Angiogenesis Modulators: Strategies for Drug Discovery

Angiogenesis Modulators: Strategies for Drug Discovery

Publisher:	D&MD Publications Inc
Year of publication:	2005
Type of publication:	Management report
Publisher's reference (if any):	D&MD9148
Author(s):	Sreten Bogdanovic and Beata Langlands
Approximate page count:	200
Price when published:	$4,950
Remarks: Page numbers, where given, refer to the draft manuscript (which may differ from the published version). The copyright in this report is owned by the publisher, to whom any requests for copies should be addressed. The price shown is for a single copy of the print version. Multiple copies and electronic copies usually have different prices.
ANGIOGENESIS MODULATORS Strategies for Drug Discovery TABLE OF CONTENTS TABLE OF CONTENTS EXECUTIVE SUMMARY CHAPTER 1 INTRODUCTION TO ANGIOGENESIS 1.1 Overview of angiogenesis 1.2 The process of angiogenesis 1.3 Molecules involved in angiogenesis 1.3.1 Growth factors and other angiogenic proteins 1.3.2 Receptor tyrosine kinases 1.3.3 Proteases 1.3.4 Cell adhesion molecules 1.3.5 Endogenous antiangiogenic proteins 1.4 Role of angiogenesis in disease 1.5 Approaches to angiogenesis modulation 1.5.1 Types of drugs under development 1.5.1.1 Small molecule drugs 1.5.1.2 Biopharmaceuticals 1.6 Assays for angiogenesis CHAPTER 2 ANGIOGENESIS IN CANCER 2.1 Overview of cancer 2.2 Cancer therapy 2.2.1 Molecular targeted therapies 2.3 Angiogenesis in cancer 2.3.1 Angiostatic vs angiolytic therapies 2.4 Targets for angiostatic therapies 2.4.1 Growth factors and their receptors 2.4.1.1 VEGF-A 2.4.1.2 VEGFR family 2.4.1.3 EGFR family 2.4.1.4 Other growth factors/receptors 2.4.1.5 Multi-target strategies 2.4.1.6 Applications in hematologic malignancies 2.4.2 ECM-degrading enzymes 2.4.2.1 Matrix metalloproteases 2.4.2.2 Heparanase 2.4.3 Proteases (other than MMPs) 2.4.3.1 ADAMs family 2.4.3.2 uPA 2.4.3.3 Other proteases 2.4.4 Cell adhesion receptors 2.4.4.1 Alpha(v) integrins 2.4.4.2 Other cell adhesion receptors 2.4.5 Agents based on human antiangiogenic factors 2.4.5.1 Endogenous antiangiogenic factors 2.4.5.2 Antiangiogenic gene therapy 2.4.6 Agents of non-human origin 2.4.7 Miscellaneous agents 2.4.7.1 Thalidomide-related drugs 2.4.7.2 Other drugs 2.5 Angiolytic vascular targeting agents 2.5.1 Small molecule VTAs 2.5.1.1 Tubulin-binding agents 2.5.1.2 Other small molecule agents 2.5.2 Ligand-based and other VTAs 2.6 Exploiting angiogenesis for drug delivery CHAPTER 3 ANGIOGENESIS IN CARDIOLOGY 3.1 Overview of cardiovascular disease 3.1.1 Coronary Artery Disease 3.1.1.1 Established treatments 3.1.2 Myocardial infarction 3.1.2.1 Current treatments 3.1.3 Peripheral Vascular Disease 3.1.3.1 Current treatments 3.1.4 Congestive Heart Failure 3.1.4.1 Current treatments 3.2 Angiogenesis in ischemia 3.2.1 Physiological responses to ischemia 3.2.2 Stimulation of angiogenesis in ischemia 3.2.2.1 Transmyocardial revascularization 3.2.2.2 Therapeutic angiogenesis 3.2.2.3 Cell therapy 3.3 Challenge of pathologic angiogenesis 3.3.1 Atherogenesis and atheroscleropathy 3.3.2 Percutaneous coronary interventions 3.3.2.1 Approaches to restenosis prevention 3.4 Angiogenic products in commercial development 3.4.1 Protein and small molecule therapies 3.4.2 Gene therapies 3.4.3 Cell therapies 3.4.3.1 Stem and progenitor cell therapies CHAPTER 4 ANGIOGENESIS IN OPHTHALMOLOGY 4.1 Eye diseases involving neovascularization 4.1.1 Age-related macular degeneration 4.1.2 Diabetic retinopathy 4.1.3 Other disorders 4.2 Angiolytic photodynamic therapy 4.3 Angiogenesis-targeting drugs 4.3.1 Angiostatic drugs 4.3.1.1 Targeting VEGF/VEGFR 4.3.1.2 Miscellaneous targets 4.3.2 Vascular targeting agents CHAPTER 5 OTHER APPLICATIONS OF ANGIOGENIC MODULATION 5.1 Introduction 5.2 Skin diseases 5.2.1 Chronic wounds 5.2.2 Vascular lesions 5.2.2.1 Psoriasis 5.2.2.2 Rosacea 5.2.2.3 Other vascular lesions 5.3 Chronic inflammatory diseases 5.3.1 Rheumatoid arthritis 5.3.2 Periodontitis 5.3.3 Inflammatory bowel disease 5.3.4 Inflammatory lung diseases 5.3.5 Complex regional pain syndrome 5.3.6 Fibrodysplasia Ossificans Progressiva 5.4 Transplant rejection 5.5 Orthodontic applications 5.6 Spinal cord injuries 5.7 Other potential applications 5.7.1 Endometriosis 5.7.2 Obesity 5.7.3 Erectile dysfunction 5.7.4 Benign tumors CHAPTER 6 COMPANY PROFILES 6.0 Introduction 6.1 Abbott Laboratories 6.2 AEterna Zentaris Inc 6.3 Alcon Laboratories Inc 6.4 Amgen Inc 6.5 Angiotech Pharmaceuticals Inc 6.6 Antisoma Plc 6.7 AstraZeneca Plc 6.8 Bayer AG 6.9 Boston Scientific Corporation 6.10 Celgene Corporation 6.11 Collagenex Pharmaceuticals Inc 6.12 Collateral Therapeutics Inc 6.13 Corautus Genetics Inc 6.14 EntreMed Inc 6.15 EyeTech Pharmaceuticals Inc 6.16 Genaera Corporation 6.17 Genentech Inc 6.18 Genzyme Corporation 6.19 GlaxoSmithKline Plc 6.20 Human Genome Sciences 6.21 ImClone Systems Inc 6.22 Merck KGaA 6.23 Merck & Co Inc 6.24 Novartis Pharma AG 6.25 OSI Pharmaceuticals Inc 6.26 OXiGENE Inc 6.27 Pfizer Inc 6.28 Regeneron Pharmaceuticals Inc 6.29 Sirna Therapeutics Inc 6.30 Valentis Inc CHAPTER 7 THE ANGIOGENESIS MODULATION MARKET TO 2009 7.1 Introduction 7.2 Cancer 7.2.1 Overview 7.2.2 Established cancer therapies 7.2.3 The anti-cancer drug market 7.3 Cardiology 7.3.1 Overview 7.3.2 Coronary Artery Disease 7.3.3 Myocardial infarction 7.3.4 Congestive Heart Failure 7.3.5 Established treatments 7.3.6 Cardiology drug market 7.4 Ophthalmology 7.4.1 Overview 7.4.2 Age-related macular degeneration 7.4.3 Diabetic retinopathy 7.4.4 Other eye disorders 7.4.5 Ophthalmology drug market 7.5 Dermatology 7.5.1 Overview 7.5.2 Psoriasis 7.5.3 Benign vascular lesions 7.5.4 Impaired wound healing 7.5.5 Dermatology drug market 7.6 Other indications 7.7 Market Forecasts CHAPTER 8 CONCLUSIONS, TRENDS AND OPPORTUNITIES 8.1 Gap narrows between experimental and clinical data 8.2 VEGF inhibitors lead the way 8.3 Cancer: Opportunities expand 8.3.1 Accelerating approvals 8.3.2 Learning from clinical trials 8.3.3 Optimizing therapies 8.3.4 Towards pharmacogenomic testing 8.3.5 Towards angiogenic profiling 8.3.6 Taking advantage of vascular targeting 8.3.7 Future horizons - cancer prevention? 8.4 AMD: Breakthrough treatments emerge 8.5 Cardiology: Interest peaks despite slow progress 8.6 Other diseases: Largely unexplored opportunities 8.7 Exploiting unexpected angiomodulatory effects APPENDIX 1 GLOSSARY EXECUTIVE SUMMARY After three decades of research in the angiogenesis field, human trials of angiomodulatory compounds are at last beginning to yield commercial products with proven efficacy. Many diverse drugs targeting angiogenesis are in clinical development. This report offers a comprehensive review of targets for angiogenesis modulation, identifies the most promising approaches, and assesses the prospects for angiogenesis modulators in different therapeutic areas. It is not just the developers of angiogenesis-related products who will be affected by developments in this field. In addition to drugs which are being developed as angiomodulatory agents, many drugs which were originally developed for other properties may also have angiomodulatory properties with potential for commercial exploitation. Key areas of opportunity with respect to angiogenesis modulation include major diseases associated with the aging population, such as cancer, age-related macular degeneration, coronary artery disease and peripheral vascular disease. We believe that the potential market for angiogenesis-related therapeutics, if all patients whose problems were susceptible to this approach could be treated accordingly, exceeds $80 billion worldwide. This figure is more than 15% of the global pharmaceutical market. Antiangiogenic strategies aim to halt excessive angiogenesis associated with cancer, vascular eye diseases, vascular skin lesions, chronic inflammatory diseases, and other conditions. Angiogenic strategies aim to stimulate neovascularization in ischemic myocardial and peripheral tissues, and facilitate healing of chronic wounds. We estimate that, neglecting the effects of currency fluctuations, worldwide sales of angiogenesis-related therapeutic products will rise from $2.4 billion in 2004 to $8.7 billion in 2009, a compound annual growth rate (CAGR) of about 30%. Cancer-related products accounted for 72% of sales in 2004 and will account for 53% in 2009, most of the remainder being made up of ophthalmological and anti-inflammatory products. The angiogenesis market is presently dominated by Genentech/Roche, whose Avastin and Herceptin oncology products together generated over $1 billion in 2004 sales, and whose recently introduced Tarceva lung cancer therapeutic could start earning another $500 million per year from 2005. The leading geographical market is the USA, with 45% of worldwide angiogenesis-related sales in 2004, expected to rise slightly to 47% in 2009. The report reveals that over 300 angiogenesis-related therapies are currently under commercial investigation. In addition to recently launched products, it reviews over 230 therapeutic products in development for cancer, and over 70 therapeutic products in development for other indications, primarily in cardiology, ophthalmology, and dermatology. For agents in clinical trials, recent safety and efficacy data are also discussed as they provide some indication as to how successful the particular approach to angiogenesis modulation is likely to be. Angiogenesis and its inhibition represent one of the fastest growing areas of oncology. Studies have demonstrated the profound dependence of tumor growth and metastasis on the generation of new blood vessels. In 1999, the US National Cancer Institute designated the development of antiangiogenic therapies for cancer a national priority, accelerating R&D activity in this area. A significant development in the last few years has been FDA approval of four drugs targeting angiogenic growth factors or their receptors. The breakthrough antiangiogenic oncology drug Avastin achieved sales of $555 million in less than one year on the market since its launch in January 2004. There are also indications that antiangiogenic agents give synergistic effects when combined with current cytotoxic therapies - a strategy which offers significant market opportunities, or when combined with each other - a strategy which provides an important treatment option that does not include conventional cytotoxic chemotherapy. While the process of angiogenesis was initially the main target of angiostatic cancer therapies, more recently the focus of investigations has been shifting to approaches that target and disrupt the established tumor vasculature which are seen as offering many potential advantages. Therapies aimed at diseases of the retina involving neovascularization, such as age-related macular degeneration (AMD) and diabetic retinopathy, look set for high growth in the next couple of years. Recently, the therapeutic approach of targeting angiogenic vessels in neovascular AMD was validated by very successful new product introductions, the angiolytic photodynamic therapy Visudyne and the angiostatic drug Macugen. There has been renewed interest in the development of approaches which seek to restore perfusion and function to chronically ischemic myocardial and peripheral tissues. Early approaches to therapeutic angiogenesis revolved around single angiogenic factor application and gene therapy, and despite setbacks, therapeutic angiogenesis remains a promising avenue. A relatively new approach to stimulation of myocardial neovasculatization, stem cell therapy, is currently generating intense interest. In the case of chronic wounds, several recently approved products, including cell therapy products, work partly through stimulation of angiogenesis, and several more are in development. Although most of the preclinical and clinical programs in angiogenesis modulation are currently concentrated in the areas of oncology, cardiology, and ophthalmology, these studies are paving the way for clinical applications in miscellaneous other diseases. Already antiangiogenic drugs are making their presence felt in the clinic as new treatment modalities for skin diseases such as psoriasis and rosacea, and chronic inflammatory diseases such as periodontitis and rheumatoid arthritis.

Publisher:

D&MD Publications Inc

Year of publication:

2005

Type of publication:

Management report

Publisher's reference (if any):

D&MD9148

Author(s):

Sreten Bogdanovic and Beata Langlands

Approximate page count:

200

Price when published:

$4,950

Remarks:

Page numbers, where given, refer to the draft manuscript (which may differ from the published version).
The copyright in this report is owned by the publisher, to whom any requests for copies should be addressed.
The price shown is for a single copy of the print version. Multiple copies and electronic copies usually have different prices.

                              ANGIOGENESIS MODULATORS
                           Strategies for Drug Discovery

                                 TABLE OF CONTENTS

         TABLE OF CONTENTS

         EXECUTIVE SUMMARY

         CHAPTER 1 INTRODUCTION TO ANGIOGENESIS

           1.1 Overview of angiogenesis
           1.2 The process of angiogenesis
           1.3 Molecules involved in angiogenesis
              1.3.1 Growth factors and other angiogenic proteins
              1.3.2 Receptor tyrosine kinases
              1.3.3 Proteases
              1.3.4 Cell adhesion molecules
              1.3.5 Endogenous antiangiogenic proteins
           1.4 Role of angiogenesis in disease
           1.5 Approaches to angiogenesis modulation
              1.5.1 Types of drugs under development
                1.5.1.1 Small molecule drugs
                1.5.1.2 Biopharmaceuticals
           1.6 Assays for angiogenesis

         CHAPTER 2 ANGIOGENESIS IN CANCER

           2.1 Overview of cancer
           2.2 Cancer therapy
              2.2.1 Molecular targeted therapies
           2.3 Angiogenesis in cancer
              2.3.1 Angiostatic vs angiolytic therapies
           2.4 Targets for angiostatic therapies
              2.4.1 Growth factors and their receptors
                2.4.1.1 VEGF-A
                2.4.1.2 VEGFR family
                2.4.1.3 EGFR family
                2.4.1.4 Other growth factors/receptors
                2.4.1.5 Multi-target strategies
                2.4.1.6 Applications in hematologic malignancies
              2.4.2 ECM-degrading enzymes
                2.4.2.1 Matrix metalloproteases
                2.4.2.2 Heparanase
              2.4.3 Proteases (other than MMPs)
                2.4.3.1 ADAMs family
                2.4.3.2 uPA
                2.4.3.3 Other proteases
              2.4.4 Cell adhesion receptors
                2.4.4.1 Alpha(v) integrins
                2.4.4.2 Other cell adhesion receptors
              2.4.5 Agents based on human antiangiogenic factors
                2.4.5.1 Endogenous antiangiogenic factors
                2.4.5.2 Antiangiogenic gene therapy
              2.4.6 Agents of non-human origin
              2.4.7 Miscellaneous agents
                2.4.7.1 Thalidomide-related drugs
                2.4.7.2 Other drugs
           2.5 Angiolytic vascular targeting agents
              2.5.1 Small molecule VTAs
                2.5.1.1 Tubulin-binding agents
                2.5.1.2 Other small molecule agents
              2.5.2 Ligand-based and other VTAs
           2.6 Exploiting angiogenesis for drug delivery

         CHAPTER 3 ANGIOGENESIS IN CARDIOLOGY

           3.1 Overview of cardiovascular disease
              3.1.1 Coronary Artery Disease
                3.1.1.1 Established treatments
              3.1.2 Myocardial infarction
                3.1.2.1 Current treatments
              3.1.3 Peripheral Vascular Disease
                3.1.3.1 Current treatments
              3.1.4 Congestive Heart Failure
                3.1.4.1 Current treatments
           3.2 Angiogenesis in ischemia
              3.2.1 Physiological responses to ischemia
              3.2.2 Stimulation of angiogenesis in ischemia
                3.2.2.1 Transmyocardial revascularization
                3.2.2.2 Therapeutic angiogenesis
                3.2.2.3 Cell therapy
           3.3 Challenge of pathologic angiogenesis
              3.3.1 Atherogenesis and atheroscleropathy
              3.3.2 Percutaneous coronary interventions
                3.3.2.1 Approaches to restenosis prevention
           3.4 Angiogenic products in commercial development
              3.4.1 Protein and small molecule therapies
              3.4.2 Gene therapies
              3.4.3 Cell therapies
                3.4.3.1 Stem and progenitor cell therapies

         CHAPTER 4 ANGIOGENESIS IN OPHTHALMOLOGY

           4.1  Eye diseases involving neovascularization
              4.1.1 Age-related macular degeneration
              4.1.2 Diabetic retinopathy
              4.1.3 Other disorders
           4.2 Angiolytic photodynamic therapy
           4.3 Angiogenesis-targeting drugs
              4.3.1 Angiostatic drugs
                4.3.1.1 Targeting VEGF/VEGFR
                4.3.1.2 Miscellaneous targets
              4.3.2 Vascular targeting agents

         CHAPTER 5 OTHER APPLICATIONS OF ANGIOGENIC MODULATION

           5.1  Introduction
           5.2  Skin diseases
              5.2.1 Chronic wounds
              5.2.2 Vascular lesions
                5.2.2.1 Psoriasis
                5.2.2.2 Rosacea
                5.2.2.3 Other vascular lesions
           5.3 Chronic inflammatory diseases
              5.3.1 Rheumatoid arthritis
              5.3.2 Periodontitis
              5.3.3 Inflammatory bowel disease
              5.3.4 Inflammatory lung diseases
              5.3.5 Complex regional pain syndrome
              5.3.6 Fibrodysplasia Ossificans Progressiva
           5.4 Transplant rejection
           5.5 Orthodontic applications
           5.6 Spinal cord injuries
           5.7 Other potential applications
              5.7.1 Endometriosis
              5.7.2 Obesity
              5.7.3 Erectile dysfunction
              5.7.4 Benign tumors

         CHAPTER 6 COMPANY PROFILES

           6.0 Introduction
           6.1 Abbott Laboratories
           6.2 AEterna Zentaris Inc
           6.3 Alcon Laboratories Inc
           6.4 Amgen Inc
           6.5 Angiotech Pharmaceuticals Inc
           6.6 Antisoma Plc
           6.7 AstraZeneca Plc
           6.8 Bayer AG
           6.9 Boston Scientific Corporation
           6.10 Celgene Corporation
           6.11 Collagenex Pharmaceuticals Inc
           6.12 Collateral Therapeutics Inc
           6.13 Corautus Genetics Inc
           6.14 EntreMed Inc
           6.15 EyeTech Pharmaceuticals Inc
           6.16 Genaera Corporation
           6.17 Genentech Inc
           6.18 Genzyme Corporation
           6.19 GlaxoSmithKline Plc
           6.20 Human Genome Sciences
           6.21 ImClone Systems Inc
           6.22 Merck KGaA
           6.23 Merck & Co Inc
           6.24 Novartis Pharma AG
           6.25 OSI Pharmaceuticals Inc
           6.26 OXiGENE Inc
           6.27 Pfizer Inc
           6.28 Regeneron Pharmaceuticals Inc
           6.29 Sirna Therapeutics Inc
           6.30 Valentis Inc

         CHAPTER 7  THE ANGIOGENESIS MODULATION MARKET TO 2009

            7.1  Introduction
            7.2  Cancer
               7.2.1  Overview
            7.2.2  Established cancer therapies
               7.2.3  The anti-cancer drug market
            7.3  Cardiology
               7.3.1  Overview
               7.3.2  Coronary Artery Disease
               7.3.3  Myocardial infarction
               7.3.4  Congestive Heart Failure
               7.3.5  Established treatments
               7.3.6  Cardiology drug market
            7.4  Ophthalmology
               7.4.1  Overview
               7.4.2  Age-related macular degeneration
               7.4.3  Diabetic retinopathy
               7.4.4  Other eye disorders
               7.4.5  Ophthalmology drug market
            7.5  Dermatology
               7.5.1  Overview
               7.5.2  Psoriasis
            7.5.3  Benign vascular lesions
               7.5.4  Impaired wound healing
               7.5.5  Dermatology drug market
            7.6  Other indications
            7.7  Market Forecasts

         CHAPTER 8 CONCLUSIONS, TRENDS AND OPPORTUNITIES

           8.1 Gap narrows between experimental and clinical data
           8.2 VEGF inhibitors lead the way
           8.3 Cancer: Opportunities expand
              8.3.1 Accelerating approvals
              8.3.2 Learning from clinical trials
              8.3.3 Optimizing therapies
              8.3.4 Towards pharmacogenomic testing
              8.3.5 Towards angiogenic profiling
              8.3.6 Taking advantage of vascular targeting
              8.3.7 Future horizons - cancer prevention?
           8.4 AMD: Breakthrough treatments emerge
           8.5 Cardiology: Interest peaks despite slow progress
           8.6 Other diseases: Largely unexplored opportunities
           8.7 Exploiting unexpected angiomodulatory effects

         APPENDIX 1 GLOSSARY

EXECUTIVE SUMMARY
After three decades of research in the angiogenesis field, human trials of angiomodulatory compounds are at last beginning to yield commercial products with proven efficacy. Many diverse drugs targeting angiogenesis are in clinical development. This report offers a comprehensive review of targets for angiogenesis modulation, identifies the most promising approaches, and assesses the prospects for angiogenesis modulators in different therapeutic areas.
It is not just the developers of angiogenesis-related products who will be affected by developments in this field. In addition to drugs which are being developed as angiomodulatory agents, many drugs which were originally developed for other properties may also have angiomodulatory properties with potential for commercial exploitation.
Key areas of opportunity with respect to angiogenesis modulation include major diseases associated with the aging population, such as cancer, age-related macular degeneration, coronary artery disease and peripheral vascular disease. We believe that the potential market for angiogenesis-related therapeutics, if all patients whose problems were susceptible to this approach could be treated accordingly, exceeds $80 billion worldwide. This figure is more than 15% of the global pharmaceutical market. Antiangiogenic strategies aim to halt excessive angiogenesis associated with cancer, vascular eye diseases, vascular skin lesions, chronic inflammatory diseases, and other conditions. Angiogenic strategies aim to stimulate neovascularization in ischemic myocardial and peripheral tissues, and facilitate healing of chronic wounds.
We estimate that, neglecting the effects of currency fluctuations, worldwide sales of angiogenesis-related therapeutic products will rise from $2.4 billion in 2004 to $8.7 billion in 2009, a compound annual growth rate (CAGR) of about 30%. Cancer-related products accounted for 72% of sales in 2004 and will account for 53% in 2009, most of the remainder being made up of ophthalmological and anti-inflammatory products. The angiogenesis market is presently dominated by Genentech/Roche, whose Avastin and Herceptin oncology products together generated over $1 billion in 2004 sales, and whose recently introduced Tarceva lung cancer therapeutic could start earning another $500 million per year from 2005. The leading geographical market is the USA, with 45% of worldwide angiogenesis-related sales in 2004, expected to rise slightly to 47% in 2009.
The report reveals that over 300 angiogenesis-related therapies are currently under commercial investigation. In addition to recently launched products, it reviews over 230 therapeutic products in development for cancer, and over 70 therapeutic products in development for other indications, primarily in cardiology, ophthalmology, and dermatology. For agents in clinical trials, recent safety and efficacy data are also discussed as they provide some indication as to how successful the particular approach to angiogenesis modulation is likely to be.
Angiogenesis and its inhibition represent one of the fastest growing areas of oncology. Studies have demonstrated the profound dependence of tumor growth and metastasis on the generation of new blood vessels. In 1999, the US National Cancer Institute designated the development of antiangiogenic therapies for cancer a national priority, accelerating R&D activity in this area. A significant development in the last few years has been FDA approval of four drugs targeting angiogenic growth factors or their receptors. The breakthrough antiangiogenic oncology drug Avastin achieved sales of $555 million in less than one year on the market since its launch in January 2004.
There are also indications that antiangiogenic agents give synergistic effects when combined with current cytotoxic therapies - a strategy which offers significant market opportunities, or when combined with each other - a strategy which provides an important treatment option that does not include conventional cytotoxic chemotherapy. While the process of angiogenesis was initially the main target of angiostatic cancer therapies, more recently the focus of investigations has been shifting to approaches that target and disrupt the established tumor vasculature which are seen as offering many potential advantages.
Therapies aimed at diseases of the retina involving neovascularization, such as age-related macular degeneration (AMD) and diabetic retinopathy, look set for high growth in the next couple of years. Recently, the therapeutic approach of targeting angiogenic vessels in neovascular AMD was validated by very successful new product introductions, the angiolytic photodynamic therapy Visudyne and the angiostatic drug Macugen.
There has been renewed interest in the development of approaches which seek to restore perfusion and function to chronically ischemic myocardial and peripheral tissues. Early approaches to therapeutic angiogenesis revolved around single angiogenic factor application and gene therapy, and despite setbacks, therapeutic angiogenesis remains a promising avenue. A relatively new approach to stimulation of myocardial neovasculatization, stem cell therapy, is currently generating intense interest. In the case of chronic wounds, several recently approved products, including cell therapy products, work partly through stimulation of angiogenesis, and several more are in development.
Although most of the preclinical and clinical programs in angiogenesis modulation are currently concentrated in the areas of oncology, cardiology, and ophthalmology, these studies are paving the way for clinical applications in miscellaneous other diseases. Already antiangiogenic drugs are making their presence felt in the clinic as new treatment modalities for skin diseases such as psoriasis and rosacea, and chronic inflammatory diseases such as periodontitis and rheumatoid arthritis.