Nanotechnology in Drug Delivery Technological Improvements and Novel Approaches to Fulfill High Po

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Nanotechnology in Drug Delivery Technological Improvements and Novel Approaches to Fulfill High Po
Nanotechnology in Drug Delivery - Technological

Improvements and Novel Approaches to Fulfill High Potential

Reference Code: GBIHC043MR Publication Date: December 2010





The nano-enabled drug delivery market has seen high growth in the market and is expected to

grow at a faster rate in the near future. The market will witness increased competition, high

High unmet need in the investment from venture capitalists and government. The M&A and licensing landscape will see

nano-enabled drug significant changes in the future. This is because the market is expected to become more lucrative.

delivery market offers

tremendous scope for new The Nano-Enabled Market Represents Significant Opportunities and High Level of Unmet

entrants and existing Needs

players

Nanotechnology in Drug Delivery Market, Opportunity and Unmet Needs, 2010





Opportunities Unmet Needs



Opportunities for

Nanotoxicity of

New Dug Delivery

Nanomaterials

Companies









Need of

Market Growth Opportunity and Understanding

Unmet Needs Biological behavior









Need of

Understanding

Licensing Distribution Pattern

Opportunity of Nanomaterials









Source: GBI Research









The nano-enabled drug delivery market has plenty of opportunities and a high level of unmet need.

Opportunities for creating a new drug delivery company are tremendous. Many small companies

have launched the technology to develop novel methods for exploiting nanotechnologies in drug

delivery. In the past, companies have been dedicated to the nano-enabled drug delivery that has

been popping up all over the world.

The creation of new companies will not only increase the investment and market growth, but also

increase the competition in the market place. In addition, the emergence of new companies will

provide licensing and merger and acquisition (M&A) opportunities for larger pharmaceutical

markets.

The market is also characterized by high levels of unmet need. This is primarily because

development in this area is in its initial stages and has a significant number of unaddressed issues

such as nanotoxicity, biological behavior and distribution pattern of nanoparticles. These unmet

needs represent a significant opportunity for companies to explore.





Nanotechnology in Drug Delivery - Technological Improvements GBIHC043MR / Published DEC 2010

and Novel Approaches to Fulfill High Potential

Page 1

© GBI Research. This is a licensed product and is not to be photocopied

In summary, high growth in the nano-enabled drug delivery markets will provide significant

opportunities for companies.

Increased Investment and Emerging Business Models Will Support the Market Growth

The increasing investment in the nano-enabled drug delivery market has significantly driven the

market. Funding for nanotechnology programs increased during the administration of George Bush.

The nanotechnology funding is expected to increase significantly in the future. Among all the major

geographies, the European government is investing more in nanotechnology R&D. This suggests

that there will be increased governmental support for nanotechnology R&D. In addition, increase in

early stage venture capital will also affect the market positively.

Careful Approach of Regulator towards Nanotechnology is Negatively Affecting the Market



Challenges Facing Regulators Regarding Nanotechnology









Address Promote Growth

Concerns in

Related Nanotechnology

to Health and

Environment









Assess whether

Finding Criteria New Regulations

for Segregating Regulatory Challenges are Required or

Nanoparticles in Nanotechnology Not









Regulations Co-operation

across the Globe between

should be Domestic

in-sync Regulators









Source: GBI Research









The toxicity increases due to increased surface area for the particle when the size is reduced. This

gives rise to concerns about the possible negative impact on public health and environment due to

increased use of nanotechnology enabled products. Nanotechnology is increasingly being

employed in industries such as medicine, cosmetics, food, semiconductor devices, energy and

telecommunications due to the advantages it provides over the conventional technology. As the

use of nanotechnology progresses, the risk of exposure to the population also rises. This has led a

cautious approach of regulators toward nanotechnology.









Nanotechnology in Drug Delivery - Technological Improvements GBIHC043MR / Published DEC 2010

and Novel Approaches to Fulfill High Potential

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1 Table of Contents

1 Table of Contents ........................................................................................................................ 3

1.1 List of Tables..................................................................................................................... 6

1.2 List of Figures ................................................................................................................... 6

2 Nanotechnology in Drug Delivery – Introduction.......................................................................... 7

2.1 Introduction ....................................................................................................................... 7

2.2 GBI Research Report Guidance ....................................................................................... 8

3 Application of Nanotechnology in Drug Delivery .......................................................................... 9

3.1 Current Applications of Nano-enabled Drug Delivery........................................................ 9

3.1.1 Nano-engineered drugs ............................................................................................. 9

3.1.2 Nano-carriers ........................................................................................................... 10

3.2 Future Applications of Nano-enabled Drug Delivery ....................................................... 11

3.2.1 Gene and Vaccine Delivery ..................................................................................... 11

3.2.2 Controlled-Release Devices .................................................................................... 12

3.2.3 Increased Biocompatibility ....................................................................................... 12

3.2.4 Improved Drug Bioavailability and Solubility ............................................................ 12

3.2.5 Applied Diagnosis, Etiology, Prognosis and Therapy (ADEPT) ............................... 12

3.2.6 Tissue Specific Delivery .......................................................................................... 12

4 Nanotechnology in Drug Delivery – Case Studies ..................................................................... 13

4.1 Abraxis Bioscience, Inc. – Paclitaxel-Albumin Nanoparticles (Abraxane) ....................... 13

4.2 Nanospectra Biosciences– AuroShell Particles .............................................................. 13

4.3 Calando Pharmaceuticals, Inc. – RONDEL Technology ................................................. 13

4.4 Starpharma Holdings, Ltd. – Dendrimer-Based VivaGel ................................................. 14

4.5 Mersana Therapeutics: Fleximer – Camptothecin Conjugate ......................................... 14

4.6 Elan Corporation – NanoCrystal Technology .................................................................. 14

5 Nanotechnology in Drug Delivery – Market Characterization .................................................... 16

5.1 Introduction ..................................................................................................................... 16

5.2 Nano-enabled Drug Delivery Market Drivers................................................................... 16

5.2.1 Clinical Benefits of Nano-enabled Drug delivery...................................................... 16

5.2.2 Value Addition to Existing Pharmaceutical Products through Reformulation ........... 16

5.2.3 Strong Pipeline Portfolio .......................................................................................... 16

5.3 Nano-Enabled Drug Delivery Market Barriers ................................................................. 17

5.3.1 Poor R&D Facilities and Time Gap between Research and Commercialization ...... 17

5.3.2 Lack of Consistent Policy on Technology Transfer and Lack of Capacity to Produce

Products .................................................................................................................. 17

5.3.3 Regulatory Hindrance .............................................................................................. 17

5.4 Opportunity and Unmet Need – Drug Delivery ................................................................ 18

5.4.1 Opportunities ........................................................................................................... 18

5.4.2 Unmet Need ............................................................................................................ 18

5.5 Selected Nano-Enabled Therapeutics Approved by the FDA ......................................... 20

5.5.1 Doxil (Caelyx) .......................................................................................................... 20

5.5.2 Abraxane ................................................................................................................. 21

5.5.3 AmBisome ............................................................................................................... 22

5.5.4 Diprivan ................................................................................................................... 23

5.5.5 Triglide ..................................................................................................................... 24

5.5.6 Myocet ..................................................................................................................... 25

5.5.7 DepoCyt .................................................................................................................. 26

5.5.8 DaunoXome............................................................................................................. 27

5.5.9 Estrasorb ................................................................................................................. 27

5.5.10 Macugen .................................................................................................................. 28

5.5.11 Abelcet .................................................................................................................... 29

5.5.12 Adagen .................................................................................................................... 30

5.5.13 Pegasys ................................................................................................................... 30

5.5.14 Somavert ................................................................................................................. 32





Nanotechnology in Drug Delivery - Technological Improvements GBIHC043MR / Published DEC 2010

and Novel Approaches to Fulfill High Potential

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5.5.15 Neulasta .................................................................................................................. 33

5.5.16 Copaxone ................................................................................................................ 34

5.5.17 Amphotec ................................................................................................................ 35

5.5.18 PegIntron ................................................................................................................. 35

5.5.19 Oncaspar ................................................................................................................. 37

5.5.20 Epaxal ..................................................................................................................... 38

5.5.21 Elestrin .................................................................................................................... 38

6 Nanotechnology in Drug Delivery – Trend Analysis................................................................... 40

6.1 Increasing Government Funding for Nanotechnology R&D ............................................ 40

6.2 Increasing Seed and Early-Stage Venture Capital .......................................................... 40

6.3 Creation of a New Registration Category for Nanotechnology Products within the USPTO

........................................................................................................................................ 40

6.4 Genericization and Emerging Business Models Driving a Need for Novel Drug Delivery

Methods .......................................................................................................................... 41

7 Nanotechnology in Drug Delivery – Regulatory Landscape ...................................................... 42

7.1 Introduction ..................................................................................................................... 42

7.2 Europe ............................................................................................................................ 44

7.2.1 REACH Regulation .................................................................................................. 44

7.2.2 European Medicines Agency ................................................................................... 46

7.3 The US ............................................................................................................................ 46

7.3.1 Environment Protection Agency .............................................................................. 46

7.3.2 Food and Drug Administration ................................................................................. 47

7.3.3 National Institute of Occupational Safety and Health............................................... 47

7.4 Japan .............................................................................................................................. 48

8 Nanotechnology in Drug Delivery – Pipeline Analysis ............................................................... 49

8.1 Overview ......................................................................................................................... 49

8.1.1 Pipeline Analysis by Phase ..................................................................................... 50

9 Nanotechnology in Drug Delivery – Strategic Consolidations .................................................... 55

9.1 Overview ......................................................................................................................... 55

9.2 Mergers and Acquisitions ................................................................................................ 55

9.2.1 Mergers and Acquisitions by Geography ................................................................. 55

9.2.2 Mergers and Acquisitions by Deal value.................................................................. 56

9.2.3 Mergers and Acquisition Analysis by Deal Type ...................................................... 57

9.3 Summary of Major M&A Deals ........................................................................................ 58

9.3.1 AstraZeneca Acquires MedImmune ........................................................................ 58

9.3.2 Pfizer Completes Acquisition of Wyeth .................................................................... 58

9.3.3 Celgene Announces To Acquire Abraxis BioScience .............................................. 58

9.3.4 Amgen Acquires Abgenix ........................................................................................ 59

9.3.5 Teva Pharmaceutical Acquires Ivax ........................................................................ 59

9.4 Licensing Agreement ...................................................................................................... 60

9.4.1 Deals by Year of Consolidations.............................................................................. 60

9.4.2 Deals by Geography ................................................................................................ 61

9.4.3 Deals by Deal value................................................................................................. 62

9.5 Summary of Major M&A Deals ........................................................................................ 62

9.5.1 AstraZeneca Enters Into Collaboration and Licensing Agreement with Targacept .. 62

9.5.2 AstraZeneca Enters into Licensing Agreement with Rigel Pharmaceuticals............ 63

9.5.3 Isis Pharmaceuticals Enters Into Licensing Agreement with Genzyme ................... 63

9.5.4 Nektar Therapeutics Enters Into Licensing Agreement with AstraZeneca ............... 63

9.5.5 Abraxis Enters Into License Agreement With ProMetic Life Sciences ..................... 64

10 Nanotechnology in Drug Delivery – Future Players ................................................................... 65

10.1 Overview ......................................................................................................................... 65

10.2 Abraxis Bioscience (Abraxis) .......................................................................................... 66

10.2.1 Overview ................................................................................................................. 66

10.2.2 Business Description ............................................................................................... 66

10.2.3 Product Portfolio ...................................................................................................... 67





Nanotechnology in Drug Delivery - Technological Improvements GBIHC043MR / Published DEC 2010

and Novel Approaches to Fulfill High Potential

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10.3 AlphaRx Corporation....................................................................................................... 68

10.3.1 Overview ................................................................................................................. 68

10.3.2 Business Description ............................................................................................... 68

10.3.3 Product Portfolio ...................................................................................................... 69

10.4 Camurus AB.................................................................................................................... 69

10.4.1 Overview ................................................................................................................. 69

10.4.2 Product Portfolio ...................................................................................................... 70

10.5 Eurand ............................................................................................................................ 70

10.5.1 Overview ................................................................................................................. 70

10.5.2 Business Description ............................................................................................... 70

10.5.3 Product Portfolio ...................................................................................................... 71

10.6 NanoBio Corporation ...................................................................................................... 71

10.6.1 Overview ................................................................................................................. 71

10.6.2 Product Portfolio ...................................................................................................... 72

10.7 NanoCarrier .................................................................................................................... 72

10.7.1 Overview ................................................................................................................. 72

10.7.2 Product Portfolio ...................................................................................................... 73

11 Nanaotechnology in Drug Delivery – Appendix ......................................................................... 74

11.1 Market Definitions ........................................................................................................... 74

11.2 Abbreviations .................................................................................................................. 74

11.3 Research Methodology ................................................................................................... 75

11.3.1 Coverage ................................................................................................................. 76

11.3.2 Secondary Research ............................................................................................... 76

11.3.3 Primary Research .................................................................................................... 76

11.3.4 Expert Panel Validation ........................................................................................... 77

11.4 Contact Us ...................................................................................................................... 77

11.5 Disclaimer ....................................................................................................................... 77

11.6 Sources ........................................................................................................................... 77









Nanotechnology in Drug Delivery - Technological Improvements GBIHC043MR / Published DEC 2010

and Novel Approaches to Fulfill High Potential

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1.1 List of Tables

Table 1: Elan Pharmaceutical, Drugs Based on NanoCrystal Technology, 2010 ............................ 15

Table 2: Nanotechnology in Drug Delivery, Global, Regulatory Filing Clinical Pipeline, 2010 ........ 50

Table 3: Nanotechnology in Drug Delivery, Global, Phase III Clinical Pipeline, 2010 .................... 51

Table 4: Nanotechnology in Drug Delivery, Global, Phase II Clinical Pipeline, 2010 ..................... 51

Table 5: Nanotechnology in Drug Delivery, Global, Phase I Clinical Pipeline, 2010 ...................... 52

Table 6: Nanotechnology in Drug Delivery, Global, Preclinical Pipeline, 2010 ............................... 53

Table 7: Nanotechnology in Drug Delivery, Global, Discovery Pipeline, 2010 ............................... 54

Table 8: Abraxis BioScience, Inc., Nano-Enabled Drug Delivery Pipeline Products, 2010.............. 67

Table 9: AlphaRx Corporation, Inc., Nano-enabled Drug Delivery Pipeline Products, 2010.......... 69

Table 10: Camurus AB, Inc., Nano-enabled Drug Delivery Pipeline Products, 2010 ..................... 70

Table 11: Eurand, Inc., Nano-enabled Drug Delivery Pipeline Products, 2010 .............................. 71

Table 12: NanoBio Corporation, Inc., Nano-enabled Drug Delivery Pipeline Products, 2010 ........ 72

Table 13: NanoCarrier, Inc., Nano-enabled Drug Delivery Pipeline Products, 2010 ...................... 73





1.2 List of Figures

Figure 1: Nanotechnology in Drug Delivery, Comparison of General and Nano-enabled Drugs,

2010 ................................................................................................................................. 7

Figure 2: Nanotechnology in Drug Delivery, Current Application of Nanotechnology in the

Pharmaceutical Industry, 2010 ......................................................................................... 9

Figure 3: Nanotechnology in Drug Delivery, Future Application of Nanotechnology in Drug

Pharmaceutical Industry, 2010 ....................................................................................... 11

Figure 4: Nanotechnology in Drug Delivery, Global, Driver and Restraints, 2010 ........................... 17

Figure 5: Nanotechnology in Drug Delivery, Opportunity and Unmet Needs, 2010......................... 19

Figure 6: Nanotechnology in Drug Delivery, Trend Analysis, 2010 ................................................. 40

Figure 7: Nanotechnology in Drug Delivery, Challenges Facing Regulators Regarding

Nanotechnology ............................................................................................................. 43

Figure 8: Nanotechnology in Drug Delivery, Global, Pipeline by Therapy Area (%), 2010 .............. 49

Figure 9: Nanotechnology in Drug Delivery, Global, Pipeline by Phase (%), 2010 ......................... 50

Figure 10: Nanotechnology in Drug Delivery, Global, M&A Deals by Geography (%), (2006-2010)

....................................................................................................................................... 55

Figure 11: Nanotechnology in Drug Delivery, Global, M&A Deals by Deals Value (%), 2006-201056

Figure 12: Nanotechnology in Drug Delivery, Global, M&A Deals by Deals Type (%), 2006-2010 57

Figure 13: Nanotechnology in Drug Delivery, Global, Licensing Agreements by Years of

Consolidation (%), 2006-2010 ........................................................................................ 60

Figure 14: Nanotechnology in Drug Delivery, Global, Licensing Agreements by Geography (%),

2006-2010 ...................................................................................................................... 61

Figure 15: Nanotechnology in Drug Delivery, Global, Licensing Agreements by Deals Value (%),

2006-2010 ...................................................................................................................... 62

Figure 16: Nanotechnology in Drug Delivery, Global, Clinical Pipeline by Company, 2010 ............ 65









Nanotechnology in Drug Delivery - Technological Improvements GBIHC043MR / Published DEC 2010

and Novel Approaches to Fulfill High Potential

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2 Nanotechnology in Drug Delivery – Introduction

2.1 Introduction

Nanotechnology witnesses a lot of attention with the never-seen-before interest because of its

future growth potential. This is because it can revolutionize the areas in which it is being exploited.

In the pharmaceutical market, nanotechnology is just starting to make an impact. The application of

nanotechnology in drug delivery systems has the ability to manipulate molecules for manufacturing

devices with programmed functions. The current pharmaceutical market has many drugs, which

use nanotechnology in their drug delivery approaches. These nano-enabled systems include

liposomes, polymeric micelles, nanoparticles, dendrimers, and nanocrystals.

Liposomes and polymer micelles were first prepared in 1960’s. Following this, nanoparticles and

dendrimers were prepared in the 1970’s. The conjugation of colloidal gold particles with antibody to

target specific staining during 1980’s, is considered as a precursor of recent widespread use of

gold particles in nanotechnology.

GBI research analysis suggests that the nano-enabled drug delivery market will witness a high

growth in the future. The high growth in the nano-enabled drug delivery market is primarily because

of increasing acceptance of nano-enabled drugs, promising nano-enabled drugs in the pipeline

portfolio and increased governmental funding in the nanotechnology research. In addition to these,

rapidly increasing interest in nanotech R&D, and increased availability of seed and early-stage

venture capital will drive the market during the forecast period.

GBI Research analysis shows that significant opportunities exist at the intersection of

nanotechnology and traditional pharmaceutical R&D, though much uncertainty remains on how this

will affect the industry. GBI Research suggests the dosing benefits of nano-enabled drug delivery

systems have a great potential in treating both infectious disease and cancer.



Figure 1: Nanotechnology in Drug Delivery, Comparison of General and Nano-enabled

Drugs, 2010





Parameters General Drug Nano-Enabled Drug





Bioavailability Low High





Specificity

Low High







Solubility Low Improved





Efficacy Low High





Safety Low High





Liver and Renal Toxicity Low High







Pharmacokinetics Low Improved





Patients Compliance Low High







Source: GBI Research









Nanotechnology in Drug Delivery - Technological Improvements GBIHC043MR / Published DEC 2010

and Novel Approaches to Fulfill High Potential

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© GBI Research. This is a licensed product and is not to be photocopied

2.2 GBI Research Report Guidance

· The report starts with an executive summary of the key points influencing the global nano-

enabled drug delivery market.

· The chapter titled Nanotechnology in Drug Delivery details the current and future potential

application of nanotechnology in drug delivery systems.

· The next chapter analyzes the major nano-enabled drug delivery technology case studies.

· The chapter titled Nanotechnology in Drug Delivery- Market Characterization analyzes the

market drivers and restrains. This chapter also analyzes opportunities and unmet needs in the

nano-enabled drug delivery market, and product profiles of major marketed products.

· The chapter titled Nanotechnology in Drug Delivery- Trend Analysis analyzes prevailing and

upcoming trends and its effects on the market.

· The chapter titled Nanotechnology in Drug Delivery- Regulatory landscape analyzes regulatory

acceptance and guidelines in different geographical regions. This section also analyzes the

regulatory challenges in nano-enabled drug delivery system market.

· The chapter titled Nanotechnology in Drug Delivery- Pipeline Analysis provides pipeline

analysis for nano-enabled drug delivery. This section includes detailed analysis of the top

companies operating in the market.

· The chapter titled Nanotechnology in Drug Delivery: Strategic Consolidations talks in detail

about the strategic consolidations that have taken place within the nano-enabled drug delivery

market. An analysis of the key licensing agreements is also given with an increasing focus on

geographies.

· The chapter titled Nanotechnology in Drug Delivery: Future Players talks in detail about the

companies, which have strong pipeline candidates.









Nanotechnology in Drug Delivery - Technological Improvements GBIHC043MR / Published DEC 2010

and Novel Approaches to Fulfill High Potential

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© GBI Research. This is a licensed product and is not to be photocopied

3 Application of Nanotechnology in Drug Delivery

Nano-carriers and nano-

engineered drugs are 3.1 Current Applications of Nano-enabled Drug Delivery

widely used in drug

delivery systems 3.1.1 Nano-engineered drugs

3.1.1.1 Nano Crystals

These are single crystalline nano materials which has at least one dimension on the order of

100nm. Nano crystals have a wide range of proven and potential applications in different fields.

Elan Pharma International Ltd. has FDA approval on a NanoCrystal technology in 2000. The

technology improves the bioavailability of Wyeth’s drug sirolimus. The new formulation Rapamune

overcame the drug’s relative insolubility by reducing the particle size to less than 200nm.

3.1.1.2 Nano Suspensions

The poor water solubility of drugs is a major problem for drug formulation which leads to low

bioavailability and erratic absorption. There are a number of formulation approaches to resolve the

problems of low solubility and low bioavailability. The reduction of drug particles into the sub-micron

range leads to a significant increase in the dissolution rate and therefore enhances bioavailability.

Nano suspensions are candidates that can be used to increase the dissolution of drugs that are

poorly soluble in water. Nano suspensions contain submicron colloidal dispersion of

pharmaceutical active ingredient particles in a liquid phase stabilized by surfactants.



Figure 2: Nanotechnology in Drug Delivery, Current Application of Nanotechnology in the

Pharmaceutical Industry, 2010







Nanocrystals- •Carbon & Ceramic

Increased surface Nanostructures

area

•Dendrimers-

Increased drug load







Current

Applications of

Nanotechnology









•Liposomes- Targeted

Nanosuspensions- drug delivery

Increased

bioavailability •Mycelles and

polymeric

Nanoparticles







Source: GBI Research









Nanotechnology in Drug Delivery - Technological Improvements GBIHC043MR / Published DEC 2010

and Novel Approaches to Fulfill High Potential

Page 9

© GBI Research. This is a licensed product and is not to be photocopied

3.1.2 Nano-carriers

3.1.2.1 Carbon and Ceramic Nanostructures

The carbon-based nanostructures include carbon nanotubes, carbon nano particles, and porous

carbons, activated carbon fibers and carbon aerogels. Among these carbon nanotubes are

presently the most attractive carbon nanostructured material being researched in the

pharmaceutical market. The carbon nanotubes are allotropes of carbon with a cylindrical

nanostructure. Ceramic nanostructures are used in biomedical implants.

3.1.2.2 Dendrimers

Dendrimers are monodisperse macromolecules, which fall under a new class of polymeric

materials. These are repeatedly branched and roughly spherical large molecules with very high

symmetry. These unique behaviors make dendrimers a suitable candidate for a wide range of

biomedical and industrial applications. Applications mainly involve conjugation of other chemical

species to the dendrimer surface that can function as detecting agents, imaging agents, and

pharmaceutically active compounds. Dendrimers provide a multivalent system that is exploited in a

number of drug delivery systems.

3.1.2.3 Liposomes

Liposomes are concentric bilayered structures made of amphipathic phospholipids. The Liposomes

are classified as multilamellar (MLV), small unilamellar (SUVs), and large unilamellar (LUV

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