2.9% 93.7% 6.3% 100.0% 2016 29.9% 13.9% 10.6% 9.9% 8.3% 5.3% 3.3% 2.9% 1.9% 1.7% 87.7% 12.3% 100.0% Rank Chg. 2010-16 +5 +3 -1 -3 New Entry -3 -3 New Entry -2

Source: EvaluatePharma (25 MAY 2011); Consensus sales from equity analysts' reports

Top 5 Anti-viral Products Worldwide in 2016


WW Sales ($m) Rank Product 1 Incivek 2 Atripla 3 Truvada 4 Isentress 5 Reyataz Generic Name telaprevir efavirenz; emtricitabine; tenofovir emtricitabine; tenofovir Company J&J + Vertex + Mitsubishi Gilead Sciences Gilead + Torii Pharma Class Hepatitis C protease inhibitor NNRTI & NRTI NRTI HIV integrase inhibitor Protease inhibitor 2010 2,927 2,746 1,090 1,479 2016 4,226 3,687 3,345 2,222 1,883 CAGR 2010-16 n/m +4% +3% +13% +4% WW Market Share 2010 13.2% 12.4% 4.9% 6.7% 2016 13.0% 11.4% 10.3% 6.8% 5.8% Current Status Approved Marketed Marketed Marketed Marketed

raltegravir potassium Merck & Co atazanavir sulfate Bristol-Myers Squibb

Note: GlaxoSmithKline consolidates 100% of the revenues from ViiV Healthcare, a joint venture with Pfizer for the marketing of the two companies' HIV anti-virals.

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

18

2016: Top 50 Selling Products in the World


2016 Forecasts Upgraded by $33.8bn (+5% Upgrade) Since April 2010; Humira No.1 in 2016 EvaluatePharma finds that total 2016 forecasts for the individual products have increased by $33.8bn (+5.4%)* since April 2010. In the top 10 products the largest upward revisions since April 2010 are Crestor (AstraZeneca) and Seretide/Advair (GSK), which saw their 2016 forecasts increase by $1.2bn and $1.8bn, respectively, due to announcements which indicated a reduced generic threat to 2016. The largest global brand in 2016 is predicted to be Humira, sold by Abbott Laboratories and Eisai (Japan), which is forecast to reach $9.7bn in 2016
WW Product Sales ($m) Product 1 Humira 2 Avastin 3 Rituxan 4 Crestor 5 Enbrel 6 Seretide/Advair 7 Januvia/Janumet 8 Herceptin 9 Remicade 10 Prevnar 13 11 Lantus 12 Revlimid 13 Incivek 14 Lyrica 15 Xarelto 16 Atripla 17 NovoRapid 18 Neulasta 19 Xgeva/Prolia 20 Truvada 21 DR Cysteamine 22 Spiriva 23 Micardis 24 Lucentis 25 Benicar/Olmetec 26 Symbicort 27 Benlysta 28 Alimta 29 Lipitor 30 Privigen 31 Provenge 32 Advate 33 Botox 34 Gilenya 35 Human insulin & devices 36 Zetia 37 Copaxone 38 Plavix 39 Pradaxa 40 Lovenox/Clexane 41 Aranesp 42 Gleevec/Glivec 43 AMR101 44 Cialis/Adcirca Generic Name adalimumab bevacizumab rituximab rosuvastatin calcium etanercept fluticasone propionate; salmeterol xinafoate sitagliptin trastuzumab infliximab pneumococcal vaccine insulin glargine lenalidomide telaprevir pregabalin rivaroxaban efavirenz; emtricitabine; tenofovir insulin aspart pegfilgrastim denosumab emtricitabine; tenofovir cysteamine bitartrate tiotropium telmisartan ranibizumab olmesartan budesonide; formoterol fumarate dihydrate belimumab pemetrexed disodium atorvastatin calcium immune globulin (human) sipuleucel-T factor VIII (procoagulant) botulinum toxin type A fingolimod insulin recombinant human ezetimibe glatiramer acetate clopidogrel bisulfate dabigatran etexilate enoxaparin sodium darbepoetin alfa imatinib mesylate icosapent ethyl tadalafil Company Abbott + Eisai Roche Roche + Biogen Idec AstraZeneca + Shionogi + Chiesi Amgen + Pfizer + Takeda GSK + Almirall + Faes Merck + Ono + Almirall Roche J&J + Merck + Mitsubishi Tanabe Pfizer Sanofi Celgene J&J + Vertex + Mitsubishi Pfizer + Eisai Bayer + J&J Gilead Sciences Novo Nordisk Amgen + Kyowa Hakko Amgen + GSK + Daiichi Sankyo Gilead + Torii Raptor Pharmaceutical Pharmacological Class Anti-TNFa MAb Anti-VEGF MAb Anti-CD20 MAb Statin/ HMG CoA reductase inhibitor TNFa inhibitor Beta 2 adrenoreceptor agonist & corticosteroid DPP-IV inhibitor Anti-HER2 (ErbB-2) MAb Anti-TNFa MAb Pneumococcal vaccine Insulin Immunomodulator Hepatitis C protease inhibitor Alpha 2 delta ligand Factor Xa inhibitor NNRTI & NRTI Insulin Colony stimulating factor Anti-RANKL MAb NRTI Lysosomal transport modulator 2010 6,742 6,214 6,113 6,106 7,257 8,067 3,503 5,221 6,520 2,416 4,658 2,469 0 3,077 100 2,927 2,120 3,558 41 2,746 3,799 3,258 2,935 2,487 2,760 2,209 11,968 1,565 48 1,800 1,435 15 2,502 2,297 3,300 9,148 265 3,724 2,974 4,265 1,784 2016 9,696 7,831 7,684 7,518 7,190 6,953 6,800 6,466 6,107 5,805 5,585 5,550 4,226 3,998 3,991 3,687 3,672 3,442 3,361 3,345 3,231 3,223 3,070 3,062 3,035 2,992 2,892 2,891 2,791 2,620 2,617 2,612 2,596 2,587 2,507 2,502 2,444 2,443 2,384 2,376 2,348 2,293 2,289 2,273 +4% +4% -19% +8% +77% +5% +9% +109% +0% +1% -4% -17% +37% -6% -3% -8% -2% -1% +1% +3% +1% +4% +69% +3% +8% -0% +88% +3% % Growth +5% +3% +3% +3% -0% -2% +10% +3% -1% +13% +3% +12% Market Status Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Approved Marketed Marketed Marketed Marketed Marketed Marketed Marketed Phase III Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Phase III Marketed 2016 Change vs Apr-10 -405 -1078 +897 +1242 -119 +1768 +791 +300 +380 +4081 +292 +702 +554 -78 +366 +165 +415 +344 -1799 -52 +3231 -1366 +708 -367 +260 +638 +151 -384 +118 +745 +955 -362 +244 +1825 +392 +247 -222 +772 +1210 -369 -224 -216 +2289 +254 -4% -12% +13% +20% -2% +34% +13% +5% +7% +237% +6% +14% +15% -2% +10% +5% +13% +11% -35% -2% n/m -30% +30% -11% +9% +27% +6% -12% +4% +40% +57% -12% +10% +239% +19% +11% -8% +46% +103% -13% -9% -9% n/m +13%

Boehringer Ingelheim + Pfizer Muscarinic antagonist Boehringer + Astellas + Bayer Angiotensin II antagonist Novartis + Roche Daiichi Sankyo + Forest AstraZeneca + Sigma-Tau Human Genome Sciences + GSK Eli Lilly Pfizer + Astellas + Almirall CSL Dendreon Baxter International Allergan + GSK Novartis Novo Nordisk Merck & Co Teva + Sanofi Sanofi + BMS Boehringer Ingelheim Sanofi Amgen + Kyowa Hakko Novartis Amarin Anti-VEGF MAb Angiotensin II antagonist Beta 2 adrenoreceptor agonist & corticosteroid Anti-B lymphocyte stimulator (BLyS) MAb Thymidylate synthase inhibitor Statin/ HMG CoA reductase inhibitor Immunoglobulin Prostate cancer vaccine Factor VIII Botulinum toxin S1P receptor modulator Insulin Cholesterol absorption inhibitor MS agent Platelet ADP antagonist Thrombin inhibitor Heparin, low molecular weight (LMWH) Erythropoietin Tyrosine kinase inhibitor Omega-3 fatty acid

Eli Lilly + United Therapeutics Phosphodiesterase V (PDE5) + Nippon Shinyaku inhibitor Novartis Merck KGaA + BMS Eli Lilly Merck & Co Novo Nordisk Takeda + J&J BCR-ABL, PDGFr & c-kit tyrosine kinase inhibitor Anti-EGFr MAb Insulin HIV integrase inhibitor GLP-1 agonist Proteasome inhibitor

45 Tasigna 46 Erbitux 47 Humalog 48 Isentress 49 Victoza 50 Velcade

nilotinib cetuximab insulin lispro raltegravir potassium liraglutide bortezomib

399 1,751 2,054 1,090 413 1,801 151,899 562,232

2,272 2,237 2,223 2,222 2,220 2,208 190,364 656,072

+28% +4% +1% +11% +27% +3% +3% +2%

Marketed Marketed Marketed Marketed Marketed Marketed

+166 -276 -97 +132 +1261 +1173 +21653 +39493

+8% -11% -4% +6% +131% +113% +13% +6%

Total Total WW Individual Products Forecast in EvaluatePharma

Impact of increased company coverage in EvaluatePharma +5667 Impact of consensus forecasts added since April 2010 for companies completing IPOs in 2010 and 2011 +3642 Estimated change in 2016 consensus forecast for all products forecast in EvaluatePharma +30184

Source: EvaluatePharma (25 MAY 2011) Note: Sales represent company reported sales where available, otherwise based on an average of equity analyst estimates. *$33.8bn is the sum of newly IPO'd companies ($3.6bn), plus estimated change in 2016 consensus forecast for all products forecast ($30.2bn). Copyright 2011 EvaluatePharma Ltd. All rights reserved. 19

2016: Top 50 Selling Products in the USA


Rituxan Edges Ahead of Avastin and Humira; AMR101 Highest Ranking R&D Product EvaluatePharma finds that Roche and Biogen Idec's Rituxan is set to become the top selling USA product in 2016, with sales of $3.6bn, narrowly beating Abbott's Humira, Roche's Avastin and Merck & Co's Januvia/Janumet to the No. 1 spot. Amarin's AMR101, a new Omega-3 fatty acid for dyslipidaemia, is the highest ranked R&D product, at number 13 in the list, with USA sales of $2.3bn in 2016. In total, 2016 forecasts for the top 50 products have increased by $7.0bn since April 2010, whilst all product forecasts have declined $5.8bn, signifying a shift in the concentration of value to the Top 50 products.
USA Product Sales ($m) Product 1 Rituxan 2 Humira 3 Avastin 4 Januvia/Janumet 5 Advair 6 Revlimid 7 Lantus 8 Enbrel 9 Remicade 10 Atripla 11 Prevnar 13 12 Neulasta 13 AMR101 14 Herceptin 15 Xgeva/Prolia 16 Provenge 17 Crestor 18 Benlysta 19 Copaxone 20 Incivek 21 Truvada 22 Lyrica 23 Botox 24 Epogen/Procrit 25 NovoRapid 26 Levemir 27 Vyvanse 28 Lucentis 29 Victoza 30 Eliquis 31 Gammagard 32 Varivax 33 Zetia 34 Gilenya 35 Xarelto 36 Brilinta 37 Humalog 38 Isentress 39 Alimta 40 NovoSeven 41 Premarin 42 Orencia 43 Byetta/Bydureon 44 Onglyza 45 Avonex 46 Xifaxan 47 Velcade 48 Tysabri 49 Advate 50 CP-690550 Generic Name rituximab adalimumab bevacizumab sitagliptin phosphate fluticasone propionate; salmeterol xinafoate lenalidomide Company Roche + Biogen Idec Abbott Laboratories Roche Merck & Co GlaxoSmithKline Celgene Pharmacological Class Anti-CD20 MAb Anti-TNFa MAb Anti-VEGF MAb Dipeptidyl peptidase IV (DPPIV) inhibitor & biguanide Beta 2 adrenoreceptor agonist & corticosteroid Immunomodulator Insulin TNFa inhibitor Anti-TNFa MAb NNRTI & NRTI Pneumococcal vaccine Colony stimulating factor Omega-3 fatty acid Anti-HER2 (ErbB-2) MAb Anti-RANKL MAb Prostate cancer vaccine Statin/ HMG CoA reductase inhibitor Anti-B lymphocyte stimulator (BLyS) MAb MS agent Hepatitis C protease inhibitor NRTI Alpha 2 delta ligand Botulinum toxin Erythropoietin Insulin Insulin Psychostimulant Anti-VEGF MAb Glucagon-like peptide 1 (GLP1) agonist Factor Xa inhibitor Immunoglobulin Varicella vaccine Cholesterol absorption inhibitor Sphingosine 1-phosphate (S1P) receptor modulator Factor Xa inhibitor P2Y12 antagonist Insulin HIV integrase inhibitor Thymidylate synthase inhibitor Factor VII Oestrogen agonist B7 integrin antagonist Glucagon-like peptide 1 (GLP1) agonist Dipeptidyl peptidase IV (DPPIV) inhibitor Interferon beta Ansamycin Proteasome inhibitor Anti-VLA-4 MAb Factor VIII Janus kinase-3 (JAK-3) inhibitor 2010 2,910 2,872 3,068 2,139 4,026 1,433 2,832 3,304 3,099 1,909 1,761 2,654 1,530 34 48 2,640 2,287 1,309 1,424 830 3,594 847 516 634 1,402 207 921 929 1,227 15 1,222 554 957 774 949 547 559 119 1,492 250 594 593 682 61,694 245,150 2016 3,570 3,538 3,450 3,417 3,266 2,949 2,801 2,777 2,621 2,562 2,450 2,383 2,289 2,150 2,063 1,993 1,981 1,980 1,743 1,730 1,719 1,589 1,536 1,509 1,469 1,395 1,338 1,314 1,288 1,271 1,238 1,228 1,227 1,220 1,215 1,170 1,155 1,147 1,093 1,067 1,062 1,034 1,033 1,020 1,016 1,001 998 990 989 987 88,028 251,741 +5% +2% -1% +11% +2% +5% +2% +10% +9% +36% -5% +22% +8% +8% +5% +4% +4% +0% +87% +4% +2% +9% -12% +8% +15% +11% -1% +30% -4% +5% +80% +70% -4% % Growth +3% +3% +2% +7% -3% +11% -0% -2% -2% +4% +5% -2% WW Market Status Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Phase III Marketed Marketed Marketed Marketed Marketed Marketed Approved Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Filed Marketed Marketed Marketed Marketed Filed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Marketed Phase III 2016 Change vs Apr-10 +27 -257 -141 -116 +848 +266 -355 -439 +5 +569 +1556 +985 +2289 +394 -1067 +330 -189 -210 +330 +848 +163 +11 +28 -763 +166 +324 +268 -171 +869 +151 -278 +308 -105 +804 -387 -135 -195 +137 -175 +70 +208 -42 -1048 +132 -407 -227 +888 +451 -73 +379 +7023 -5849 +1% -7% -4% -3% +35% +10% -11% -14% +0% +29% +174% +70% n/m +22% -34% +20% -9% -10% +23% +96% +11% +1% +2% -34% +13% +30% +25% -12% +207% +13% -18% +33% -8% +193% -24% -10% -14% +14% -14% +7% +24% -4% -50% +15% -29% -18% +807% +84% -7% +62% +9% -2%

insulin glargine recombinant Sanofi etanercept infliximab efavirenz; emtricitabine; tenofovir pneumococcal vaccine pegfilgrastim icosapent ethyl trastuzumab denosumab sipuleucel-T rosuvastatin calcium belimumab glatiramer acetate telaprevir emtricitabine; tenofovir disoproxil fumarate pregabalin botulinum toxin type A epoetin alfa insulin aspart recombinant insulin detemir recombinant Amgen Johnson & Johnson Gilead Sciences Pfizer Amgen Amarin Roche Amgen Dendreon AstraZeneca Human Genome Sciences Teva Pharmaceutical Industries Vertex Pharmaceuticals Gilead Sciences Pfizer Allergan Amgen + J&J Novo Nordisk Novo Nordisk

lisdexamfetamine dimesylate Shire ranibizumab liraglutide recombinant apixaban immune globulin (human) varicella vaccine ezetimibe fingolimod rivaroxaban ticagrelor insulin lispro recombinant raltegravir potassium pemetrexed disodium eptacog alfa estrogens, conjugated abatacept exenatide saxagliptin hydrochloride interferon beta-1a rifaximin bortezomib natalizumab factor VIII (procoagulant) tofacitinib citrate Roche Novo Nordisk Bristol-Myers Squibb Baxter International Merck & Co Merck & Co Novartis Johnson & Johnson AstraZeneca Eli Lilly Merck & Co Eli Lilly Novo Nordisk Pfizer Bristol-Myers Squibb Amylin + Eli Lilly Bristol-Myers Squibb Biogen Idec Salix Pharmaceuticals Takeda Elan Baxter International Pfizer

Total Total USA Individual Products Forecast in EvaluatePharma

Source: EvaluatePharma (25 MAY 2011) Note: Sales represent company reported sales where available, otherwise based on an average of equity analyst estimates.

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

20

Worldwide Rx & OTC Sales by Therapy Area in 2010


Oncology Segment Largest Segment in 2010 EvaluatePharma found that sales from products within the oncology therapeutic category grew by 6% in 2010 to $60.0bn, maintaining its lead over anti-hypertensives as the largest therapeutic category. 2009's fastest growing category, anti-virals, saw the biggest decline amongst the top 15 categories, as sales fell by 11% to $22.1bn. This decline was driven by a sharp drop in sales of GSK's Valtrex following patent expiration in December 2009, as well as a decline in H1N1 (swine flu) treatments following stockpiling in 2009.

Analysis on Top 10 Therapy Sales in 2010, Market Share & Sales Growth (2009-10)
Source: EvaluatePharma (25 MAY 2011)
WW Market Share %

12%

10% Oncology

Key Drivers Avastin (Roche) Alimta (Lilly) Revlimid (Celgene) Patent Expiries Eloxatin (Sanofi) Arimidex (AZN)

8%

Key Growth Breaks (H1N1) Tamiflu (Roche) Relenza (GSK)

6%

Anti-hypertensives Bronchodilators Anti-diabetics Anti-hyperlipidaemics Anti-virals Antacids and Antiulcerants Anti-psychotics Vaccines

Anti-rheumatics

4%

2%

Key Drivers Humira (Abbott) Enbrel (Amgen/Pfizer) Remicade (J&J/ Merck)

0% -15% -10% -5% +0% +5% +10% +15%


% Sales Growth: 2009-10

+20%

WW Rx & OTC Sales by Therapy Area: Top 15 Categories Therapy Area


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Oncology Anti-hypertensives Bronchodilators Anti-rheumatics Anti-diabetics Anti-hyperlipidaemics Vaccines Anti-virals Anti-psychotics Antacids and Anti-ulcerants Anti-bacterials Sensory organs Antidepressants Platelet aggregation inhibitors Dermatologicals Top 15 Other Total WW Rx & OTC Sales 2009
56.4 42.0 30.9 29.0 27.4 29.3 23.4 24.7 18.3 17.7 16.1 12.4 13.9 12.8 11.1 365.3 322.3 687.5

WW Sales ($bn) 2010 % Growth


60.0 40.9 32.8 32.7 30.6 29.8 25.3 22.1 19.2 16.9 15.4 13.8 13.7 12.6 12.4 378.0 329.1 707.1 +6% -2% +6% +13% +12% +2% +8% -11% +5% -5% -5% +12% -1% -2% +11% +3.5% +2.1% +2.8%

2009
8.2% 6.1% 4.5% 4.2% 4.0% 4.3% 3.4% 3.6% 2.7% 2.6% 2.3% 1.8% 2.0% 1.9% 1.6% 53.1% 46.9% 100.0%

WW Market Share 2010 Chg. (+/-)


8.5% 5.8% 4.6% 4.6% 4.3% 4.2% 3.6% 3.1% 2.7% 2.4% 2.2% 2.0% 1.9% 1.8% 1.7% 53.5% 46.5% 100.0% +0.3% -0.3% +0.1% +0.4% +0.3% -0.0% +0.2% -0.5% +0.0% -0.2% -0.2% +0.2% -0.1% -0.1% +0.1% +0.3% -0.3% +194.6

Rank Chg. (+/-)


+1 +1 -1 +1 -1 +2 -1 -1 -

Total 'Rx & OTC Sales' includes:


WW Unbranded Generic Sales OTC Pharmaceuticals
54.1 30.9 61.2 31.9 +13.2% +3.3% 7.9% 4.5% 8.7% 4.5% +0.8% +0.0%

Note: Industry sales based on Top 500 pharmaceutical and biotech companies. Sales in 2010 based on company reported data.

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

21

Worldwide Prescription Drug Sales in 2010


GSK Out of Top 5; First Time Since Late 1980s. Pfizer Maintain No.1 Positions EvaluatePharma found that GSK dropped out of the World's Top 5 companies in 2010, based on booked end-user prescription drug sales, which represents the first time GSK has been out of the top 5* since the late 1980s. GSK sales declined 2% to $35.6bn in 2010. Pfizer maintained its number one position, in terms of worldwide prescription drug sales, as it benefited from the first full year of consolidating Wyeth, acquired in October 2009. Teva continues to rise up the ranking from 15th to 13th in the World. Sanofi was the worst performing global major, recording a 4% decline in worldwide prescription drug sales as it was hit by generic competition on Lovenox, Eloxatin, Plavix and Allegra. In 2010, despite the decline in sales of vaccines and treatments for swine flu in 2010, prescription drug sales growth increased to 2.9% in 2010 vs. 2.5% in 2009.
Global Ranking on WW Prescription Drug Sales in 2010 Source: EvaluatePharma (25 MAY 2011)
WW Prescription Sales ($bn) 60 50 40 30 20 10 0 Pfizer**
+1 +4 -2 -2 -1 54.1 28% 41.4 12% 40.4 45% 36.6 -4% 35.6 -1% 35.6 32.1 -2% +1% 20.8 +6% +1 20.7 -2% -1 19.9 +21% Sales ($bn) Growth rate % Ranking Chg. 2009-10

Merck & Co**

Eli Lilly

Roche

GlaxoSmithKline

AstraZeneca

Johnson & Johnson

Novartis

Sanofi

WW Prescription Sales in 2010: Top 20 Companies


Company Pfizer** Novartis Merck & Co** Sanofi Roche GlaxoSmithKline AstraZeneca Eli Lilly Johnson & Johnson Abbott Laboratories** Bristol-Myers Squibb Amgen Teva Pharmaceutical Industries Bayer Boehringer Ingelheim Takeda Novo Nordisk Daiichi Sankyo Astellas Pharma Baxter International Total Top 20 Other Total WW Prescription Sales ($bn) 2009 2010 % Growth
42.4 37.0 27.8 38.3 36.0 36.3 31.6 19.7 21.2 16.5 14.8 14.4 12.5 14.3 13.8 11.9 9.6 9.2 9.7 7.8 424.7 231.4 656.1 54.1 41.4 40.4 36.6 35.6 35.6 32.1 20.8 20.7 19.9 15.5 14.7 14.5 14.2 12.6 12.6 10.8 10.8 10.3 8.1 461.1 213.7 674.8 +28% +12% +45% -4% -1% -2% +1% +6% -2% +21% +5% +2% +16% -0% -9% +5% +13% +17% +6% +4% +9% -8% +2.9%

2009
6.5% 5.6% 4.2% 5.8% 5.5% 5.5% 4.8% 3.0% 3.2% 2.5% 2.3% 2.2% 1.9% 2.2% 2.1% 1.8% 1.5% 1.4% 1.5% 1.2% 64.7% 35.3% 100.0%

WW Market Share 2010 Chg. (+/-)


8.0% 6.1% 6.0% 5.4% 5.3% 5.3% 4.7% 3.1% 3.1% 2.9% 2.3% 2.2% 2.1% 2.1% 1.9% 1.9% 1.6% 1.6% 1.5% 1.2% 68.3% 31.7% 100.0% +1.6% +0.5% +1.8% -0.4% -0.2% -0.3% -0.1% +0.1% -0.2% +0.4% +0.0% -0.0% +0.2% -0.1% -0.2% +0.0% +0.1% +0.2% +0.0% +0.0% +3.6%

Rank Chg. (+/-)


+1 +4 -2 -2 -1 +1 -1 +2 -1 -1 +1 +1 -2 -

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Source: EvaluatePharma (25 MAY 2011) Note: Sales in 2010 based on company reported data. Excludes alliance revenue and royalties where possible. *GSK and Glaxo have consistently been in the Top 5 since late 1980s. **Abbott, Merck & Co and Pfizer based on reported data for 2009/10, not pro-forma. (Abbott acquired Solvay Pharmaceuticals in Feb 2010, Merck & Co acquired Schering-Plough in Nov 2009 and Pfizer acquired Wyeth in Oct 2009.) Copyright 2011 EvaluatePharma Ltd. All rights reserved. 22

Abbott Laboratories**

Worldwide Generic Drug Sales in 2010


Teva Dominates Generic Segment in 2010; Generic Market Expands 13%* EvaluatePharma found that Teva Pharmaceutical continued to dominate the rapidly expanding generic drug market in 2010 with a global market share of 18%. Teva benefited from the consolidation of sales from its $5.3bn acquisition of German generics company ratiopharm, in August 2010. Sanofi experienced strong growth of 44% in 2010 as it benefited from the first full year consolidation of sales from its acquisitions of Zentiva, Medley and Kendrick in 2009. Overall the generic drug market expanded 13% in 2010 based on EvaluatePharma coverage*. Global Ranking on WW Generic Drug Sales in 2010 Source: EvaluatePharma (25 MAY 2011)
WW Generic Sales ($bn) 12 11 10 9 8 7 6 5 4 3 2 1 0 Teva Pharmaceutical Industries Mylan Novartis Actavis 11.0
+17% Sales ($bn) Growth rate % Ranking Chg. 2009-10

7.7
15%

5.0
+6% +5% +38% +12% +44% +27% +55% -5%

2.6

2.3
+2

2.0 Hospira

2.0
+3

2.0 Daiichi Sankyo

1.8
+2

1.5
-1

Watson Pharmaceuticals

Aspen Pharmacare

WW Unbranded Generic Drug Sales in 2010: Top 20 Companies


WW Generic Sales ($bn) 2009 2010 % Growth
9.4 6.7 4.7 2.4 1.6 1.8 1.4 1.6 1.2 1.6 1.0 0.8 1.0 2.3 0.9 1.1 1.0 0.8 0.8 1.1 43.3 10.7 54.1 11.0 7.7 5.0 2.6 2.3 2.0 2.0 2.0 1.8 1.5 1.3 1.2 1.2 1.2 1.1 1.1 1.1 1.1 0.9 0.9 48.9 12.3 61.2 +17% +15% +6% +5% +38% +12% +44% +27% +55% -5% +21% +45% +19% -49% +29% -0% +14% +24% +8% -19% +13% +14% +13%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Company Teva Pharmaceutical Industries Novartis Mylan Actavis Watson Pharmaceuticals Hospira Sanofi Daiichi Sankyo Aspen Pharmacare STADA Arzneimittel Apotex Sun Pharmaceutical Industries Cipla ratiopharm Fresenius Krka Dr. Reddy's Laboratories Lupin Abdi Ibrahim Par Pharmaceutical Companies Total Top 20 Other Total

2009
17.4% 12.3% 8.7% 4.5% 3.0% 3.4% 2.6% 2.9% 2.2% 2.9% 1.9% 1.6% 1.9% 4.3% 1.6% 2.0% 1.8% 1.6% 1.5% 2.0% 80.2% 19.8% 100.0%

WW Market Share 2010 Chg. (+/-)


18.0% 12.5% 8.2% 4.2% 3.7% 3.3% 3.3% 3.3% 3.0% 2.4% 2.1% 2.0% 2.0% 1.9% 1.9% 1.8% 1.8% 1.7% 1.5% 1.4% 79.9% 20.1% 100.0% +0.6% +0.2% -0.5% -0.3% +0.7% -0.0% +0.7% +0.4% +0.8% -0.5% +0.1% +0.4% +0.1% -2.4% +0.2% -0.2% +0.0% +0.1% -0.1% -0.6% -0.2%

Source: EvaluatePharma (25 MAY 2011) Note: Sales in 2010 based on company reported data. ratiopharm sales for 2010 reflect the period January 2010 to August 2010, when the company was acquired by Teva. Abdi Ibrahim, Actavis, Apotex, Aspen, Cipla, Dr. Reddy's, Lupin, and Sun based on forecast data for 2010. *EvaluatePharma coverage: 66 generic companies. Copyright 2011 EvaluatePharma Ltd. All rights reserved. 23

STADA Arzneimittel Rank Chg. (+/-)


+2 +3 +2 -1 +3 +7 +2 -9 +2 -4 -1 +1 -7

Sanofi

M&A Analysis: 2006 to 2010


M&A Deal Value Slumps in 2010, Following Bumper 2009 EvaluatePharma found that total deal values from M&A involving pharmaceutical companies declined by 60% to $75bn in 2010, compared to $188bn in 2009, which was a bumper year for M&A with 3 mega-mergers completed; Pfizer-Wyeth, Merck-Schering-Plough and Roche-Genentech. The number of deals increased marginally (+5%) to 152 deals closing in 2010. The biggest deal of the year was Novartis acquiring a majority stake in Alcon for $28.1bn. This followed an acquisition of a minority stake back in 2008. 2010 also saw further consolidation in the generic sector, with Teva acquiring ratiopharm, Endo acquiring Qualitest, Cephalon acquiring Mepha and Mylan acquiring Bioniche Pharma.
Count of Pharma M&A Deals vs. Total Pharma M&A Value (2005 - 2009) (2006 2010) Source: EvaluatePharma (30 APR 2010) (25 MAY 2011)
350
2005 2006 FUJ [YAM] ($20.8bn) SCH [BAY] ($21.3bn) PFE Cons [JNJ] ($16.6bn) SAN [DAI] ($15.4bn) 2008 2007 Alcon [NVS] ($10.4bn) Organon [SGP] ($15.6bn) MEDI [AZN] ($15.6bn) Serono [Merck] ($13.8bn) 2010 2009 Alcon [NVS] ($28.1bn) WYE [PFE] ($68.0bn) DNA [Roche] ($46.8bn) SGP [MRK] ($41.1bn) Target [Acquiror] (Deal Value)

300

300

250

Deal Value ($bn) Deal Value ($bn)

250

200

153 150 124 134

145

152

150

100

173% Growth

100

50 $101bn 0 2006 2007 2008


Deal Value Deal Count

50 $86bn $69bn $188bn 2009 $75bn 0 2010

Count of Pharma M&A Deals vs. Total Pharma M&A Value (2006 - 2010)
Year Deal Count % Chg. Deal Value ($bn) % Chg. 2006
124 101

2007
134 8% 86 -15%

2008
153 14% 69 -20%

2009
145 -5% 188 171%

2010
152 5% 75 -60%

Top 10 M&A Deals in 2010: Ranked on Deal Value


Target 1 2 3 4 5 6 7 8 9 10 Target Location USA Belgium Germany USA USA India USA USA USA Japan Target Focus Specialty Regional Major Generic Specialty Biotechnology Generic Specialty Specialty Generic Regional Major Acquiror Novartis Abbott Laboratories Teva Biovail Astellas Pharma Abbott Laboratories Celgene Sanofi Endo Pharmaceuticals Boehringer Ingelheim Completion Deal Date Value ($bn) 26 Aug 10 28.1 15 Feb 10 6.6 10 Aug 10 5.0 28 Sep 10 4.5 09 Jun 10 4.0 08 Sep 10 3.8 15 Oct 10 2.9 09 Feb 10 1.9 01 Dec 10 1.2 14 Apr 10 0.8 15.9 74.6

Alcon Solvay Pharma ratiopharm Valeant OSI Pharmaceuticals Piramal (Solutions) Abraxis BioScience Chattem Qualitest SSP Other Total Source: EvaluatePharma (25 MAY 2011)

Note: Analysis based on closing date of deal.

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

Deal Count Deal Count

2007 2006 Organon [SGP] ($15.6bn) SCH [BAY] ($21.3bn) MEDI [AZN] ($15.6bn) PFE Cons [JNJ] ($16.6bn) Serono [Merck] ($13.8bn)

2009 WYE [PFE] ($68.0bn) 2008 DNA [Roche] ($10.4bn) Alcon [NVS] ($46.8bn) SGP [MRK] ($41.1bn)

200

24

Venture Financing Analysis: 2006 to 2010 New Analysis


Venture Financing Deals Fall in 2010 EvaluatePharma found that in 2010 both the number of venture financing deals, down 10% to 298, and the total deal value, down 7% to $4.9bn, fell vs. 2009. The value of venture financing deals can be viewed as a indicator of R&D investment in the private Biotech sector. At $4.9bn it represents a mere 4% of the total pharmaceutical R&D spend of $127bn. The trend in venture financing has been flat for the last 3 years. Of the top 10 venture financing deals in 2010, 7 were for US-based companies, with the biggest being Alvogen, a company focused on the development of complex generics, which raised $200m in November 2010.
Count of Venture Financing Deals vs. Total Venture Financing Value (2006 - 2010) Source: EvaluatePharma (25 MAY 2011)
7000 700

6000

$6,210m $5,604m

600

Deal Value ($m)

5000

$5,251m $4,893m $4,909m

500

4000 333 3000 286 291 330 298

400

300

2000

200

1000

100

0 2006 2007 2008


Deal Value Deal Count

0 2009 2010

Count of Pharma Venture Financing Deals vs. Total Pharma Venture Financing Value (2006 - 2010)
Year Deal Count % Chg. Deal Value ($m) % Chg. 2006
286 5,604

2007
333 16% 6,210 11%

2008
291 -13% 4,893 -21%

2009
330 13% 5,251 7%

2010
298 -10% 4,909 -7%

Top 10 Venture Financing Deals in 2010: Ranked on Deal Value


Company 1 2 3 4 5 6 7 8 9 10 Listed / Private Private Listed Listed Private Private Private Private Private Private Private Country Company Type USA Generic USA Biotechnology USA Biotechnology UK Biotechnology USA Biotechnology Germany Biotechnology USA Biotechnology Germany Biotechnology USA Specialty USA Biotechnology Financing Round Undisclosed PIPE PIPE Undisclosed Series G Series B Series B Series C Series C Series A Date 19 Nov 10 19 Mar 10 29 Nov 10 02 Mar 10 12 Jul 10 14 Apr 10 13 Sep 10 21 Sep 10 19 Oct 10 26 May 10 Deal Value ($m) 200 181 129 100 78 75 70 70 69 60 3,877 4,909

Alvogen Group Lexicon Pharmaceuticals Theravance Archimedes Pharma Reata Pharmaceuticals AiCuris Relypsa immatics biotechnologies Pearl Therapeutics TESARO Other Total Source: EvaluatePharma (25 MAY 2011)

Note: Includes investments in pharmaceutical and biotech companies only. Does not include genomics or medical devices companies. Includes Private Investment in Public Equity (PIPE).

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

Deal Count

25

Key Product Events Positively Impacting Shareholder Value in 2010 New Analysis
Crestor Ruling Largest Positive Event in 2010 The analysis below highlights the top 15 product events which positively impacted shareholder value on the day of announcement (measured by change in market capitalization) in 2010. The largest event was a US court ruling on Crestor, which removed the threat of generics prior to 2016. This event initially added $5.8bn in value, +9% share price gain, to AstraZeneca. The approval of Prolia (denosumab) was the second biggest event, adding $5.1bn to the market cap. of Amgen, reflecting a 11% share price gain.
Product
Crestor

Company
1 AstraZeneca

Event Type
Litigation

Therapy Area
Anti-hyperlipidaemics

Date

Commentary on Share Price Change

% Share Market Cap Price Change Change


+9% +5,760

29 Jun 10 29 Jun: A US court rules that the patent on the company's cholesterol-lowering drug Crestor is valid, removing the threat of generic versions of the drug entering the US market until the patent expires in 2016.

2 Amgen

FDA Approval (PDUFA)

Prolia

Bone calcium regulators 02 Jun 10 1 Jun [post market]: Company receives FDA approval for its key growth driver, osteoporosis drug Prolia, nearly two months ahead of the expected action date of 25 Jul. Anti-coagulants 11 Jun 10 10 Jun [post-market]: Company and partner BristolMyers Squibb end phase III trial of anti-coagulant drug apixaban early, after clear efficacy is seen in a trial attempting to demonstrate a lower risk of stroke in patients with atrial fibrillation. 18 Mar 10 18 Mar: Shares rise on news that Novartis' generics division, Sandoz, has returned the US rights to lung drug, VR315, a potential generic competitor to GlaxoSmithKline's asthma drug, Advair, back to Vectura, due to potential difficulties in getting the drug to market in the US. 20 Oct 10 20 Oct: Shares rise following the FDA's complete response letter for Amylin's diabetes drug, Bydureon, a potential competitor for Novo Nordisk's diabetes treatment, Victoza, which received FDA approval in January. 23 Apr 10 23 Apr: A US federal court rules in the company's favour in a patent lawsuit with Teva over acid reflux drug, Protonix, stating that Pfizer's patent is valid and has been infringed by Teva. 09 Dec 10 9 Dec: Company and partner Active Biotech announce positive headline data from first of two phase III trials for their oral MS drug, laquinimod, meeting primary and secondary efficacy endpoints as well as demonstrating a comparable safety profile to placebo. 24 Sep 10 24 Sep: The CHMP issues rival Merck KGaA with a negative opinion for its oral MS treatment, cladribine, stating that the drug's benefits do not outweigh its risks.

+11%

+5,106

3 Pfizer

Phase III Trial Results

Eliquis

+4%

+4,436

4 GlaxoSmithKline

Competitor Announcement

Advair

Other bronchodilators

+4%

+4,003

5 Novo Nordisk

Competitor Announcement

Victoza

Anti-diabetics

+9%

+3,834

6 Pfizer

Litigation

Protonix

Antacids & antiulcerants

+3%

+3,470

7 Teva

Phase III Trial Results

Laquinimod MS Therapies

+7%

+3,145

8 Novartis

Competitor Announcement

Gilenya

MS Therapies

+2%

+2,708

9 Amgen

Phase III Trial Results

Xgeva

Bone calcium regulators 14 Dec 10 13 Dec [post market]: Top-line phase III results for the company's bone drug, Xgeva (denosumab), demonstrate that the drug significantly improved median bone metastasis-free survival by 4.2 months compared to placebo. Anti-neoplastic MAbs 07 Jun 10 7 Jun: Phase III trial results for company's melanoma treatment, ipilimumab, presented at ASCO on 5 Jun, show that the drug prolongs life and survival of patients by 34%. 17 Nov 10 16 Nov: An FDA advisory panel votes 13 to 2 in favour of approving company and partner, Human Genome Sciences' lupus drug, Benlysta; final FDA decision due on 9 Dec. 15 Nov 10 15 Nov: Company and partner, Johnson & Johnson, report phase III data for anti-clotting drug, Xarelto, which show that the drug is better at preventing stroke than standard treatment, warfarin, with lower risk of intracranial bleeding. 12 Aug 10 11 Aug [post market]: An FDA advisory panel unanimously recommends approval of the company and partner Valeant Pharmaceuticals' epilepsy drug, ezogabine (Potiga); final FDA decision due by 30 Aug. 28 Jul 10 28 Jul: An FDA advisory panel votes 7-1 in favour of recommending approval for the company's blood thinner, Brilinta; final FDA decision due by 16 Sep. 06 Jul 10 6 Jul: Shares likely to remain volatile ahead of FDA meetings on 13-14 July to review cardiovascular safety issues for Avandia.

+5%

+2,506

10 Bristol-Myers

Phase III Trial Results

Yervoy

+6%

+2,442

11 GlaxoSmithKline

FDA Advisory Committee

Benlysta

Immunosuppressants

+2%

+2,389

12 Bayer

Phase III Trial Results

Xarelto

Anti-coagulants

+4%

+2,372

13 GlaxoSmithKline

Broker Upgrade

Potiga

Anti-epileptics

+3%

+2,322

14 AstraZeneca

FDA Advisory Committee FDA Advisory Committee

Brilinta

Platelet aggregation inhibitors Anti-diabetics

+3%

+2,274

15 GlaxoSmithKline

Avandia

+3%

+2,229

Top 15 Total Total Events Positively Impacting Shareholder Value in 2010

+48,996 +366,102

Source: EvaluatePharma's EventAnalyzer (25 MAY 2011) Note: EvaluatePharma's EventAnalyzer contains a back catalogue of events which had the greatest impact on company valuations dating back to December 2007. Events can be viewed by Company, Product, Therapy Area and Peer Group to see instantly the impact of events on company valuation and the news flow driving share price movement. Events are categorized into 100 unique Event Type classifications, allowing you to track the market impact of key types of news flow (e.g. regulatory approvals, financial results, patent litigation, broker sentiment and competitor announcements, etc).

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

26

Key Product Events Negatively Impacting Shareholder Value in 2010 New Analysis
Avastin Hit by Double Setback in 2010 The analysis below highlights the largest 15 product events negatively impacting shareholder value on the day of announcement (measured by change in market capitalization) in 2010. The largest two events both relate to Roche's Avastin, which saw its consensus forecast tumble over the year following negative PIII results in prostate cancer and a negative opinion from an FDA Advisory Committee on breast cancer. Together these events wiped $9.2bn off Roche's market cap., a 7% decline in its share price.
% Share Market Cap Price Change Change
-+3% -+4,724

Company
1 Roche

Event Type
Phase III Trial Results

Product
Avastin

Therapy Area
Anti-neoplastic MAbs

Date

Commentary on Share Price Change

12 Mar 10 12 Mar: Avastin (bevacizumab) fails to meet its primary phase III endpoint of extending overall survival in prostate cancer patients, compared with chemotherapy and prednisone alone. 21 Jul 10 20 Jul [post market]: An FDA advisory panel votes 121 in favour of revoking Avastin's approval for breast cancer, stating that studies show insufficient benefit for patients; final FDA decision due 17 Sep. 23 Jul 10 23 Jul: Momenta Pharmaceuticals receives FDA approval for its generic version of Sanofi' blood thinner, Lovenox, raising fears that the FDA may soon approve a generic version of Copaxone; Momenta confirms in a conference call that it is working with the FDA on its Copaxone application. 21 Apr 10 21 Apr: Bloomberg reports that UnitedHealth Group, the US' biggest medical insurer by sales, plans to double the amount it will charge for companys cholesterol pills, Vytorin and Zetia, from 1 Jul, raising concerns that the move will deter patients from using the medicines. 17 Dec 10 16 Dec [post market]: Company receives an FDA complete response letter for its heart drug, Brilinta, requesting further analyses of phase III trial data, but not additional clinical studies, potentially delaying US approval of the drug by a further nine months. 18 Jun 10 18 Jun: Company announces the implementation of a risk mitigation plan in its phase III programme for diabetes drug, taspoglutide, following cases of hypersensitivity in patients, leading to a potential delay in filing of at least 12-18 months.

2 Roche

FDA Advisory Committee

Avastin

Anti-neoplastic MAbs

-+4%

-+4,500

3 Teva

Competitor Announcement

Copaxone

MS Therapies

-+9%

-+4,323

4 Merck & Co

Pricing Issues

Vytorin

Anti-hyperlipidaemics

-+4%

-+4,115

5 AstraZeneca

Complete Response Letter

Brilinta

Platelet aggregation inhibitors

-+6%

-+4,023

6 Roche

Phase III Trial Results

Taspoglutide Anti-diabetics

-+2%

-+3,490

7 Pfizer

Product Suspended

Tanezumab

Non-narcotic analgesics 24 Jun 10 23 Jun [post market]: Company suspends phase III trials of its osteoarthritis drug, tanezumab, after some patients taking the drug experienced a worsening of their condition that required joint replacement surgery. Anti-coagulants 23 Jul 10 23 Jul: Company cuts its 2010 financial outlook after Momenta Pharmaceuticals receives FDA approval for its generic version of Lovenox. 22 Apr 10 Shares continue to fall after Bloomberg reported on 21 Apr that UnitedHealth Group, the US' biggest medical insurer by sales, plans to double the amount it will charge for Vytorin and Zetia from 1 Jul, raising concerns that the move will deter patients from using the medicines. 13 May 10 13 May: Mylan files for FDA approval of its generic version of Pfizer's cancer drug, Sutent, challenging several patents on the drug which expire in 2021. 22 Feb 10 22 Feb: The FDA begins reviewing data on possible heart risks linked to Avandia following the release of FDA documents on 20 Feb which included a 2008 memo from FDA drug safety reviewers who recommended withdrawing the drug from the US market due to safety concerns. 18 Jun 10 18 Jun: A new study published in the Diabetes Care journal suggests that company's diabetes drug, Lantus, raises the risk of cancer versus other insulins. 03 May 10 3 May: German newspaper Handelsblatt, states that the company's cancer drug, Avastin, is only marginally effective and has significant toxicity. 30 Jun 10 Shares fall back slightly after rising 9% on 29 Jun after a US court rules that the patent on Crestor is valid, removing the threat of generic versions of the drug entering the US market until the patent expires in 2016. 18 Oct 10 18 Oct: Shares fall on news that Pfizer has signed a deal with Biocon to sell its biosimilar versions of insulin, which will compete with Novo's brands, Novolin and Novolog.

-+3%

-+3,388

8 Sanofi

New Company Financial Guidance Pricing Issues

Lovenox

-+4%

-+3,323

9 Merck & Co

Vytorin

Anti-hyperlipidaemics

-+3%

-+3,024

10 Pfizer

FDA Filing

Sutent

Anti-angiogenics

-+2%

-+2,743

11 GlaxoSmithKline

Safety Concerns Avandia

Anti-diabetics

-+3%

-+2,713

12 Sanofi

Side Effect Risk/ Lantus Negative Label Side Effect Risk/ Avastin Negative Label Litigation Crestor

Anti-diabetics

-+3%

-+2,707

13 Roche

Anti-neoplastic MAbs

-+2%

-+2,487

14 AstraZeneca

Anti-hyperlipidaemics

-+3%

-+2,350

15 Novo Nordisk

Competitor Announcement

Novolin

Anti-diabetics

-+5%

-+2,343

Top 15 Total Total Events Positively Impacting Shareholder Value in 2010

-+50,253 -+321,620

Source: EvaluatePharma's EventAnalyzer (25 MAY 2011) Note: EvaluatePharma's EventAnalyzer contains a back catalogue of events which had the greatest impact on company valuations dating back to December 2007. Events can be viewed by Company, Product, Therapy Area and Peer Group to see instantly the impact of events on company valuation and the news flow driving share price movement. Events are categorized into 100 unique Event Type classifications, allowing you to track the market impact of key types of news flow (e.g. regulatory approvals, financial results, patent litigation, broker sentiment and competitor announcements, etc).

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

27

Enterprise Value Analysis: 2009 to 2010


Johnson & Johnson Maintains No.1 Position in Enterprise Value Rankings in 2010 EvaluatePharma found that despite losing 7% of its value in 2010 Johnson & Johnson retained its No.1 ranking in terms of enterprise value in 2010, with a valuation of $159bn. Novo Nordisk demonstrated an impressive 59% increase in enterprise value and 70% increase in share price following approval of Victoza, positive pipeline developments for Degludec, clinical setbacks for potential competitor taspoglutide and safety scares for Sanofis long-acting insulin, Lantus. Roche's enterprise value fell 16% to $142bn, primarily on setbacks to Avastin and taspoglutide. Global Ranking on Enterprise Value in 2010 Source: EvaluatePharma (31 DEC 2010)
180 160 140
$158bn $156bn $150bn $142bn +80% +70% $135bn $114bn $85bn $85bn $71bn $61bn

+70%

+60% +50% +40% +30% +20% +10% +0%

120 100 80 60 40 20 0

+12% -3% -2% -17% GlaxoSmithKline Johnson & Johnson Roche Pfizer Merck & Co Novartis -0% -10% -17% Abbott Laboratories Sanofi Bayer Novo Nordisk -11% -10%

-10% -20% -30%

Top 20 Companies in 2010: Ranked by Enterprise Value (based on valuation on 31 DEC 10)
Enterprise Value ($bn) 2009 2010 % Growth
171.0 166.6 115.6 168.8 136.7 124.0 105.5 89.1 81.9 38.6 65.7 53.0 53.4 46.4 39.0 40.6 42.1 36.6 38.4 26.3 1,639.3 158.5 156.4 149.8 141.7 134.6 114.4 85.3 85.0 71.1 61.3 58.2 52.4 47.1 46.2 43.1 42.7 40.6 31.0 30.5 28.1 1,577.7 -7% -6% +30% -16% -2% -8% -19% -5% -13% +59% -11% -1% -12% -1% +10% +5% -4% -15% -21% +7% -4%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Company Johnson & Johnson Pfizer Novartis Roche Merck & Co GlaxoSmithKline Sanofi Abbott Laboratories Bayer Novo Nordisk AstraZeneca Teva Pharmaceutical Amgen Alcon Reckitt Benckiser Bristol-Myers Squibb Eli Lilly Baxter International Gilead Sciences Takeda Total Top 20

Share Price ($ ADR) 2009 2010 % Growth


63.92 17.83 52.48 170.66 36.16 42.25 39.27 53.15 79.80 63.85 46.94 55.81 56.57 164.35 54.48 24.95 34.72 58.39 43.27 45.35 61.85 17.51 58.95 141.50 36.04 39.22 32.23 47.47 73.36 112.57 46.19 52.13 54.90 163.40 55.01 26.15 35.04 50.62 36.24 48.93 avg. -3% -2% +12% -17% -0% -10% -17% -11% -10% +70% -4% -7% -3% -1% +1% +5% +1% -13% -16% +8% -1%

Enterprise Value Ranking 2009 2010 Chg. (+/-)


1 3 6 2 4 5 7 8 9 17 10 12 11 13 16 15 14 19 18 20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 +1 +3 -2 -1 -1 +7 -1 -2 -1 +1 -1 -3 +1 -1 -

Source: EvaluatePharma (31 DEC 2010)

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

Share Price Performance (%)

Market Cap ($bn)

28

Net Income in 2010: Top 20 Companies


Pfizer No. 1 in Terms of Net Income in 2010 EvaluatePharma found that Pfizer reported the industrys largest net income (normalised) in 2010, recording $18bn. Of the Top 20 Teva recorded the largest improvement in net margin, up 3.9% to 25.6%, whilst benefiting from one of the lowest tax rates. GlaxoSmithKline's net income (normalised) fell 23% to $7.3bn, with the net margin falling 4.8% to 16.7%. Global Ranking on Net Income Normalised: Top 10 Companies Source: EvaluatePharma (25 MAY 2011)
Net Income ($bn)
20 18 16 14 12 10 8 6 4 2 0
Net income normalised ($bn) Growth rate %

18.0
+27% +27%

13.3
+3%

12.2
+2%

11.8
+24% +13%

10.7
+45% +45%

10.5
+7%

9.6
+5%

7.3
-23%

6.5
+12%

5.2
+8%

Pfizer*

GlaxoSmithKline

AstraZeneca

Roche

Merck & Co*

Johnson & Johnson

Novartis

Net Income in 2010: Top 20 Companies


Net Income Normalised ($bn) 2009 2010 % Growth
14.2 12.9 12.0 9.5 7.4 9.8 9.2 9.5 5.8 4.9 4.9 4.2 3.0 3.6 2.7 3.9 2.2 2.0 2.3 2.1 126.1 18.0 13.3 12.2 11.8 10.7 10.5 9.6 7.3 6.5 5.2 4.9 4.6 4.1 3.7 3.1 2.9 2.6 2.6 2.4 2.1 138.2 +27% +3% +2% +24% +45% +7% +5% -23% +12% +8% +0% +10% +36% +4% +13% -24% +16% +27% +2% +2% +10% Net Margin

Company 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Pfizer* Johnson & Johnson Sanofi Novartis Merck & Co* Roche AstraZeneca GlaxoSmithKline Abbott Laboratories* Eli Lilly Amgen Bayer Teva Pharmaceutical Industries Bristol-Myers Squibb Gilead Sciences Takeda Reckitt Benckiser Novo Nordisk Baxter International Alcon Top 20

2009
28.4% 20.9% 29.4% 21.0% 27.0% 21.7% 27.9% 21.4% 18.9% 22.2% 33.5% 9.6% 21.8% 19.1% 38.8% 24.5% 18.3% 21.1% 18.5% 31.6% 23.8%

2010
26.5% 21.6% 30.3% 22.8% 23.3% 23.1% 29.0% 16.7% 18.5% 22.7% 32.6% 9.9% 25.6% 19.2% 38.7% 17.7% 19.6% 23.7% 18.2% 29.0% 23.4%

Abbott Laboratories*

Chg. (+/-)
-1.9% +0.7% +0.9% +1.9% -3.7% +1.4% +1.1% -4.8% -0.4% +0.5% -0.9% +0.2% +3.9% +0.0% -0.2% -6.8% +1.4% +2.6% -0.4% -2.6% Average

Source: EvaluatePharma (25 MAY 2011) Measure: Net Income Normalised The accounting profit a company made during 2010, adjusted to exclude any one-off items, such as restructuring charges and disposal gains/ losses. *Abbott, Merck & Co and Pfizer based on reported data for 2009/10, not pro-forma.

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

Eli Lilly

Sanofi

29

Net Income Margin in 2010: Top 20 Companies


PDL BioPharma Continues to be the Most Profitable Pharma-Biotech Company in 2010 EvaluatePharma found that for the third year running PDL BioPharma achieved the highest net income normalised margin at 48.8% in 2010, based on a net income of $168m and royalty revenues of $345m. PDL is the first company to spin-out its R&D unit (Facet Biotech) and effectively be run as listed royalty company, with no active R&D operations. Global Ranking on Net Income Margin in 2010: Top 10 Companies Source: EvaluatePharma (25 MAY 2011)

Net Margin %

60% 50%

49% 40% 39% 30% 20% 10% 0% Valeant Pharmaceuticals Gilead Sciences PDL BioPharma Sun Pharmaceutical Warner Chilcott Forest Laboratories ViroPharma Celgene Amgen Sanofi 36% 34% 33%

31%

31%

30%

30%

29%

Net Margin in 2010: Top 20 Companies


Net Margin

Company

2009

2010

Chg. (+/-)

Net Income - Normalised 2009 2010 % Growth

1 PDL BioPharma 59.3% 48.8% -10.5% 189 168 -10.7% 2 Gilead Sciences 38.8% 38.7% -0.2% 2,724 3,073 +12.8% 3 Valeant Pharmaceuticals 47.1% 35.6% -11.5% 387 421 +8.9% 4 ViroPharma 23.8% 34.1% +10.4% 74 150 +103.2% 5 Amgen 33.5% 32.6% -0.9% 4,899 4,900 +0.0% 6 Celgene 32.2% 31.3% -0.9% 862 1,129 +30.9% 7 Sun Pharmaceutical 34.4% 31.2% -3.1% 283 374 +32.1% 8 Sanofi 29.4% 30.3% +0.9% 12,027 12,229 +1.7% 9 Warner Chilcott 33.1% 29.9% -3.2% 475 890 +87.2% 10 Forest Laboratories 26.0% 29.3% +3.4% 1,067 1,284 +20.3% 11 Alcon 31.6% 29.0% -2.6% 2,051 2,082 +1.5% 12 AstraZeneca 27.9% 29.0% +1.1% 9,159 9,642 +5.3% 13 Biogen Idec 26.8% 27.3% +0.5% 1,175 1,288 +9.6% 14 Pfizer 28.4% 26.5% -1.9% 14,202 17,983 +26.6% 15 Teva Pharmaceutical 21.8% 25.6% +3.9% 3,029 4,134 +36.5% 16 Alexion Pharmaceuticals 20.6% 25.0% +4.4% 80 135 +69.5% 17 Pharmstandard 27.0% 24.0% -3.0% 206 235 +14.0% 18 Endo Pharmaceuticals 22.9% 23.9% +1.0% 334 410 +22.8% 19 Novo Nordisk 21.1% 23.7% +2.6% 2,016 2,566 +27.3% 20 Gedeon Richter 19.1% 23.4% +4.3% 254 311 +22.4% Source: EvaluatePharma (25 MAY 2011) Measure: Net Margin A ratio measuring company profitability based on net income normalised divided by total revenue. Note: Analysis only includes companies with two consecutive years of profit and with 2010 profit in excess of $50m. Sun Pharmaceutical is based on forecast data for 2010.

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2010: Top 50 Selling Products in the World


Lipitor is World's Largest Selling Product in 2010 EvaluatePharma found that global brand sales of Lipitor, primarily sold globally by Pfizer and co-marketed with Astellas in Japan, recorded sales of $12.0bn in 2010, down 6% on $12.7bn in 2009.
WW Product Sales ($bn) Product 1 Lipitor 2 Plavix 3 Seretide/Advair 4 Enbrel 5 Humira 6 Remicade 7 Avastin 8 Diovan 9 Rituxan 10 Crestor 11 Seroquel 12 Singulair 13 Herceptin 14 Zyprexa 15 Nexium 16 Lantus 17 Actos 18 Epogen/Procrit/Eprex 19 Abilify 20 Gleevec/Glivec 21 Aricept 22 Spiriva 23 Lovenox/Clexane 24 Neulasta 25 Januvia/Janumet 26 Cymbalta 27 Lexapro/Cipralex 28 Copaxone 29 Blopress/Atacand 30 Micardis 31 Avapro 32 Lyrica 33 Aranesp 34 Lucentis 35 Atripla 36 Taxotere 37 Symbicort 38 Truvada 39 Celebrex 40 Avonex 41 Human insulin & devices 42 Benicar/Olmetec 43 Revlimid 44 Prevnar 13 45 Zetia 46 Rebif 47 Alimta 48 Cozaar 49 NovoRapid 50 Humalog Total Generic Name atorvastatin calcium clopidogrel bisulfate fluticasone propionate; salmeterol xinafoate etanercept adalimumab infliximab bevacizumab valsartan rituximab rosuvastatin calcium quetiapine fumarate montelukast sodium trastuzumab olanzapine esomeprazole magnesium insulin glargine recombinant pioglitazone hydrochloride epoetin alfa aripiprazole imatinib mesylate donepezil hydrochloride tiotropium bromide monohydrate enoxaparin sodium pegfilgrastim sitagliptin phosphate duloxetine hydrochloride escitalopram oxalate glatiramer acetate candesartan cilexetil telmisartan irbesartan pregabalin darbepoetin alfa ranibizumab efavirenz; emtricitabine; tenofovir docetaxel budesonide; formoterol fumarate dihydrate emtricitabine; tenofovir disoproxil fumarate celecoxib interferon beta-1a insulin recombinant human olmesartan medoxomil lenalidomide pneumococcal vaccine ezetimibe interferon beta-1a pemetrexed disodium losartan potassium insulin aspart recombinant insulin lispro recombinant Company Pfizer + Astellas + Almirall BMS + Sanofi GSK + Almirall + Faes Amgen + Pfizer + Takeda Abbott + Eisai J&J + Merck + Mitsubishi Tanabe Roche Novartis + Ipsen Roche + Biogen Idec AstraZeneca + Shionogi + Chiesi AstraZeneca + Astellas Merck + Kyorin + Sigma-Tau Roche Eli Lilly AstraZeneca Sanofi Takeda + Abbott Pharmacological Class Statin/ HMG CoA reductase inhibitor Platelet ADP antagonist Beta 2 adrenoreceptor agonist & corticosteroid TNFa inhibitor Anti-TNFa MAb Anti-TNFa MAb Anti-VEGF MAb Angiotensin II antagonist Anti-CD20 MAb Statin/ HMG CoA reductase inhibitor 5-HT2 (serotonin) & dopamine D2 antagonist Leukotriene D4 antagonist Anti-HER2 (ErbB-2) MAb Atypical anti-psychotic Proton pump inhibitor (PPI) Insulin PPAR gamma agonist 2009 12,669 9,492 7,920 6,295 5,584 5,923 5,744 6,091 5,620 4,836 5,121 4,985 4,862 4,916 4,959 4,293 4,194 4,963 4,039 3,944 3,913 3,351 4,241 3,355 2,611 3,075 3,403 2,826 2,935 2,959 3,087 2,840 2,930 2,338 2,382 3,034 2,309 2,556 2,575 2,323 2,488 2,363 1,706 2,413 2,142 1,706 3,598 1,825 1,959 195,689 2010 11,968 9,148 8,067 7,257 6,742 6,520 6,214 6,126 6,113 6,106 5,611 5,401 5,221 5,026 4,969 4,658 4,601 4,584 4,279 4,265 3,814 3,799 3,724 3,558 3,503 3,491 3,467 3,300 3,283 3,258 3,119 3,077 2,974 2,935 2,927 2,816 2,760 2,746 2,668 2,518 2,502 2,487 2,469 2,416 2,297 2,214 2,209 2,141 2,120 2,054 209,521 % Growth -6% -4% +2% +15% +21% +10% +8% +1% +9% +26% +10% +8% +7% +2% +0% +9% +10% -8% +6% +8% -3% +13% -12% +6% +34% +14% +2% +17% +12% +10% +1% +8% +2% +26% +23% -7% +20% +7% +4% +8% +1% +5% +45% n/m -5% +3% +29% -41% +16% +5% +7% Products Age (Yrs) 14.3 13.2 12.7 12.6 8.4 12.8 7.2 14.7 13.5 8.3 13.7 13.3 12.7 14.7 10.8 10.9 11.8 22.4 8.5 10.0 14.3 9.0 23.4 9.1 4.7 6.8 9.2 14.4 13.5 12.5 13.7 6.7 9.9 4.9 4.8 15.4 10.7 6.8 12.3 15.0 88.2 9.0 5.4 1.4 8.5 13.4 7.2 16.3 11.7 15.0 12.8 Technology Chiral chemistry Small molecule chemistry Small molecule chemistry Recombinant product Monoclonal antibody Monoclonal antibody Monoclonal antibody Small molecule chemistry Monoclonal antibody Small molecule chemistry Small molecule chemistry Small molecule chemistry Monoclonal antibody Small molecule chemistry Chiral chemistry Recombinant product Small molecule chemistry Recombinant product Small molecule chemistry Small molecule chemistry Small molecule chemistry Small molecule chemistry Small molecule chemistry Recombinant product Small molecule chemistry Small molecule chemistry Chiral chemistry Small molecule chemistry Small molecule chemistry Small molecule chemistry Small molecule chemistry Small molecule chemistry Recombinant product Monoclonal antibody Small molecule chemistry Plant extract Small molecule chemistry Small molecule chemistry Small molecule chemistry Recombinant product Recombinant product Small molecule chemistry Small molecule chemistry Bioengineered vaccine Small molecule chemistry Recombinant product Small molecule chemistry Small molecule chemistry Recombinant product Recombinant product

Amgen + J&J + Kyowa Hakko Erythropoietin Kirin Otsuka + BMS Novartis Eisai + Pfizer 5-HT1A & D2 partial agonist & 5-HT2 receptor antagonist Tyrosine kinase inhibitor Acetylcholinesterase inhibitor

Boehringer Ingelheim + Pfizer Muscarinic antagonist Sanofi Amgen Merck + Ono + Almirall Eli Lilly + Shionogi Forest + Lundbeck + Others Teva + Sanofi Takeda + AstraZeneca + Almirall Boehringer + Astellas + Bayer Sanofi + BMS + Dainippon + Shionogi Pfizer + Eisai Amgen + Kyowa Hakko Kirin Novartis + Roche Gilead Sciences Sanofi AstraZeneca + Sigma-Tau Gilead + Torii Pfizer + Astellas Biogen Idec Novo Nordisk Daiichi Sankyo + Forest Celgene Pfizer Merck & Co Merck KGaA + Pfizer Eli Lilly Merck + Sigma-Tau Novo Nordisk Eli Lilly Heparin, low molecular weight (LMWH) Colony stimulating factor Dipeptidyl peptidase IV (DPPIV) inhibitor SNRI SSRI MS agent Angiotensin II antagonist Angiotensin II antagonist & thiazide Angiotensin II antagonist Alpha 2 delta ligand Erythropoietin Anti-VEGF MAb NNRTI & NRTI Taxane Beta 2 adrenoreceptor agonist & corticosteroid NRTI COX-2 inhibitor Interferon beta Insulin Angiotensin II antagonist Immunomodulator Pneumococcal vaccine Cholesterol absorption inhibitor Interferon beta Thymidylate synthase inhibitor Angiotensin II antagonist Insulin Insulin

Source: EvaluatePharma (25 MAY 2011) Note: Sales represent company reported sales where available, otherwise based on an average of equity analyst estimates.

Copyright 2011 EvaluatePharma Ltd. All rights reserved.

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2010: Top 50 Selling Products in the USA


Plavix Overtakes Lipitor to become USA No. 1 EvaluatePharma found that sales of Plavix (clopidogrel), co-promoted by BMS and Sanofi in the US, expanded 11% to $6.2bn, making it the biggest product in the US in 2010. Conversely the biggest product in 2009, Pfizer's cholesterol lowering treatment, Lipitor, fell 6% in the USA, with 2010 sales of $5.3bn. The patents on both Plavix and Lipitor are set to expire in November 2011.
USA Product Sales ($bn) Product 1 Plavix 2 Lipitor 3 Seretide/Advair 4 Seroquel 5 Epogen/Procrit 6 Actos 7 Abilify 8 Enbrel 9 Singulair 10 Remicade 11 Avastin 12 Rituxan 13 Humira 14 Lantus 15 Cymbalta 16 Nexium 17 Neulasta 18 Crestor 19 Diovan 20 Zyprexa 21 Lexapro 22 Copaxone 23 Januvia/Janumet 24 Lovenox/Clexane 25 Atripla 26 OxyContin 27 Aricept 28 Spiriva 29 Prevnar 13 30 Celebrex 31 Herceptin 32 Avonex 33 Revlimid 34 Lyrica 35 Lucentis 36 Levaquin 37 Truvada 38 Namenda 39 Gleevec/Glivec 40 Zetia 41 Effexor 42 Humalog 43 Aranesp 44 Vytorin 45 Provigil 46 Taxotere 47 Viagra 48 TriCor 49 Alimta 50 Premarin Generic Name clopidogrel bisulfate atorvastatin calcium fluticasone propionate; salmeterol xinafoate quetiapine fumarate epoetin alfa pioglitazone hydrochloride aripiprazole etanercept montelukast sodium infliximab bevacizumab rituximab adalimumab Company Bristol-Myers Squibb + Sanofi Pfizer GlaxoSmithKline AstraZeneca Amgen + J&J Takeda Otsuka + BMS Amgen + Pfizer Merck & Co Johnson & Johnson Roche Roche + Biogen Idec Abbott Laboratories Pharmacological Class Platelet ADP antagonist Statin/ HMG CoA reductase inhibitor Beta 2 adrenoreceptor agonist & corticosteroid 5-HT2 (serotonin) & dopamine D2 antagonist Erythropoietin PPAR gamma agonist 5-HT1A & D2 partial agonist & 5-HT2 receptor antagonist TNFa inhibitor Leukotriene D4 antagonist Anti-TNFa MAb Anti-VEGF MAb Anti-CD20 MAb Anti-TNFa MAb Insulin SNRI Proton pump inhibitor (PPI) Colony stimulating factor Statin/ HMG CoA reductase inhibitor Angiotensin II antagonist Atypical anti-psychotic SSRI MS agent Dipeptidyl peptidase IV (DPPIV) inhibitor Heparin, low molecular weight (LMWH) NNRTI & NRTI Opioid agonist Acetylcholinesterase inhibitor 2009 5,556 5,667 4,057 3,416 3,827 3,207 3,296 3,283 3,044 3,088 3,061 2,784 2,519 2,661 2,552 2,835 2,527 2,100 2,492 2,332 2,270 1,917 1,876 2,539 1,646 2,895 2,099 1,518 1,697 1,446 1,406 1,039 1,504 1,106 1,478 1,178 1,115 1,088 1,264 2,398 1,208 1,251 1,230 961 1,153 962 1,108 816 1,046 107,517 2010 6,154 5,329 4,026 3,747 3,594 3,582 3,348 3,304 3,219 3,099 3,068 2,910 2,872 2,832 2,772 2,695 2,654 2,640 2,520 2,496 2,300 2,287 2,139 1,910 1,909 1,800 1,795 1,766 1,761 1,580 1,530 1,492 1,433 1,424 1,402 1,312 1,309 1,300 1,285 1,227 1,226 1,222 1,103 1,077 1,060 1,043 992 984 957 949 110,434 % Growth +11% -6% -1% +10% -6% +12% +2% +1% +6% +0% +0% +5% +14% +6% +9% -5% +5% +26% +1% +7% +1% +19% +14% -25% +16% -38% -15% +16% n/m -7% +6% +6% +38% -5% +27% -11% +11% +17% +18% -3% -49% +1% -12% -12% +10% -10% +3% -11% +17% -9% +3% USA Age Company (Yrs) 13.5 14.4 10.8 13.7 22.0 11.9 8.5 12.6 13.3 12.8 7.2 13.5 8.4 11.1 6.8 10.3 9.3 7.8 14.4 14.7 8.8 14.4 4.6 18.2 4.9 15.5 14.5 7.3 1.2 12.4 12.7 15.0 5.4 6.4 4.9 14.4 6.8 7.6 10.0 8.6 17.4 15.0 9.7 6.8 12.4 15.0 13.2 9.7 7.3 69.1 12.1 Organic Organic Company acquisition Organic Company acquisition Company acquisition Company acquisition Company acquisition Company acquisition Organic Organic Joint venture In-licensed Organic Organic In-licensed In-licensed Company acquisition Company acquisition Joint venture Organic Organic Organic Company acquisition Company acquisition Company acquisition Organic Organic Company acquisition Company acquisition In-licensed Company acquisition In-licensed Organic Company acquisition Company acquisition Organic Joint venture Company acquisition Company acquisition Company acquisition Organic Company acquisition In-licensed Company acquisition Strategy In-licensed Company acquisition Organic Organic

insulin glargine recombinant Sanofi duloxetine hydrochloride esomeprazole magnesium pegfilgrastim rosuvastatin calcium valsartan olanzapine escitalopram oxalate glatiramer acetate sitagliptin phosphate enoxaparin sodium efavirenz; emtricitabine; tenofovir oxycodone hydrochloride donepezil hydrochloride tiotropium bromide monohydrate pneumococcal vaccine celecoxib trastuzumab interferon beta-1a lenalidomide pregabalin ranibizumab levofloxacin emtricitabine; tenofovir disoproxil fumarate memantine hydrochloride imatinib mesylate ezetimibe venlafaxine hydrochloride insulin lispro recombinant darbepoetin alfa ezetimibe; simvastatin modafinil docetaxel sildenafil citrate fenofibrate pemetrexed disodium estrogens, conjugated Eli Lilly AstraZeneca Amgen AstraZeneca Novartis Eli Lilly Forest Laboratories Teva Pharmaceutical Industries Merck & Co Sanofi Gilead Sciences Purdue Pharma Eisai

Boehringer Ingelheim + Pfizer Muscarinic antagonist Pfizer Pfizer Roche Biogen Idec Celgene Pfizer Roche Johnson & Johnson Gilead Sciences Forest Laboratories Novartis Merck & Co (SGP) Pfizer (Wyeth) Eli Lilly Amgen Merck & Co (SGP) Cephalon Sanofi Pfizer Abbott Laboratories Eli Lilly Pfizer (Wyeth) Pneumococcal vaccine COX-2 inhibitor Anti-HER2 (ErbB-2) MAb Interferon beta Immunomodulator Alpha 2 delta ligand Anti-VEGF MAb Quinolone NRTI NMDA antagonist Tyrosine kinase inhibitor Cholesterol absorption inhibitor SNRI Insulin Erythropoietin Statin/ HMG CoA reductase inhibitor & cholesterol absorption inhibitor Anti-narcoleptic Taxane Phosphodiesterase V (PDE5) inhibitor Fibrate Thymidylate synthase inhibitor Oestrogen agonist

Total

Source: EvaluatePharma (25 MAY 2011) Note: Sales represent company reported sales where available, otherwise based on an average of equity analyst estimates. EvaluatePharma endeavours to treat the sales from patent protected new formulations of existing products as distinct entities where possible. Epogen/ Neulasta/ Aranesp developed via Kirin-Amgen joint venture.

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