Orphan Drug Report 2013

April 2013

Welcome to the EvaluatePharma Orphan Drug Report 2013

The first edition of EvaluatePharmas Orphan Drug Report brings together many of our analyses to provide top-level insight, from the worlds financial markets, into the expected performance of the orphan drug market between now and 2018. Based on EvaluatePharmas coverage of over 4,000 of the worlds leading pharmaceutical and biotech companies, the Orphan Drug Report 2013 highlights trends in prescription sales for orphan vs. non-orphan drugs, orphan designation analysis in US and Europe, product and company performance, phase III R&D spend and return on investment. Additional copies are available at: www.evaluategroup.com/orphandrug2013. Since 1996 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 Evaluates range of services contact us:
North America:

Debbie Paul Tel: +1 617 573 9453 Email: debbie.paul@evaluategroup.com

Rest of the World :

Will Hau Tel: +44 (0)20 7377 0800 Email: will.hau@evaluategroup.com

Japan:

Hiroshi Yamazaki Tel: + 81 (0) 80 1164 4754 Email: hiroshi.yamazaki@evaluategroup.com

Copyright 2013 Evaluate Ltd. All rights reserved.

 For general questions:

Christine Lindgren Tel: +1 617 866 3906 Email: christine.lindgren@evaluategroup.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 Evaluate Ltd. While all reasonable steps have been taken to ensure that the data presented are accurate, Evaluate Ltd. cannot accept responsibility for errors or omissions. Neither does Evaluate Ltd. warrant the accuracy, merchantability or fitness of use for a particular purpose of the data.

EvaluatePharma Orphan Drug Overview

An orphan drug is a pharmaceutical product aimed at rare diseases or disorders. The development of orphan drugs has been financially incentivised through US law via the Orphan Drug Act of 1983. The National Organization for Rare Disorders (NORD), which was instrumental in establishing the 1983 Act, currently estimates 30 million Americans suffer from 7,000 rare diseases. Prior to the 1983 Act, 38 orphan drugs were approved. To date, 425 indication designations covering 347 drugs have been approved. The success of the original Orphan Drug Act in the US led to it being adopted in other key markets, most notably in Japan in 1993 and the European Union in 2000. Rare Disease Patient Populations are Defined in Law as: USA: <200,000 patients (<6.37 in 10,000, based on US population of 314m) EU: <5 in 10,000 (<250,000 patients, based on EU population of 506m) Japan: <50,000 patients (<4 in 10,000 based on Japan population of 128m)

The success of the original Orphan Drug Act in the US led to it being adopted in other key markets, most notably in Japan in 1993 and the European Union in 2000.
Financial Incentives by Law Include:
Market Exclusivity

 USA: 7 Years of marketing exclusivity from approval; Note: Majority of orphan drugs have a compound patent beyond 7 years. The market exclusivity blocks same drug recombinant products. E.g. Fabrazyme (Genzyme, now Sanofi) vs. Replagal (Transkaryotic, now Shire). Same drug exclusion can be overturned if clinically superior (mix of efficacy/ side effects). E.g. Rebif overturned Avonexs orphan drug exclusivity (7 MAR 2002) EU: 10 Years of marketing exclusivity from approval
Reduced R&D Costs

USA: 50% Tax Credit on R&D Cost USA: R&D Grants for Phase I to Phase III Clinical Trials ($30m for each of fiscal years 2008-12) USA: User fees waived [FFDCA Section 526: Company WW Revenues <$50m] Methodology on Classifying an Orphan Drug
Copyright 2013 Evaluate Ltd. All rights reserved.

EvaluatePharma has identified all products that have orphan drug designations filed in the US, EU or Japan. These will be made available as part of the core EvaluatePharma service. To further enhance analysis EvaluatePharma has defined a clean Orphan sub-set of products which excludes products where less than 25% of lifetime sales are expected to come from orphan indications. This has led to the exclusion of products, such as Avastin, Enbrel, Herceptin, Humira and Remicade, all of which have orphan designations for indications contributing less than 25% to lifetime sales. All sales analysis in the report is based on this clean Orphan sub-set of products.

EvaluatePharma Foreword
he first edition of the Orphan Drug Report is in response to requests from our clients for an in-depth, fact-based analysis of the orphan drug market. To facilitate the analysis, EvaluatePharma has enhanced its core product database to include new orphan drug data fields and has integrated US, EU and Japan orphan drug designation databases. Growth in Orphan Drugs Set to be Double that of Overall Prescription Drug Market In this report we find that the worldwide orphan drug market is set to grow to $127bn (see page 6), a compound annual growth rate of +7.4% per year between 2012 and 2018. This predicted growth rate is double that of the overall prescription drug market, excluding generics, which is set to grow at +3.7% per year. Orphan drugs are set to contribute 15.9% to the overall prescription drug market in 2018, excluding generics, up from 5.1% in 1998. Uplift in US Designations from 2003 EvaluatePharma finds that there was a notable uplift in the number of US orphan designations from 2003 (see page 12) to 2010. The uplift in designations, and therefore R&D investment in this area, is due to superior R&D productivity in the orphan drug sector. The success of a second wave of pioneers in orphan drug development, such as Amgen, Biogen Idec, Genentech (Roche), Genzyme and Schering-Plough proved that significant returns could be made in smaller patient populations, through higher prices from innovative new drugs. High R&D costs in developing primary care products, coupled with high profile clinical & regulatory failures and the continuing genericization of primary care markets has further drawn Big Pharma into the orphan sector. Orphan Drugs Offer Superior Returns on Investment vs. Non-Orphans This report confirms the hypothesis that orphan drugs currently offer a greater return on investment (RoI) than non-orphans. The current stock of Phase III/ Filed orphan products is expected to yield a return on investment of x10.3 vs. x6.0 for non-orphans (see page 10). This significantly better RoI is primarily due to the fact that orphan drugs require a median phase III trial size of 528 patients vs. 2,234 for nonorphans (see page 9). We estimate the average phase III cost at $85m vs. $186m for the key phase III trial. When factoring in the potential 50% US tax credit, this can reduce the orphan cost to $43m vs. $186m for a non-orphan. Interestingly, we do not find orphan drug development time to be any quicker, with a median of 2.75 years (see page 9) between the start of phase III trials to filing with the FDA. Orphan Sector Cooling Down?; Designations Decline in 2012 The number of new orphan drug designations declined in 2012 to 188, from a peak of 203 in 2011 (page 12). This could signal a slowdown in investment in the sector. Need for a Common Drug Act?
Copyright 2013 Evaluate Ltd. All rights reserved.

An interesting paradox of the success of the original 1983 Orphan Drug legislation is that it was assumed that common diseases were economically incentivised enough. Is this still the case? There is certainly the need for mass market drugs to combat problems such as drug-resistant infections, but with the development of drugs for large disease populations now costing potentially billions of dollars, will Big Pharma take on the risk? We may well require a Common Disease Drug Act before long, to redress the imbalance.

Anthony Raeside Head of Research

3

EvaluatePharma Orphan Drug Report 2013 Analysis Highlights

Worldwide Orphan Drug Sales Forecast to Total $127bn (CAGR 2012 to 2018: +7.4% ); Double Overall Prescription Market Growth  Orphan Drugs Set to be 15.9% of Worldwide Prescription Sales by 2018 (excluding generics)  Novartis Set to Maintain Number One Position in Orphan Drug Sales to 2018  Bristol-Myers Squibb, GSK and Sanofi Set to March up the Orphan Sales Ranking Table  Rituxan (rituximab) No.1 Orphan Drug in 2018  Phase III Orphan Drug Development Cost Half that of Non-Orphan; Potentially a Quarter with US Tax Breaks  Phase III Drug Development Time for Orphan is No Quicker than Non-Orphan  Orphan Drug FDA Approval Time 9 months vs. 10 months for Non-Orphan  Expected Return on Investment of Phase III/ Filed Orphan Drugs 1.7 Times Greater than Non-Orphan Drugs  Elotuzumab (AbbVie/ BMS) is Most Valuable Pure R&D Orphan Drug  FDA Orphan Designations Decline 7% in 2012; European Designations up 44%; Japan Designations up 33%  FDA Approves 15 New Orphan Drugs in 2012 vs. 14 in 2011; Orphans 35% of Total FDA New Drug Approvals in 2012  Kyprolis Most Promising New Orphan Drug Approved by FDA in 2012  18.5% of EU Orphan Designations for Ultra Rare Diseases  Acute Myeloid Leukaemia is Indication with Most Filed Orphan Drug Designations in EU

Copyright 2013 Evaluate Ltd. All rights reserved.

Orphan Drugs Set to be of Worldwide Prescription Sales by 2018 (excluding generics)

15.9%

Table of Contents

6 7 8 9

Worldwide Orphan Drug Sales (1998-18) Worldwide Orphan Drug Sales in 2018: Top 20 Companies 2018: Top 30 Selling Orphan Drugs in the World Phase III Trial Size & Approval Time: Orphan vs. Non-Orphan

10 R&D Costs (PIII/ Filed) & Expected Investment Returns (NPV) 11 2018: Top 20 Orphan R&D Products based on NPV

12 USA, EU & Japan Orphan Designations per Year & Cumulative (1983-12) 13 FDA Approvals of Designations & New Drugs (NMEs/ BLAs): 1999 to 2012 14 FDA New Drug Approval Analysis (NMEs/ BLAs) 2012: Orphan vs. Non-Orphan 15 EU Orphan Designations: Historic Distribution by Prevalence 16 EU Orphan Designations: Top 20 Indications 17 About EvaluatePharma

Copyright 2013 Evaluate Ltd. All rights reserved.

Worldwide Orphan Drug Sales (1998-18)

Worldwide Orphan Drug Sales (1998-18)
Worldwide Orphan Drug Sales Forecast to Total $127bn (CAGR 2012 to 2018: +7.4% ); Double Overall Rx Market Growth Orphan Drugs Set to be 15.9% of Worldwide Prescription Sales by 2018 (excluding generics) EvaluatePharma finds that the market for orphan drugs, based on the consensus forecast for the leading 500 pharmaceutical and biotechnology companies, will grow by 7.4% per year (CAGR) between 2012 and 2018 to $127bn. The growth of the orphan drug market is almost double that of the overall prescription drug market, which is set to grow by 3.7% over the period 2012-2018. Orphan drugs are set to account for 15.9% of global prescription sales in 2018, excluding generics, up from 5.1% in 1998. In 2012 orphan drug sales increased 7.1% to $83bn vs. 2011, in contrast to overall prescription drug sales (excluding generics) which declined 2.1% to $645bn. Worldwide Orphan Drug Sales & Share of Prescription Drug Market (1998-18) Source: EvaluatePharma (23 APR 2013)
140 120 100 80 60 40 20 0 5.1%
+7.4% CAGR 2012-18

WW Prescription Sales ($bn)

WW Orphan Sales WW Orphan as % of WW RX

15.9%

18% 16% 14% 12% 10% 8% 6% 4% 2% 0%

WW Orphan Sales as a % of WW Rx Sales (excl. Generics)

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

2017 2015
+8.1% 605 709 104

Worldwide Orphan & Prescription Drug Sales (2004-18)

WW Prescription Sales ($bn) Year 2004 2005 2006 2007
28 33 38 46

WW Orphan Drug Sales Growth per Year Orphan Sales as a % of Rx

2008
56

2009
+9.0% 550 610 61

2010
69

2011
78

2012
+7.1% 562 645 83

2013
+7.9% 564 653 90

2014
+7.7% 581 677 96

2018

2016
+5.8% 631 741 110

2017
+6.9% 654 772 118

2018
+8.0% 675 803 127

6.6% 399 427

+15.7% +15.8% +21.9% +20.4% 7.1% 429 462 7.6% 463 501 8.4% 506 552 9.4% 540 596

10.0%

+13.0% +12.8% 11.0% 556 625 11.8% 582 659

12.9% -3.3% -2.1%

13.7%

14.2%

14.7%

14.9%

15.3%

15.9%

WW Non-Orphan Drug Sales Growth per Year WW Prescription (Rx) (less Generics) Growth per Year

+7.6% +8.1%

+7.8% +8.4%

+9.3% +10.2%

+6.7% +7.9%

+1.8% +2.5%

+1.2% +2.3%

+4.6% +5.5%

+0.3% +1.3%

+3.0% +3.7%

+4.1% +4.7%

+4.3% +4.5%

+3.7% +4.2%

+3.2% +3.9%

Copyright 2013 Evaluate Ltd. All rights reserved.

Note: Industry sales based on Top 500 pharmaceutical and biotech companies. Sales to 2012 based on company reported sales data. Sales forecasts to 2018 based on a consensus of leading equity analysts' estimates for company product sales and segmental sales. All sales analysis based on EvaluatePharma's clean Orphan sub-set of products, which excludes products where less than 25% of lifetime sales come from orphan indications.

Source: EvaluatePharma (23 APR 2013)

WW Orphan Drug Market CAGR 12-18 +7.4% WW Non-Orphan Drug Market CAGR 12-18 +3.1% WW Prescription (Rx) excluding Generics CAGR 12-18 +3.7%

Worldwide Orphan Drug Sales in 2018: Top 20 Companies

Worldwide Orphan Drug Sales in 2018: Top 20 Companies
Novartis Set to Maintain Number One Position in Orphan Drug Sales to 2018 Bristol-Myers Squibb, GSK and Sanofi Set to March up the Orphan Sales Ranking Table EvaluatePharma finds that Novartis will maintain its position as the world's number one orphan drug company in 2018 with sales of $11.8bn. Novartis has a strong orphan portfolio built around Gleevec and Tasigna for chronic myelogenous leukaemia and gastrointestinal stromal tumors. Celgene is set to climb 2 places to rank third with $8.6bn in sales in 2018. Within Global Majors Sanofi, up 4 places to 5th, Bristol-Myers Squibb, up 9 places to 7th, and GlaxoSmithKline, up 12 to 8th, show the increased focus on the orphan sector. WW Orphan Prescription Drug Sales in 2018: Top 10 Companies Source: EvaluatePharma (23 APR 2013)
WW Orphan Prescription Sales ($bn) 14 12 10 8 6 4 2
Sales ($bn) CAGR 2012-18 (%) Ranking Chg. 2012-18

11.8 9.4 8.6 7.2 5.5 5.2 4.7 4.1

3.7

3.2

Alexion Pharmaceuticals

Bristol-Myers Squibb

GlaxoSmithKline

Celgene

Novartis

Roche

Bayer

Worldwide Orphan Drug Sales (2012/18): Top 20 Companies & Total Market
Company Novartis Roche Celgene Pfizer Sanofi Bayer Bristol-Myers Squibb GlaxoSmithKline Alexion Pharmaceuticals Baxter International Eli Lilly Biogen Idec Shire Merck KGaA Johnson & Johnson Novo Nordisk Vertex Pharmaceuticals Amgen Actelion Merck & Co Total Top 20 Other Total 2012
10.9 9.0 4.9 5.4 2.9 4.2 1.7 1.4 1.1 2.5 2.6 2.9 1.7 3.0 1.8 1.5 0.2 2.6 1.8 64.0 19.0 83.0 1.8

Copyright 2013 Evaluate Ltd. All rights reserved.

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

WW Orphan Sales ($bn) 2018 % CAGR 12-18

11.8 9.4 8.6 7.2 5.5 5.2 4.7 4.1 3.7 3.2 3.0 2.9 2.8 2.6 2.6 2.4 2.2 2.0 1.8 87.3 127.4 40.1 1.6 +1% +1% +5% +3%

13.1% 6.0% 3.5% 2.1% 1.6% 3.0% 3.1% 3.5% 3.6% 2.0% 2.1% 1.9% 3.1% 2.2% 2.2% 0.2% 1.4%

2012

WW Market Share 2018 Chg. (+/-)

9.3% 7.4% 6.8% 4.3% 3.7% 3.3% 2.5% 2.3% 2.3% 2.0% 2.2% 2.0% 1.9% 1.6% 1.4% 68.5% 1.3% 1.7% 2.9% -3.8% -3.4% -0.9% -1.0%

+10% +11% +18% +20% +22% +4% +2% +0% +9% +7% +53% -4% -0% +5.3% +7.4% -2% +8% -2%

10.8% 6.6% 5.1%

5.6% 4.1%

+0.8% +0.8% +1.6% +1.6% +1.5% -0.6% -0.8% +0.2% -1.6% -0.1% -1.2%

+0.0% -1.5% -0.8% -8.6% -0.9%

+1.5%

+13.2%

77.1%

Source: EvaluatePharma (23 APR 2013)

100.0%

22.9%

100.0%

31.5%

Note: All sales analysis based on EvaluatePharma's clean Orphan sub-set of products, which excludes products where less than 25% of lifetime sales come from orphan indications.
7

Baxter International Rank Chg. (+/-)

+2 +4 +9 -1 +12 +12 +2 -1 -4 -7 +4 +28 -7 -5 -7 +2

Pfizer

Sanofi

2018: Top 30 Selling Orphan Drugs in the World

Rituxan (rituximab) No.1 Orphan Drug in 2018 EvaluatePharma finds that Rituxan is the world's largest orphan drug in 2018, with sales of $6.9bn for all indications. Rituxan from Roche was first approved in November 1997 for the orphan treatment of non-Hodgkin B-cell lymphoma. Rituxan is also approved for the orphan disease chronic lymphocytic leukaemia and has non-orphan approval for rheumatoid arthritis. Celgene's Revlimid for multiple myeloma & myelodysplastic syndromes is set to be a close second with $6.6bn in worldwide sales. Top 30 Orphan Drugs in 2018 Source: EvaluatePharma (23 APR 2013)
WW Product Sales in 2018 ($m) 7,000 6,000 5,000 4,000 3,000 2,000 1,000

2018: Top 30 Selling Orphan Drugs in the World

6,948

6,598

3,404

2,919

2,584

2,381

2,085

2,017

2,005

1,917

Velcade

Tasigna

Avonex

Yervoy

Rituxan

Revlimid

Worldwide Top 30 Selling Orphan Drugs in 2018

WW Product Sales ($m) Rank Product Rituxan 1 Soliris Generic Name lenalidomide everolimus eculizumab rituximab Company Celgene R o ch e Marketed Phase (Current) Anti-CD20 MAb Pharmacological Class 2012 2018 7,155 6,948 CAGR +10% -0%

Revlimid

14 16

13

12

11

10

Yervoy Rebif

Alimta

Avonex

Velcade

Tasigna

Afinitor

pemetrexed disodium dasatinib ipilimumab

interferon beta-1a

bortezomib

nilotinib hydrochloride

Eli Lilly

Biogen Idec

J&J/ Takeda

Novartis

Novartis

Alexion Pharmaceuticals

Marketed

Marketed

Marketed

Marketed

Anti-complement factor C5 MAb Signal transduction inhibitor Interferon beta Proteasome inhibitor

Immunomodulator

Rapamycin analogue (mTOR inhibitor)

1,134 998 797

3,767

Marketed Marketed Marketed

Marketed

Sprycel

Bristol-Myers Squibb Merck KGaA / Pfizer Incyte/ Novartis Pfizer

Thymidylate synthase inhibitor Anti-CTLA4 MAb Interferon beta Tyrosine kinase inhibitor

2,594 706

2,913

2,358

2,017

2,085

2,381

2,584

2,919

3,404

6,598

+17% +0% -4% -5%

+24%

+20%

15

Sutent

Jakavi

Kalydeco

19

18

17

24

23

22

21

20

Copaxone Advate Ibrutinib

Nexavar

NovoSeven

Kogenate

Kyprolis

eptacog alfa

octocog alfa

carfilzomib

sunitinib malate

ruxolitinib phosphate

ivacaftor

interferon beta-1a

Bristol-Myers Squibb

Vertex Pharmaceuticals

Marketed Marketed Marketed

Marketed

Marketed

Marketed

1,019 172

CFTR potentiator

2,433 150 64

Janus kinase (JAK)-1/2 inhibitor Proteasome inhibitor Factor VII Factor VIII Multiple tyrosine kinase inhibitor

glatiramer acetate factor VIII (procoagulant) ibrutinib

sorafenib tosylate

Teva/ Sanofi

Bayer/ Onyx

Novo Nordisk

Bayer

Onyx Pharmaceuticals

1,236 1,520

1,559 1,521 1,499 1,516

1,702

1,766

1,917

2,005

+11% +47% +4% -0% -5%

+19%

1,555

+48% +70% -0%

Gleevec

Myozyme

Cerezyme

alglucosidase alfa imatinib mesylate octreotide acetate deferasirox macitentan crizotinib

imiglucerase

Baxter International Sanofi Sanofi

Pharmacyclics

Marketed Phase III

Marketed

Marketed

Marketed

MS agent

Multi-kinase inhibitor Bruton's tyrosine kinase (Btk) inhibitor Glucocerebrosidase Factor VIII

1,018 -

1,543

4,027 2,234 594 814

1,463

1,295 1,229 1,283

-17% -9% n/a

+6%

Marketed Marketed Marketed

Novartis Novartis Actelion Pfizer Novartis

Marketed Marketed Filed Marketed

Tyrosine kinase inhibitor Growth hormone & IGF-1 inhibitor Endothelin receptor antagonist ALK & c-Met kinase inhibitor CNS depressant Immunomodulator Iron chelator

Alpha glucosidase

4,675 1,512 870 112 -

1,025 989 978 969 936

1,128

1,211

+11% -22% -7% +2% +42% n/a n/a

+7%

Copyright 2013 Evaluate Ltd. All rights reserved.

25 27 26

Sandostatin LAR Opsumit Xyrem Other Exjade

28

29

Xalkori

30

Pomalyst

sodium oxybate pomalidomide

Jazz Pharmaceuticals Celgene

Marketed

Marketed

Approved

379

Source: EvaluatePharma (23 APR 2013)

Total

36,238

83,033

127,399

69,071

922

925

+16%

+11% +7%

Note: Sales represent company reported sales where available, otherwise based on an average of equity analyst estimates. Worldwide sales represent sales for all indications. All sales analysis based on EvaluatePharma's clean Orphan sub-set of products, which excludes products where less than 25% of lifetime sales come from orphan indications.

Sprycel

Afinitor

Alimta

Soliris

Phase III Trial Size & Approval Time: Orphan vs. Non-Orphan
Phase III Trial Size & Approval Time: Orphan vs. Non-Orphan
Phase III Orphan Drug Development Cost Half that of Non-Orphan; Potentially a Quarter with US Tax Breaks Phase III Drug Development Time for Orphan is No Quicker than Non-Orphan Orphan Drug FDA Approval Time 9 months vs. 10 months for Non-Orphan EvaluatePharma estimates that the average phase III clinical trial cost for an orphan drug is roughly half that of non-orphan drugs at $85m, vs. $186m for a non-orphan. In addition, with 50% US tax credit, available via the Orphan Drug Act, the potential cost could be a quarter of non-orphan at $43m vs. $186m for non-orphans. Orphan drugs required a median 528 patients for phase III trials, versus a median 2,234 patients for non-orphan drugs. The average phase III trial sizes came in at 633 patients for orphan drugs versus 3,758 for non-orphans. EvaluatePharma found that there was no statistically significant difference in phase III trial length, at a median of 2.75 years. Median FDA approval times were 9 months for orphan vs. 10 months for non-orphans, due to orphans tending to receive Priority Review. Phase III Trials Sizes: Orphan vs. Non-Orphan Source: EvaluatePharma (23 APR 2013)
0 Orphan 500 1,000 1,500

Median Phase III Size 2,000 2,500

528

Non-Orphan

2,234

1,094

EU Prescription Drug Sales (2009/11): Top 20 Companies Average Phase III Trials Sizes (All New Drug Products Entering Phase III from 1 JAN 2000)
Phase III Trial Size No. of Total Average Products (n=) Patients
3,758 2,838 633 585 829 244 2,198,234 2,352,680 154,446

ALL

Orphan / Non-Orphan = 23.6% 16.8% 41.7% Source: EvaluatePharma Success Rates (23 APR 2013) Phase III Trials Length (yrs): Orphan vs. Non-Orphan
0 1 2

Product Type Orphan Non-Orphan ALL

Median
2,234 1,094 528

% of
93% 7%

Phase III Cost ($m) Estimated * Median Average Total

151 96 186 85

100%

63.5%

125

45.9%

156

108,658

20,793

Potential 50% US Tax Credit Median Average

151 48 186 43

19.1%

129,451

31.8%

22.9%

Median Length (yrs) 3

FDA Approval Time: Orphan vs. Non-Orphan

0 5

Median (mths)

10

Orphan

2.75

Orphan

9.0

Non-Orphan

2.72

Non-Orphan

10.1

Copyright 2013 Evaluate Ltd. All rights reserved.

2.74

10.0

ALL

Average Phase III & FDA Approval Times

Phase III Length (yrs) No. of Average Products (n=)
2.83 2.92 2.86 204 97

ALL

Orphan / Non-Orphan

Product Type Orphan Non-Orphan ALL

Median
2.72 2.75 2.74

FDA Filed to Approved (mths) No. of Median Average Products (n=)

10.08 9.99 9.04 13.07 9.65 170 82

+0.9%

+2.9%

301

-10.3% -26.2%

11.96

252

Source: Provisional Data from EvaluatePharma's Forthcoming Success Rates & Clinical Trial Timelines (23 APR 2013)

R&D Costs (PIII/ Filed) & Expected Investment Returns (NPV)

R&D Costs (PIII/ Filed) & Expected Investment Returns (NPV)
Expected Return on Investment of Phase III/ Filed Orphan Drugs 1.7 Times Greater than Non-Orphan Drugs Phase III/ Filed Orphan Drugs are 20% of Industry Phase III R&D Spend, but 32% of the Value Creation in the Industry EvaluatePharma finds that the current value, based on NPV, of pipeline phase III/ filed orphan drugs is $57bn versus $131bn for non orphans. When looking at the Industry's expected phase III costs to bring all products to market, orphan drugs cost $5.5bn versus $21.8bn for non orphans. We have not assumed any US tax credits in the calculation. The main difference in cost is driven by the differing phase III trial sizes, with all current phase III/ filed orphans set to require a total of 32,500 patients for phase III trials, versus 621,600 patients for non-orphans. The current expected return on investment can be calculated taking the NPV divided by the phase III cost. The Industry's expected return on orphan drugs is 10.3 times the investment (phase III), versus 6.0 times the investment on non-orphans. R&D (Phase III/ Filed): NPV ($bn) Phase III Cost ($bn)

140 120 100 Cost ($bn) NPV ($bn) 80 60 40 20 0

Orphan Non-Orphan
57 131

25 20 15 10 5 0
5.5 Orphan Non-Orphan 21.8

R&D NPV for Phase III/ Filed ($bn) Value Creation

Phase III R&D Costs ($bn) Cost of Phase III 20%

30%
Orphan Non-Orphan Orphan Non-Orphan

70%

80%

Value Creation (NPV) for NMEs Phase III/ Filed with NPV
Avg. Product NPV ($m) 723 622 No. of Products (n=) 181 91

Phase III Clinical Trial Cost (estimated) Available Current Phase III Costs
Phase III Cost ($bn) 21.8 5.5 No. of Products (n=) 122 60

Expected Return NPV minus Phase III Cost

Net Return NPV - Phase III Cost +109.0 +51.2 NPV/ Phase III Cost 10.3 6.9 6.0

Type Non-Orphan Orphan

NPV ($bn) 131 57

As a % 70% 30%

No. of Patients 621,641 +5.2% +5.0% 32,518

As a % 80% 20%

Total

Orphan/ Non-Orphan Orphan/ Total

+43.3% +30.2%

187

100%

+86.1% +90.3%

689

+50.3% +33.5%

272

654,159

+25.1% +20.1%

27.3

100%

+49.2% +33.0%

182

+47.0% +32.0%

+160.1

Copyright 2013 Evaluate Ltd. All rights reserved.

Investment Return Relative to Non-Orphan 1.72 Source: Provisional Data from EvaluatePharma's Forthcoming Success Rates & Clinical Trial Timelines (23 APR 2013)
Note: The sample size for product NPVs (n=272) is greater than the estimates of phase III trial sizes (n=182). This is due to NPVs being split by licensing deals. Not all products have an estimate of Phase III trial costs, mainly due to the fact certain products entered Phase III prior to 1 JAN 2000 (the current starting date of EvaluatePharma's Success Rate Model). Phase III trial costs have been estimated based on an algorithm using cost per patient per year.

10

2018: Top 20 Orphan R&D Products Based On NPV

Lilly's IMC-1121B World's Most Valuable R&D Orphan Drug* Elotuzumab (AbbVie/ BMS) is Most Valuable Pure Orphan Drug EvaluatePharma finds that Lilly's anti-VEGFr MAb IMC-1121B* in development for gastric and liver cancer (orphan), and a range of nonorphan cancers, is the world's most promising R&D orphan drug, with an NPV of $3.5bn. Elotuzumab (AbbVie/ BMS) for multiple myeloma, is the most valuable R&D product (NPV: $1.5bn) expected to derive all its sales from orphan indications. Top 30 Orphan Drugs in 2018 (Phase III/ Filed) Source: EvaluatePharma (23 APR 2013)
4,000 3,500 Product NPV ($m) 3,000 2,500 2,000 1,500 1,000 500 RG3638 Opsumit IMC-1121B Riociguat N9-GP GSK2118436 Ibrutinib BAY 86-6150
Company acquisition Company acquisition In-licensed Organic Organic Product acquisition Organic Organic In-licensed Product acquisition In-licensed Company acquisition Company acquisition Organic 34 722 324 667 1,161 70 9 11 8 8 Organic Organic Organic Organic Company acquisition Organic 32,518 621,641 10.3 6.0

2018: Top 20 Orphan R&D Products based on NPV

3,529

3,456

3,427 2,546 1,964 1,766 1,743 1,675

1,507

1,323

Worldwide Top 20 Orphan R&D Products based on NPV (Sales, NPV, PIII Cost & Expected Return)
Sales ($m) 2018 813 660 1,283 969 749 487 549 397 418 301 432 526 527 205 234 447 483 274 547 231 18,279 7,745 Rank Product 1 IMC-1121B 2 RG3638 3 Ibrutinib 4 Opsumit 5 Riociguat 6 N9-GP 7 GSK2118436 8 BAX 111 9 Elotuzumab 10 BAY 86-6150 11 Trametinib 12 rFVIIIFc 13 VX-809 14 Defibrotide 15 BAX 817 16 HyperAcute Pancreas Company Eli Lilly Roche Pharmacyclics Actelion Bayer Novo Nordisk Baxter International Bristol-Myers Squibb Bayer GlaxoSmithKline Biogen Idec Vertex Pharmaceuticals Gentium GlaxoSmithKline Phase (Current) Phase III Phase III Phase III Filed Filed Phase III Filed Phase III Phase III Phase III Filed Filed Phase III Filed Phase III Pharma Class Anti-VEGFr MAb Anti-mesenchymal epithelial transition (cMet) MAb NPV 3,529 3,456 3,427 2,546 1,964 1,766 1,743 1,675 1,507 1,323 1,285 1,271 1,188 1,125 983 951 939 850 843 816 23,456 56,642 WW Cost $m) 110 135 96 124 129 64 119 15 134 27 128 108 96 n/a 14 109 89 101 112 n/a 5,483 21,831 R&D PIII

Trial Size 1,144 490 350 1,292 1,339 156 1,234 36 1,390 65 1,331 394 1,002

Phase III

Return NPV/ PIII Cost Strategy 32 26 36 20 15 27 15 113 11 49 10 12 12

Bruton's tyrosine kinase (Btk) inhibitor Endothelin receptor antagonist Guanylate cyclase activator Factor IX B-Raf kinase inhibitor Von Willebrand factor Anti-CD37 MAb Factor VIIa MEK inhibitor Factor VIII Cystic fibrosis transmembrane conductance regulator (CFTR) corrector Cathepsin G inhibitor Factor VIIa Cancer vaccine N-acetyl-galactosidase6-sulfatase Factor VIII Angiotensin II antagonist Farnesoid X receptor (FXR) agonist

Baxter International

NewLink Genetics Phase III BioMarin Pharmaceutical Novo Nordisk Novartis Intercept Pharmaceuticals Filed Filed Filed Phase III

Copyright 2013 Evaluate Ltd. All rights reserved.

17 Vimizim 18 Turoctocog alfa 19 RLX030 20 Obeticholic acid Other

Total

vs. Non-Orphan:

40,425

130,793

Source: EvaluatePharma (23 APR 2013) Note: Sales represent company reported sales where available, otherwise based on an average of equity analyst estimates. Phase III trial costs represent an assumption on current phase III trial size for lead indication(s), derived from the enrolment size listed on clinicaltrials.gov via Evaluate Clinical Trials. *IMC-1121B: Majority of sales expected to be from non-orphan indications, but in Phase III for gastric and liver cancer (orphan). Factor VIII products for haemophilia A & B classified as orphan drugs.

Elotuzumab

BAX 111

11

USA, EU & Japan Orphan Designations per Year & Cumulative (1983-12)
USA, EU & Japan Orphan Designations per Year & Cumulative (1983-12)
FDA Orphan Designations Decline 7% in 2012; European Designations up 44%; Japan Designations up 33% EvaluatePharma found that the number of US orphan drug designations declined 7% in 2012 to 188. This is the first decline since 2007. European orphan designations expanded 44% to 147, reversing the decline seen in 2011. US orphan designations accepted noticeably accelerated from 64 in 2002 to a peak of around 203 in 2011. Orphan designations in Japan continued to surge ahead, up 33% to 32 designations. USA, EU & Japan Designation per Year (1983-2012) Source: EvaluatePharma (23 APR 2013)
200 Designations Per Year

USA Designations per Yr EU Designations per Yr Japan Designations per Yr

150

100

Strong increase from 2003

50

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

US, EU & Japan Orphan Designations per Year (1999-12 )

Year Orphan Designations 1999 2000 2001
94 78 83% 0 -6% -10% 80% 8 70 88 +47% +11% 60% 31 7 78 129

USA OD Applications Growth per Year USA Designations Accepted Growth per Year % Accepted EU Designations per Yr Growth per Year Japan Designations per Yr

2002
-11% -18% 56% 31 5 64 115

2003
+45% +48% 57% 36 7 95 167

2004
+4% +38% 75% 56 8 131 174

2005
+0% -6% 69 5 123 174

2006
+10% +15% 74% -9% +180% 14 63 142 191

2007
-5% 181

2008
+2% +41% 89% 66 165 185

2009
+35% +0% 91 7 165 250

2010
+29% +18% 60% 119 10 194 323

2011
-5% 306

2012 2012
-14% -7% 188 264 71% +44% +33% 32 147

71% +23% -38%

-18% 65% 79

117

66%

66% 102 24

+5%

203

20

Source: EvaluatePharma (23 APR 2013); USA OD applications per year from PAREXEL Consultin g USA, EU & Japan Designations Cumulative Total Source: EvaluatePharma (23 APR 2013)

-40%

12

+288% -42%

+0% -29%

+16% +40%

+56% +14%

+25% -29% 10

-16% +60% 16

+38% -56%

+31% +43%

-14% +140%

3000 2500 Total Designations 2000 1500 1000 500

Copyright 2013 Evaluate Ltd. All rights reserved.

USA Designations Total EU Designations Total Japan Designations Total

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

Cumulative US, EU & Japan Orphan Designations & US Approvals per Year (1999-12)
Year Orphan Designations Cumulative Total 1999 2000 2001 2002 2003 2004
994 1,064 +7% 8 1,142 +7% 39 1,206 +6% 70 1,301 +8% 106 +10% +53% +5% 175 162

USA Designations Total Growth per Year EU Designations Total Growth per Year Japan Designations Total Growth per Year

1,432

1,555 +9% 231

2005

1,697 +9% 294

2006

1,814 +7% 373

2007

1,979 +9% 439

2008

2,144 +8% 530

2009

2,338 +9% 649

2010

2,541 +9% 751

2011

2012
2,729 +7% 898

2012

136

Source: EvaluatePharma (23 APR 2013)

+9%

148

+388% +5% 155

+79% +3% 160

+51% +4% 167

+43% +3% 180

+27% +8% 194

+27% +5% 204

+18% +8% 220

+21% +3% 227

+22% +4% 237

+16% +10% 261

+20% +12% 293

12

FDA Approvals of Designations & New Drugs (NMEs/ BLAs): 1999 to 2012
FDA Approvals of Designations & New Drugs (NMEs/ BLAs): 1999 to 2012
FDA Approves 15 New Orphan Drugs in 2012 vs. 14 in 2011; Orphans 35% of Total FDA New Drug Approvals in 2012 FDA Approves 26 Designations in 2012, No Change on 2011 EvaluatePharma finds that 15 new orphan drugs (NMEs/ BLAs and biologicals) were approved in 2012 out of 43 new drugs. Orphan drugs represented 35% of the Industry's new drug output in 2012. Overall the FDA approved 26 designations, flat vs. 2011. This includes new indication approvals of already marketed products. USA & EUDrug Designation per Year & Cumaltive Total FDA Orphan Marketing Approvals & Orphan Drugs New Drugs (NMEs/ BLAs) Source: EvaluatePharma APR 2013) Source: EvaluatePharma (23 APR (20 2013)
No. of FDA Approved OD Designations No. of Orphan Drugs (NMEs/ BLAs)

30 25 20 15 10 5 0

Total FDA Approvals

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011 2010
-30% -60% 3 3 0 6 14

FDA Approved Orphan Designations & Drugs

1999 Year 20 No. of FDA Approved OD Designations % Chg. No. of Orphan Drugs (NMEs/ BLAs) % Chg. NME - Orphans BLA - Orphans Biologicals - Orphans 2000
-35% 13

2001
-54% 6

2002
+133% 14

2003
-14% 12

2004
+8% 13

2005
+46% 10 6 1 3 19

2006
+26% -20% 5 2 1 8 24

2007
-33% +0% 5 1 2 8 16

2008
-13% +13% 2 2 5 9 14

2009
+43% +67% 5 4 6 15 20

2011
+86% +133% 7 4 3 14 26

2012 2012
+0% +7% 11 3 1 15 26

Total FDA Approval Count (Orphan & Non-Orphan)

Year No. of NMEs Approved No. of Biologicals Approved Total NMEs + Biologicals % Chg. No. of Orphan Drugs (NMEs/ BLAs) as a % of Total 1999
35 40 5

2000
27 33 6

2001
24 32 8

2002
17 26 9

2003
21 35 14

2004
31 38 7

2005
18 28 10

2006
18 29 8 11

2007
16 26 8 10

2008
21 31 9 10

2009
19 34 15

2010
15 26 6 11

2011
24 35 11

2012
33 43 10

-18%

-3%

-19%

+35%

+9%

-26% 36% 10

+4% 28%

-10% 31%

+19% 29%

+10% 44% 15

-24% 23%

+35% 40% 14

+23% 35% 15

Note: Audited orphan drug NME count currently available from 2005+.
Copyright 2013 Evaluate Ltd. All rights reserved.

13

FDA New Drug Approval Analysis (NMEs/ BLAs) 2012: Orphan vs. Non Orphan
FDA New Drug Approval Analysis (NMEs/ BLAs) 2012: Orphan vs. Non Orphan
Kyprolis Most Promising New Orphan Drug Approved by FDA in 2012 Top 10 Orphan Drugs have 43% the Sales Potential of Non-Orphan but Delivered at 29% of the Phase III Trial Cost EvaluatePharma finds that Kyprolis, from Onyx, for multiple myeloma is the most promising new orphan drug approved in 2012, with expected US sales in 2017 of $897m. The top 10 orphan drugs approved in 2012 are expected to sell on average $392m in the USA market, five years post launch. This compares with $911m for non-orphans approved in 2012. The average Phase III trial size for the top 10 orphans was 592 patients vs 8,614 for top 10 non-orphans approved in 2012. Avg. USA Sales 5 Years After Launch (2012 FDA Approvals)
1,000 900 800 700 600 500 400 300 200 100 0 Orphan (Top 10) Non-Orphan (Top 10) 392 911 10,000 9,000 8,000 7,000 6,000 5,000 4,000 3,000 2,000 1,000 0 592 Orphan (Top 10) Non-Orphan (Top 10) 8,614

Avg. Phase III Trial Size (2012 FDA Approvals)

Top 10 Orphan New Molecular Entities approved in 2012: Ranked on USA Consensus Sales in 2017
Product 1 Kyprolis 2 Kalydeco 3 Iclusig 4 Jetrea 5 6 7 8 Signifor Inlyta Gattex Juxtapid OD Indication Company Approved
Jan 2012 Jul 2012

Cystic fibrosis

Multiple myeloma Acute lymphoblastic leukemia (Ph+ALL); CML Adjunct to surgery in cases of pediatric vitrectomy [R&D] Cushing's disease Renal cell carcinoma

Vertex Pharmaceuticals

Onyx Pharmaceuticals

US Sales 2012 2017

172 64 706 897

Phase III Trial Size

1,030 968 652 465 559

Cost ($m) 118 115 80

R&D PIII

ARIAD Pharmaceuticals ThromboGenics Novartis NPS Pharmaceuticals Pfizer

Dec 2012 Oct 2012 Dec 2012 Dec 2012 Dec 2012 May 2012 Sep 2012 Jan 2012

538 382 352

3 -

98 128 98

Short bowel syndrome Homozygous familial hypercholesterolemia Gaucher's disease

59 -

252

Aegerion Pharmaceuticals Pfizer

244

250

1,215 357 54

117 22

9 Elelyso 10 Bosulif Top 10 Other Total

Chronic myelogenous leukemia

Pfizer

310 325 14

3,916 3,977 62

147

148

5,924

502

122

901

76

50

Average for Top 10: As a % of non-orphans

392 43%

592 7%

29%

Top 10 Non-Orphan New Molecular Entities approved in 2012: Ranked on USA Consensus Sales in 2017
Product 1 Stribild 2 Eliquis 3 Xeljanz 4 Xtandi 5 Linzess 6 Perjeta 7 Tudorza Pressair 8 Belviq 9 Aubagio 10 Myrbetriq Top 10 Other Total Source: EvaluatePharma (23 APR 2013)
Copyright 2013 Evaluate Ltd. All rights reserved.

Bristol-Myers Squibb Pfizer Astellas Pharma Roche Eisai

Gilead Sciences

Company

Approved
Aug 2012 Dec 2012 Nov 2012 Aug 2012 Aug 2012 Jun 2012 Jun 2012 Jun 2012 Jul 2012

US Sales 2012 2017

58 -

18 29 23 6 9

1,923

1,959

Phase III Trial Size

34,647 9,117 2,879 1,408

Cost ($m) 135 950 276

R&D PIII

Forest Laboratories Forest Laboratories Sanofi

87

1,183 819 399

1,158 598 394 384 295

282

58

6,184 4,657 7,794 5,530 4,614

221 224 267 183 319

212

Astellas Pharma

Sep 2012

314 203 517

27

9,112 10,774 1,662

86,137

9,307

3,070

Average for Top 10:

911

8,614

14

EU Orphan Designations: Historic Distribution by Prevalence

EU Orphan Designations: Historic Distribution by Prevalence
18.5% of EU Orphan Designations for Ultra Rare Diseases EvaluatePharma found that 18.5% (198 out of 1,072) of EU Orphan drug designations are for an ultra rare orphan disease. An ultra rare designation is classed as having an EU prevalence of 10,000 or less individuals (0.20 per 10,000). In the ultra rare segment 23% (46) orphan drug designations were granted for designations with a prevalence of less than 500 individuals. At the other end of the prevalence scale just 2% (3) of designations were granted for diseases with a prevalence of 240,000 or more individuals. Historic Distribution of Orphan Drug Designations in the EU Source: EvaluatePharma (23 APR 2013)
100% 90% Percentage of EU Designations (%) 80% 70% Ultra Rare 60% 50% 40% 30% 20% 10% 0% 0 0.20 50000 0.99 100000 1.98 150000 2.96 200000 3.95 4.94 250000
% of Designations

Per 10,000 EU Population

Total EU Disease Prevalence Population

Distribution and Count of EU Orphan Designations Based on Prevalence

EU Prevalence 0 - 10,000 10,000 - 20,000 20,000 - 30,000 30,000 - 40,000 40,000 - 50,000 50,000 - 100,000 100,000 - 150,000 150,000 - 200,000 200,000 - 250,000 Total % of Total 18.5% 7.9% 8.5% 5.6% 12.4% 23.7% 12.6% 8.5% 2.3% 100.0% Cumulative % of Total 26.4% 34.9% 40.5% 52.9% 76.6% 89.2% 97.7% 100.0% Designation Count 198 85 91 60 133 254 135 91 25 1072

Source: EvaluatePharma (23 APR 2013)

Copyright 2013 Evaluate Ltd. All rights reserved.

Note: Based on available EU prevalence data for a specific designation, as of the 28th of February 2013. EU total population taken to be 506,300,000. EvaluatePharma used Alexion Pharmaceuticals' definition of an ultra rare orphan drug, disease affecting fewer than 20 individuals per million of population (0.2 per 10,000).

15

EU Orphan Designations: Top 20 Indications

EU Orphan Designations: Top 20 Indications
Acute Myeloid Leukaemia is Indication with Most Filed Orphan Drug Designations in EU EvaluatePharma finds that acute myeloid leukaemia is the indication with the most orphan designations in the EU. A number of blood malignancies appear in the top 20 including chronic and acute lymphocytic leukaemia (No. 10 & 11) and chronic myeloid leukaemia (No. 17). In fact, accounting for all of these, 8 indications out of the top 20 fall within EvaluatePharma's Blood and Blood Forming Malignancies categorization. Other notable indications include historically well defined populations and indications such as cystic fibrosis and Duchenne muscular dystrophy. Hodgkin lymphoma was the only indication in the top 20 to have an EU prevalence of less than 1.0. Top 20 EU Orphan Designations Source: EvaluatePharma (23 APR 2013)
Leukaemia, acute myeloid (AML)

Number of EU OD Designations
38 45

Non-Hodgkin lymphoma (NHL) Pancreatic cancer Ovarian cancer 28 Glioma 35 35

37

Cystic fibrosis (CF)

Renal cell carcinoma (RCC) Leukaemia, chronic lymphocytic (CLL) Leukaemia, acute lymphocytic (ALL) Duchenne muscular dystrophy Pulmonary hypertension

Multiple myeloma

27 21 27

Hepatoma, liver cancer

20 19 20

Graft vs host disease (GvHD) 16

18

Pulmonary fibrosis, idiopathic

Leukaemia, chronic myeloid (CML) Myelodysplastic syndrome Anaemia, sickle cell 0 5 Hodgkin Lymphoma 9 9

Soft tissue sarcoma

13 10 10 13

10

15

20

25

30

35

40

45

50

Number of EU OD Designations

Top 20 Orphan Drug Designation Indications in the EU

Rank Indication 2 4

Leukaemia, acute myeloid (AML) Glioma Non-Hodgkin lymphoma (NHL) Pancreatic cancer Ovarian cancer

Total EU Designations
45 38 37 35

As a % 4% 3% 3%

EU Prevalence (per 10,000) 2.4 1.6 3.5 3.5 2.2 1.3 3.2 4.2 4.0 2.7 1.0 2.2 1.2 3.0 3.0 1.6 0.52 2.5 2.4 2.5

3%

Cystic fibrosis (CF) Multiple myeloma

35

3%

28

11 12 14

10

Hepatoma, liver cancer

Renal cell carcinoma (RCC)

Leukaemia, acute lymphocytic (ALL) Duchenne muscular dystrophy Pulmonary fibrosis, idiopathic Soft tissue sarcoma Leukaemia, chronic myeloid (CML) Myelodysplastic syndrome Anaemia, sickle cell Hodgkin Lymphoma Pulmonary hypertension Graft vs host disease (GvHD)

Leukaemia, chronic lymphocytic (CLL)

21 20

27

27

2% 2% 2% 2% 2%

2%

3%

20

13

19

2%

15 16 17 19 18

13 13 10 10 9 9

16

18

1% 1% 1% 1%

1%

1% 1%

Copyright 2013 Evaluate Ltd. All rights reserved.

20

Sub Total Other Total

450 1097 647

41% 100% 59%

Source: EvaluatePharma (23 APR 2013)

Note: Designations assigned based on closest possible match to existing indications within EvaluatePharma. For example: EU Designation: Adult acute myeloid leukaemia with 11q23 (MLL) abnormalities is mapped to Leukaemia, acute myeloid (AML).

16

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Download this complimentary report at: www.evaluategroup.com/orphandrug2013. Please share this link with a colleague.
To find out more about the findings in this report and EvaluatePharmas orphan drug market intelligence, please contact:
North America: Japan:

Debbie Paul Tel: +1 617 573 9453 Email: debbie.paul@evaluategroup.com

Rest of the World :

Hiroshi Yamazaki Tel: + 81 (0) 80 1164 4754 Email: hiroshi.yamazaki@evaluategroup.com

 For general questions:

Will Hau Tel: +44 (0)20 7377 0800 Email: will.hau@evaluategroup.com

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Established in 1996, Evaluate is the leader in high quality life science sector analysis. EvaluatePharma delivers exclusive consensus forecasts and trusted commercial insight into biotech and pharmaceutical performance. EvaluateMedTech sets a new standard in integrated analysis and consensus forecasts of the global medical device and diagnostic industry. EvaluateClinical Trials delivers unique intelligence to efficiently and accurately analyze the global clinical trial landscape. A team of over 85 dedicated healthcare analysts employ rigorous methodologies to collate, organize and deliver the most-up-to-date commercial performance data available. An award-winning editorial team of journalists writing under the EP Vantage name support EvaluatePharmas analysis. The Evaluate services enable the life science community to make sound business decisions about value and opportunity.

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Copyright 2013 Evaluate Ltd. All rights reserved. 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 Evaluate Ltd. While all reasonable steps have been taken to ensure that the data presented are accurate, Evaluate Ltd. cannot accept responsibility for errors or omissions. Neither does Evaluate Ltd. warrant the accuracy, merchantability or fitness of use for a particular purpose of the data. ORPHANDRUG2