Generic Growth Strategies - Market Driven by Impending Patent Cliff, Declining R&D Productivity and Government Initiatives to Reduce Healthcare Costs

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Generic Growth Strategies - Market Driven by Impending Patent Cliff, Declining R&D Productivity and Government Initiatives to Reduce Healthcare Costs
Generic Growth Strategies

Market Driven by Impending Patent Cliff, Declining R&D Productivity and

Government Initiatives to Reduce Healthcare Costs

GBI Research Report Guidance









GBI Research Report Guidance

· Chapter three gives an overview of the generic pharmaceutical market. It includes a list of leading

generic pharmaceutical companies, the generic market share of select countries, and drivers and

restraints of the generic pharmaceutical market.

· Chapter four describes the regulatory landscape of the generic drugs industry in the US, major

European countries such as the UK, Germany, France, Italy and Spain, and Japan. This section details

the current and upcoming regulations that are expected to have an impact on the growth of the

generics market.

· Chapter five gives details of the major growth strategies adopted in the generics drugs industry. Case

studies accompany the strategies to show their real market impact.

· Chapter six is focused on competitive profiling. This section includes detailed profiles of the top

companies operating in the generics market, along with their generic growth strategies.









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Executive Summary









Executive Summary

Leading Generic Companies Resort to Multiple Strategies for Growth

Most of the leading generic giants such as Teva, Sandoz, Mylan and Watson use multiple options to ensure

a high market share and future growth. The strategies used include applying for generic approvals with the

Food and Drug Administration (FDA) and European Medicines Agency (EMA), Mergers and Acquisitions

(M&As), developing a strong and innovative generic drug pipeline, improving infrastructure to enhance

manufacturing and Research and Development (R&D) capabilities, new product launches, and geographic

expansion.

Generic and innovative pharmaceutical companies are exploring all of the ways available to increase their

presence in the generic pharmaceutical market, given the current scenario where governments are

encouraging the increased use of generics to bring down healthcare costs. For instance, Hospira is reaching

out to cover new geographies in order to develop their presence in generics across the world, and also

increasing their product coverage by offering generics that are available in the market but not included in

their product portfolio.

The advantage of being the first to launch a generic in the market has been capitalized on by companies

such as Hospira, by challenging the intellectual property of proprietary pharmaceutical companies. The

strategy has resulted in generating generic blockbusters, such as in the case of Sandoz’s generic enoxaparin.

With the regulatory landscape in biosimilars taking shape, many pharmaceutical companies are developing

biosimilars of potential reference biologics that are soon going off-patent.

Difficult-to-Reproduce Generics Being Developed to Beat Competition

Some of the generic companies are focusing on a new trend by offering generics that have high barriers to

entry and are as a result available at higher prices. These are called super generics, and are developed as

value-added reformulations of off-patent drugs that require New Drug Application (NDA) submissions.

Super generics offer a means of differentiation in the industry. For the development of super generics,

these companies have to invest in R&D to launch reformulated versions of off-patent drugs, or apply a

complex manufacturing process. Significant potential for super generics lies in specific therapeutic areas.

Super generics producers focus on areas of unmet medical needs that are not satisfied by the current

therapies, in high sales potential areas such as Central Nervous System (CNS) and cancer. Areas where

innovators have already patented extensively and developed several line extensions in easy-to-formulate

markets, such as cardiovascular drugs, have less attractiveness to super generics manufacturers.

There are several types of reformulation strategy that are adopted to make super generics out of off-patent

drugs, such as new dose forms (injection to oral forms, extended release), new combinations and new salts.

For instance, Dr. Reddy’s Laboratories (DRL) sells fondaparinux, which is the generic version of

GlaxoSmithKline’s (GSK) Arixtra, in the US. Alchemia develops the product with the help of a novel, cost-

effective synthesis for the manufacture of fondaparinux at commercial scale. The process is patent

protected until 2021 (fondaparinux product website, 2012). There is no risk of raw material contamination

with fondaparinux since it is a purely synthetic compound. Generic fondaparinux has a superior efficacy and

safety profile when compared to other heparin drugs. The bulk manufacturer, DRL, produces fondaparinux

at a reasonably competitive price in the US market.









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Executive Summary









Opportunities Worth More than $100 billion in Generics and Biosimilars

By 2015, branded products

with sales of up to $135 The looming drug patent expiration loss the industry is presently facing is unprecedented, in terms of both

billion will go off-patent, the number of drugs and the magnitude of the total hit. However, this same situation presents a huge

giving generic opportunity for the generic drug makers.

pharmaceutical companies The figure below is an illustration of the global revenues of the top 10 drugs that are set to lose their patent

immense opportunities to protection between 2013 and 2020.

capitalize on the market

Generic Growth Strategies, Global, Revenues of the Top 10 Drugs Due for Patent Expiry ($m), 2013-

2020



9,000



8,000



7,000



6,000

Revenues ($m)









5,000



4,000



3,000



2,000



1,000



0

Crestor









Abilify

Rituxan/mabThera

Enbrel









Lantus









Januvia/Janumet

Remicade









Avastin







Herceptin

Humira









Source: GBI Research; GBI Research’s Proprietary Products Database [accessed on: September 20, 2012]

Note: The patent of blockbuster drug Enbrel has been extended to 2028









The pharmaceutical industry will experience major patent expiries during 2013-2020, of which 2014 to 2017

are expected to be peak years, with the loss of patents for drugs whose sales were worth more than $76

billion during 2011. By 2015, branded products with sales of up to $135 billion will go off-patent, giving

generic pharmaceutical companies immense opportunities to capitalize on the market (Teva, 2011). Along

with generic drugs, pharmaceutical companies will also have the opportunity to develop biosimilars, as

biologics with 2011 sales of approximately $64 billion will go off-patent over the next five years (Novartis,

2012).









© GBI Research. This is a licensed product and is not to be photocopied GBIHC263MR / Published DEC 2012

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Executive Summary









Significant Increase in ANDA Applications and Approvals

In 2012, there were more

first-time generic drug The number of Abbreviated New Drug Applications (ANDAs) filed by generic companies has significantly

approvals when compared increased between 2006 and 2011, indicating upcoming generic competition.

to the corresponding months The figure below displays the number of generic ANDA approvals and filings between 2006 and 2011.

of 2011

Generic Growth Strategies, Number of Generic ANDA Filed and Approvals, 2006-2011



1,000

946

900 882 854

828

835 794

800



700



600



500



400



300



200

99 112

100 91 93

100 93



0

2006 2007 2008 2009 2010 2011



Generic ANDA filed Generic ANDA approvals



Source: GBI Research; FDA, 2012a









Available data from the FDA shows that the number of ANDAs submitted for generic drugs has increased

significantly during the past two years.

In 2012, there were more first-time generic drug approvals when compared to the corresponding months of

2011. For instance, there were 23 ANDA approvals in March 2012, which is significantly higher when

compared to two ANDA approvals in March 2011. Similarly, May 2012 saw 32 approvals in comparison to

only nine approvals in May 2011. If the trend continues, 2012 may witness higher approvals than 2011, as

the total number of approvals has already reached 76 for 2012 (as of July 26, 2012), which is only marginally

lower than the total of 93 approvals in 2011 (FDA, 2012c).









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Executive Summary









Government Initiatives for Generics Strengthen as Healthcare Costs Increase

The 2012 budget of the US proposes to ban the controversial ‘pay-for-delay’ type of agreements between

innovator and generic drug makers. The Federal Trade Commission (FTC) estimates that a pay-for-delay ban

would cut deficits by $2.7 billion over 10 years (PharmaTimes, press release, October 26, 2011). The budget

has also proposed to reduce patent protection on brand-name biologics from the current 12 years to seven

years, with a view to benefiting consumers by hastening the introduction of biosimilars and increasing

healthcare savings (Barlas, 2011).

According to the Affordable Care Act (ACA), the generic drug costs paid by non-Low Income Subsidy (LIS)

beneficiaries in the Medicare Part D (MPD) coverage gap will gradually reduce from 86% in 2012 to 25% in

2020. The majority of cost sharing will be undertaken by the MPD plan as it will pay 75% of the generic drug

costs by 2020 (Medicare, 2012).

On February 15, 2012, the FDA issued three guidance documents that are intended to provide a roadmap

for biosimilar development. In June 2012, the EMA laid out guidelines regarding requirements for

developing biosimilar monoclonal antibodies (mAb).

The Italian government set out a series of measures as part of its major austerity package to save €24 billion

($31.8 billion) by cutting expenditure on medicines by approximately €1.3 billion ($1.7 billion) from 2010 to

2012 (RIA Novosti, press release, December 5, 2011). In Spain, a Royal Law Decree was introduced in August

2011 that mandates prescription by molecule rather than by brand. The decree may enhance generic

penetration in the Spanish market. The decree will help the state and the autonomous regions save a total

of €2.4 billion ($3.1 billion) per year in medicines (Bloomberg, press release, July 2, 2012). The Japanese

government has started promoting generic name prescribing, and has established a financial incentive

scheme that encourages pharmacies to substitute generic drugs for branded ones, to increase generic

penetration to 30% by 2012 or March 2013 (Ministry of Health, Labor and Welfare, 2012).









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Table of Contents









1 Table of Contents

1 Table of Contents ........................................................................................................................................ 7

1.1 List of Tables .................................................................................................................................. 10

1.2 List of Figures................................................................................................................................. 10

2 Generic Growth Strategies - Introduction ................................................................................................. 11

3 Generic Growth Strategies - Market Overview ......................................................................................... 12

3.1 Overview of the Generics Market ................................................................................................. 12

3.1.1 Leading Generics Companies................................................................................................. 12

3.1.2 Generics Market Share .......................................................................................................... 14

3.2 Drivers and Restraints ................................................................................................................... 15

3.2.1 Drivers ................................................................................................................................... 16

3.2.2 Restraints .............................................................................................................................. 21

4 Generic Growth Strategies - Regulatory Landscape .................................................................................. 23

4.1 The US ........................................................................................................................................... 23

4.1.1 Hatch-Waxman Act and ANDA .............................................................................................. 23

4.1.2 Shortening Market Exclusivity of Biopharmaceuticals and Impact on Generics .................... 25

4.1.3 ‘Pay-For-Delay’ Ban to be Detrimental to Innovators as Well as Generics ............................ 25

4.1.4 Cost-sharing of Generic Drugs ............................................................................................... 25

4.1.5 Impact of Supplemental Examination Provision of Patent Reform Act on Generics .............. 26

4.1.6 Biologics Price Competition and Innovation Act Falls Short .................................................. 26

4.2 Europe ........................................................................................................................................... 28

4.2.1 Generic Penetration .............................................................................................................. 28

4.2.2 Generic Substitution .............................................................................................................. 29

4.2.3 Pricing and Reimbursement .................................................................................................. 29

4.2.4 Marketing Authorization for Generics ................................................................................... 29

4.2.5 Generic Landscape in Leading European Markets ................................................................. 29

4.2.6 Common European Union Patent System.............................................................................. 31

4.2.7 Tendering .............................................................................................................................. 32

4.2.8 Regulatory Landscape for Biosimilars ................................................................................... 32

4.2.9 The Future of Biosimilars is Advancing Along a Path Smoothened by European Groundwork

.............................................................................................................................................. 32

4.3 Japan ............................................................................................................................................. 33

4.3.1 Generics................................................................................................................................. 33

4.3.2 Biosimilar............................................................................................................................... 34

5 Generic Growth Strategies - Major Strategies .......................................................................................... 35

5.1 Authorized Generics ...................................................................................................................... 35

5.1.1 Case Study ............................................................................................................................. 37

5.2 Mergers and Acquisitions .............................................................................................................. 37

5.2.1 Vertical Integration ............................................................................................................... 39

5.2.2 Therapeutic Expansion - Biosimilars ...................................................................................... 39

5.3 Outsourcing ................................................................................................................................... 40

5.3.1 Outsourcing Opportunities in Biosimilars .............................................................................. 40

5.3.2 Outsourcing is Also a Source of Income for Generics Companies .......................................... 40

5.4 Marketing Partnership .................................................................................................................. 41

5.4.1 Case Studies .......................................................................................................................... 41

5.5 Paragraph IV Certifications ............................................................................................................ 42

5.5.1 Case Studies .......................................................................................................................... 42

5.5.2 Example of a Paragraph IV Challenge That Did Not Work Out for a Generic ........................ 42

5.6 R&D Strategies Employed by Key Players in the Generics Market ................................................ 43

5.6.1 Super Generics....................................................................................................................... 43

5.6.2 Biosimilars ............................................................................................................................. 44





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Table of Contents









5.7 Increasing Awareness and Acceptance ......................................................................................... 46

6 Generic Growth Strategies - Competitive Landscape................................................................................ 47

6.1 Teva Pharmaceutical Industries Limited ........................................................................................ 47

6.1.1 Overview ............................................................................................................................... 47

6.1.2 Revenue Analysis ................................................................................................................... 47

6.1.3 Therapeutic Focus ................................................................................................................. 48

6.1.4 Geographic Focus .................................................................................................................. 48

6.1.5 Generic Growth Strategies .................................................................................................... 48

6.1.6 SWOT..................................................................................................................................... 51

6.2 Sandoz ........................................................................................................................................... 52

6.2.1 Overview ............................................................................................................................... 52

6.2.2 Revenue Analysis ................................................................................................................... 52

6.2.3 Therapeutic Focus ................................................................................................................. 52

6.2.4 Geographic Focus .................................................................................................................. 52

6.2.5 Generic Growth Strategies .................................................................................................... 53

6.2.6 SWOT..................................................................................................................................... 54

6.3 Mylan............................................................................................................................................. 55

6.3.1 Overview ............................................................................................................................... 55

6.3.2 Revenue Analysis ................................................................................................................... 55

6.3.3 Therapeutic Focus ................................................................................................................. 55

6.3.4 Geographic Focus .................................................................................................................. 55

6.3.5 Generic Growth Strategies .................................................................................................... 57

6.3.6 SWOT..................................................................................................................................... 58

6.4 Watson .......................................................................................................................................... 59

6.4.1 Overview ............................................................................................................................... 59

6.4.2 Revenue Analysis ................................................................................................................... 59

6.4.3 Therapeutic Focus ................................................................................................................. 59

6.4.4 Geographic Focus .................................................................................................................. 59

6.4.5 Generic Growth Strategies .................................................................................................... 60

6.4.6 SWOT..................................................................................................................................... 61

6.5 Actavis ........................................................................................................................................... 62

6.5.1 Overview ............................................................................................................................... 62

6.5.2 Revenue Analysis ................................................................................................................... 62

6.5.3 Therapeutic Focus ................................................................................................................. 62

6.5.4 Geographic Focus .................................................................................................................. 62

6.5.5 Generic Growth Strategies .................................................................................................... 62

6.5.6 SWOT..................................................................................................................................... 63

6.6 Hospira .......................................................................................................................................... 64

6.6.1 Overview ............................................................................................................................... 64

6.6.2 Revenue Analysis ................................................................................................................... 64

6.6.3 Therapeutic Focus ................................................................................................................. 64

6.6.4 Geographic Focus .................................................................................................................. 64

6.6.5 Generic Growth Strategies .................................................................................................... 65

6.6.6 SWOT..................................................................................................................................... 66

6.7 Sanofi............................................................................................................................................. 67

6.7.1 Overview ............................................................................................................................... 67

6.7.2 Revenue Analysis ................................................................................................................... 67

6.7.3 Geographic Focus .................................................................................................................. 67

6.7.4 Generic Growth Strategies .................................................................................................... 67

6.7.5 SWOT..................................................................................................................................... 68

6.8 Daiichi Sankyo ............................................................................................................................... 68

6.8.1 Overview ............................................................................................................................... 68





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Table of Contents









6.8.2 Revenue Analysis ................................................................................................................... 68

6.8.3 Geographic Focus .................................................................................................................. 68

6.8.4 Generic Growth Strategies .................................................................................................... 68

6.8.5 SWOT..................................................................................................................................... 69

6.9 Aspen ............................................................................................................................................. 69

6.9.1 Overview ............................................................................................................................... 69

6.9.2 Revenue Analysis ................................................................................................................... 69

6.9.3 Geographic Focus .................................................................................................................. 69

6.9.4 Generic Growth Strategies .................................................................................................... 70

6.9.5 SWOT..................................................................................................................................... 70

6.10 STADA ............................................................................................................................................ 71

6.10.1 Overview ............................................................................................................................... 71

6.10.2 Revenue Analysis ................................................................................................................... 71

6.10.3 Therapeutic Focus ................................................................................................................. 71

6.10.4 Geographic Focus .................................................................................................................. 71

6.10.5 Generic Growth Strategies .................................................................................................... 72

6.10.6 SWOT..................................................................................................................................... 72

7 Generic Growth Strategies - Conclusion ................................................................................................... 73

8 Generic Growth Strategies - Appendix ...................................................................................................... 74

8.1 Market Definitions......................................................................................................................... 74

8.2 Abbreviations ................................................................................................................................ 74

8.3 Bibliography .................................................................................................................................. 75

8.4 Research Methodology ................................................................................................................. 77

8.4.1 Coverage ............................................................................................................................... 77

8.4.2 Secondary Research .............................................................................................................. 77

8.4.3 Primary Research .................................................................................................................. 78

8.4.4 Expert Panel Validation ......................................................................................................... 78

8.5 Contact Us ..................................................................................................................................... 78

8.6 Disclaimer ...................................................................................................................................... 78









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Table of Contents









1.1 List of Tables

Table 1: Generic Growth Strategies, Global, Revenues of Leading Generic Companies ($bn), 2010-2011 13

Table 2: Generic Growth Strategies, Global, Revenues of Major Drugs Due for Patent Expiry ($m), 2013-

2020.............................................................................................................................................. 17

Table 3: Generic Growth Strategies, Number of Generic ANDA Filed and Approvals, 2006-2011 ............. 18

Table 4: Generic Growth Strategies, ANDA Approvals by Month, The US, 2011-2012 .............................. 19

Table 5: Generic Growth Strategies, Number of EMA Authorized Generics, Europe, 2007-2012.............. 20

Table 6: Generic Growth Strategies, Number of Biosimilars Authorized by the EMA, Europe, 2006-2012 22

Table 7: Generic Growth Strategies, The US, Generic Drug Cost-Sharing (%), 2011-2020 ......................... 26

Table 8: Generic Growth Strategies, Notable Authorized Generics Entry, The US, 2010-2012.................. 35

Table 9: Generic Growth Strategies, Generic Products Launched, Teva, The US, 2011 ............................. 49

Table 10: Generic Growth Strategies, Top Five Generic Active Ingredients, STADA Group, Revenue ($m),

2011.............................................................................................................................................. 71





1.2 List of Figures

Figure 1: Generic Growth Strategies, Global, Revenues of Leading Generic Companies ($bn), 2010-2011 13

Figure 2: Generic Growth Strategies, Generic Market Share in Selected Countries, 2010 .......................... 14

Figure 3: Generic Growth Strategies, Drivers and Restraints, 2012 ............................................................ 15

Figure 4: Generic Growth Strategies, Global, Revenues of Top 10 Drugs Due for Patent Expiry ($m), 2013-

2020.............................................................................................................................................. 16

Figure 5: Generic Growth Strategies, Number of Generic ANDA Filed and Approvals, 2006-2011 ............. 18

Figure 6: Generic Growth Strategies, ANDA Approvals by Month, The US, 2011-2012 .............................. 19

Figure 7: Generic Growth Strategies, Number of EMA Authorized Generics, Europe, 2007-2012.............. 20

Figure 8: Generic Growth Strategies, Number of Biosimilars Authorized by the EMA, Europe, 2006-2012 22

Figure 9: Generic Growth Strategies, The US, Generic Drug Cost-Sharing (%), 2011-2020 ......................... 25

Figure 10: Generic Growth Strategies, SWOT Analysis, Teva, 2012 .............................................................. 51

Figure 11: Generic Growth Strategies, SWOT Analysis, Sandoz, 2012 .......................................................... 54

Figure 12: Generic Growth Strategies, SWOT Analysis, Mylan, 2012 ............................................................ 58

Figure 13: Generic Growth Strategies, SWOT Analysis, Watson, 2012.......................................................... 61

Figure 14: Generic Growth Strategies, SWOT Analysis, Actavis, 2012........................................................... 63

Figure 15: Generic Growth Strategies, SWOT Analysis, Hospira, 2012 .......................................................... 66

Figure 16: Generic Growth Strategies, SWOT Analysis, Sanofi, 2012 ............................................................ 68

Figure 17: Generic Growth Strategies, SWOT Analysis, Daiichi Sankyo, 2012 ............................................... 69

Figure 18: Generic Growth Strategies, SWOT Analysis, Aspen, 2012 ............................................................ 70

Figure 19: Generic Growth Strategies, SWOT Analysis, STADA Arzneimittel AG, 2012 ................................. 72









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Generic Growth Strategies: Introduction









2 Generic Growth Strategies - Introduction

Generic drugs have the same active ingredient as their corresponding innovative drugs, and are therefore

an equivalent but cheaper therapeutic option compared to innovative drugs, due to less cost and time being

required in their development process.

Generic drugs need to meet similar governmental regulatory requirements as those for innovative drugs,

and should be approved by regulatory authorities to be sold in particular countries. The demand for generic

drugs is growing continuously due to the need to control rising healthcare expenditure, particularly with

regard to the increasing elderly population.

In the US, generic drugs can cost up to 90% less than branded drugs (Federal Trade Commission, 2010).

Generics bring relief to payers by lowering healthcare costs. Meanwhile, demand for high-quality generics is

expected to increase in the future, with a number of branded drugs going off-patent. The use of generics

has saved the US healthcare system over $1 trillion from 2000 through 2010 (Generic Pharmaceutical

Association (GPhA), press release, August 2, 2012).

In ‘pure generic’ markets such as the US, the UK, the Netherlands and Israel, generic pharmaceuticals are

substituted by the pharmacist for their brand name equivalent. In these markets, physicians or patients

have little control over the choice of generic manufacturer. Moreover, generic drugs are not actively

promoted to physicians, and the relationship between the generic manufacturer, pharmacy chains,

distributors, health funds, and other health insurers is important.

In ‘branded generic’ markets such as Poland,

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